Pneumonia, Viral
Conditions
Keywords
Covid-19, SARS-CoV-2, Pneumonia, Severe pneumonia
Brief summary
The study objective is to assess Efficacy and safety of Reparixin treatment as compared to placebo (both on top of standard treatment) in adult patients with severe COVID-19 pneumonia.
Detailed description
This is a phase 3 clinical trial designed as a randomized, double-blind, placebo-controlled, multicentre study to evaluate the efficacy and safety of Reparixin in hospitalized adult patients with severe COVID-19 pneumonia. Patients will be screened for the participation in the study and eventually randomized based on an unbalanced randomization scheme (2:1) to Reparixin oral tablets (2 x 600 mg TID) for up to 21 days or to placebo. An unequal randomization is justified by the need to gain experience and more safety data with the investigated treatment and by an expected better acceptability of the trial by patients. The placebo control arm is justified by the unavailability of a well-defined standard of care for subjects with COVID-19 pneumonia who are candidates for this study. All patient will receive the standard supportive care based on the patient's clinical need. Follow-up information on the patient's clinical condition will be collected until day 90.
Interventions
DRUGReparixin
2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily).
OTHERPlacebo
Matched placebo, i.e. 2 tablets for the total of three daily administrations (6 tablets daily).
Sponsors
Dompé Farmaceutici S.p.A
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
subjects will be randomized with a 2:1 randomization ratio
Eligibility
Sex/Gender
ALL
Age
18 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Age 18 to 90, male and female subject of any race 2. Reverse transcriptase Polymerase Chain Reaction (rt-PCR)-confirmed COVID-19 infection based on a nasal / oropharyngeal swab within 10 days before randomization 3. At least one of the following: 1) Respiratory distress with tachypnea (RR ≥ 24 breaths/min without oxygen); 2) Partial arterial oxygen pressure (PaO2) / Fraction of inspiration O2 (FiO2), P/F \>100 and \<300 mmHg (1mmHg = 0.133kPa), 3) SpO2 ≤ 94% while breathing ambient air. Calculation through validated Sat/FiO2 scales is allowed. P/F value of reference if the last available before the signature of consent. 4. Need of supplemental oxygen (i.e. new use of supplemental oxygen, or increased oxygen requirement if on chronic oxygen) requiring low- or high-flow oxygen or non-invasive mechanical ventilation (7-point WHO-OS category 4 or 5). 5. Radiological chest imaging (X-rays, CT scan) confirms lung involvement and inflammation.
Exclusion criteria
1. Cannot obtain informed consent. 2. Hepatic dysfunction with Child Pugh score B or C, or ALT or AST\> 5 times the upper limit. 3. Renal dysfunction with estimated glomerular filtration rate (MDRD) \< 50 mL/min/1.73 m2 or patient receiving continuous renal replacement therapy, hemodialysis, or peritoneal dialysis. 4. Bacterial sepsis (besides COVID-19 sepsis). 5. Known congenital or acquired immune deficiency. 6. Positive or missing pregnancy test before first drug intake or day 1; pregnant or lactating women; women of childbearing potential and fertile men who do not agree to use at least one primary form of contraception for the duration of the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Alive and Free of Respiratory Failure at Day 28 | At day 28 | The event variable is defined as the proportion of patients alive and free of respiratory failure at Day 28. This means no need of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) or admission to intensive care unit (ICU) linked to worsening of respiratory parameters compared to baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Mortality Rates up to Day 28 | Up to Day 28 | This key secondary efficacy endpoint describes number and proportion along with the 95% CI (Clopper-Pearson's formula) of patients who died up to Day 28. |
| Incidence of ICU Admission Until Day 28 | Until day 28 | This is a key secondary efficacy endpoint. Admissions to Intensive Care Unit (ICU) had to be considered only in presence of significant worsening of respiratory status. This condition was objectively identified by means of a decrease of PaO2/FiO2 ratio of at least 40% from the baseline value or by a worsening of Investigator's Interpretation. |
| Time to Recovery (Category 1 - 2 - 3 of the 7-point WHO Ordinal Scale of Clinical Improvement (WHO-OS)) Until Day 28 | Until Day 28 | This is a key secondary efficacy endpoint. The event recovery was considered as such, if the patient has scored category 1, 2 or 3 from the 7-point WHO Ordinal Scale of clinical improvement (WHO-OS), otherwise it will be considered free of event. Category 1: not hospitalized, with resumption of normal activities; 2: not hospitalized, but unable to resume normal activities; 3: hospitalized, not requiring supplemental oxygen; \[4: hospitalized, requiring supplemental oxygen; 5: hospitalized, requiring high-flow oxygen therapy, non-invasive mechanical ventilation, or both; 6: hospitalized, requiring ECMO, invasive mechanical ventilation, or both; 7: death\]. The lower the category, the better the outcome. |
| Proportion of Patients Alive and Free of Respiratory Failure at Fixed Timepoints | At Days 3, 7(±1),14(±2), 21(±2) and 90(±2) after randomization (randomization = day 1) | The event variable is defined as the proportion of patients alive and free of respiratory failure at fixed timepoints. This means no need of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) or admission to intensive care unit (ICU) linked to worsening of respiratory parameters compared to baseline. Admissions to ICU had to be considered only in presence of significant worsening of respiratory status. This condition was objectively identified by means of a decrease of PaO2/FiO2 ratio of at least 40% from the baseline value or by a worsening of Investigator's Interpretation. |
| Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints | At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months) | Changes from baseline in clinical severity score are analyzed based on the 7-point WHO-OS. The 7-point WHO Ordinal Scale of clinical improvement (WHO-OS), comprises the following categories: 1: not hospitalized, with resumption of normal activities; 2: not hospitalized, but unable to resume normal activities; 3: hospitalized, not requiring supplemental oxygen; 4: hospitalized, requiring supplemental oxygen; 5: hospitalized, requiring high-flow oxygen therapy, non-invasive mechanical ventilation, or both; 6: hospitalized, requiring ECMO, invasive mechanical ventilation, or both; 7: death. |
| Number of Patients With Clinical Improvement 1 up to Day 28 (Decline of 1 Category in the 7-point WHO-OS) | Day 1 (baseline), Days 3, 7, 14, 21, 28. | Clinical improvement 1 is defined as the decline of 1 category in the 7-point WHO-OS up to Date 28. The clinical improvement 1 up to Day 28 was analyzed as described for time to recovery: an event was considered as such, if patient declined of at least 1 category in the 7-point WHO-OS respect to the baseline, otherwise it was be considered free of event. |
| Percentage of Participants With Clinical Improvement 1 up to Day 28 | At day 28 | Clinical improvement 1 up to Date 28 for this outcome is expressed as cumulative incidence function (CIF in %). CIF allows for estimation of the occurrence of an event while taking into account the following competing risks: death, reasons for discontinuation for Adverse events and patient transferred to another institution. Estimates are calculated using a nonparametric method. The null hypothesis is that the cumulative incidence functions are identical across treatment groups. |
| Number of Patients With Clinical Improvement 2 up to Day 28 (Decline of 2 Categories in the 7-point WHO-OS) | Day 1 (baseline), Days 3, 7, 14, 21, 28 | Clinical improvement 2 is defined as the decline of 2 categories in the 7-point WHO-OS) up to Date 28. Clinical improvement 2 up to Date 28 was analyzed as described for time to recovery. An event was considered as such, if patient declined of at least 2 categories in the 7-point WHO-OS respect to the baseline, otherwise it was considered free of event. |
| Percentage of Participants With Clinical Improvement 2 up to Day 28 | At Day 28 | Clinical improvement 2 up to Day 28 is defined as cumulative incidence function (CIF, in %). CIF allows for estimation of the occurrence of an event while taking into account the following competing risks: death, reasons for discontinuation for Adverse events and patient transferred to another institution. Estimates are calculated using a nonparametric method. The null hypothesis is that the cumulative incidence functions are identical across treatment groups. |
| Time to Discharge From Hospital up to Day 28 | Day 1 (baseline), Days 3, 7, 14, 21, 28 | Time to discharge from hospital up to Day 28 is analyzed as described for time to recovery. |
| Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months) | Clinical status is analyzed based on the 7-point WHO-OS. The 7-point WHO Ordinal Scale of clinical improvement (WHO-OS), comprises the following categories: 1: not hospitalized, with resumption of normal activities; 2: not hospitalized, but unable to resume normal activities; 3: hospitalized, not requiring supplemental oxygen; 4: hospitalized, requiring supplemental oxygen; 5: hospitalized, requiring high-flow oxygen therapy, non-invasive mechanical ventilation, or both; 6: hospitalized, requiring ECMO, invasive mechanical ventilation, or both; 7: death. The higher the score, the worse the outcome. |
| The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months) | The number of patients with Dyspnea severity Likert scale by score and treatment group is calculated for each time point. Likert scale: grading the current experience of breathing discomfort compared to baseline (randomization) status (from -3 to 3) where: -1 = minimally worse; -2 = moderately worse; -3 = markedly worse; 0 = no change; 1 = minimally better; 2 = moderately better; 3 = markedly better More negative the score, the worse the outcome. |
| Proportion of Patients Alive and Free of Respiratory Failure at Day 60 | At day 60 | This key secondary efficacy endpoint of the study is defined as the proportion of patients alive and free of respiratory failure at Day 60, i.e. with no need of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) or admission to intensive care unit (ICU) linked to worsening of respiratory parameters compared to baseline. |
| Change From Baseline in Dyspnea Severity (VAS Scale) at Fixed Timepoints | At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months) | The pain VAS is a unidimensional measure of pain intensity, used to record patients' pain progression, or compare pain severity between paints with similar conditions.The VAS scale is from 0 to 100. The number 0 means the worst breathing the patient has ever felt, and the number 100 means the best the patient has ever felt. |
| Duration of Supplemental Oxygen Treatment up to Day 28 | From baseline up to day 28 | This endpoint is expressed as: * The number and proportion along with the 95% CI (Clopper-Pearson's formula) of patients using supplemental oxygen treatment by treatment group; * The Cumulative duration of supplemental oxygen treatment in days analyzed by means of descriptive statistics by treatment. This latter is reported in the system. |
| Number of Patients Requiring Invasive Mechanical Ventilation Use, or ECMO up to Day 28 and up to Day 60 | day 28 and Day 60 | Invasive mechanical ventilation is defined as the delivery of positive pressure to the lungs via an endotracheal or tracheostomy tube. During mechanical ventilation, a predetermined mixture of air (ie, oxygen and other gases) is forced into the central airways and then flows into the alveoli. |
| Duration of Non-invasive Mechanical Ventilation up to Day 60 | From baseline up to day 60 | Non-invasive ventilation (NIV) is the delivery of oxygen (ventilation support) via a face mask and therefore eliminating the need of an endotracheal airway. NIV achieves comparative physiological benefits to conventional mechanical ventilation by reducing the work of breathing and improving gas exchange. |
| Duration of Invasive Mechanical Ventilation, or ECMO up to Day 60 | Up to day 60 | Invasive mechanical ventilation is defined as the delivery of positive pressure to the lungs via an endotracheal or tracheostomy tube. During mechanical ventilation, a predetermined mixture of air (ie, oxygen and other gases) is forced into the central airways and then flows into the alveoli. |
| Duration of ICU Admission up to Day 60 | Up to day 60 | Admission to intensive care unit or ICU is linked to worsening of respiratory parameters compared to baseline. |
| Change From Baseline to Fixed Timepoints of Partial Pressure of Oxygen (PaO2) | At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months) | PaO2-the oxygen pressure in arterial blood. The PaO2 reflects how well oxygen is able to move from the lungs to the blood. It is often altered by severe illnesses, with the PaO2 test results used to guide treatment. |
| Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio. | At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months) | The PaO2/FiO2 ratio is used to determine the severity of lung injury in mechanically ventilated patients. A normal P/F Ratio is ≥ 400 and equivalent to a PaO2 ≥ 80 mmHg on room air. Low values of the PaO2/FIO2 ratio may be due to pathological conditions, primarily those of a respiratory nature (atelectasis, ARDS, acute pulmonary edema, pneumonia, etc.), as well as to alterations in hemodynamic status (cardiogenic shock, septic shock, etc.), or even both. |
| Change From Baseline to Fixed Endpoints in High-Sensitivity C Reactive Protein (Hs-CRP) | At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months) | The high-sensitivity C-reactive protein (hs-CRP) test is more sensitive than the standard CRP test measuring slight increases in CRP levels even when within the normal range. Because of this greater sensitivity, the hs-CRP test can help determine your risk of cardiovascular disease (CVD). |
| Mortality Rates up to Days 60 and 90 | up to Days 60 and 90 | Mortality rate, or death rate, is a measure of the number of deaths (in general, or due to a specific cause) in a particular population, scaled to the size of that population, per unit of time. The death event variable is defined as the proportion of patients died up to Day 90. |
| Freedom From (Time to) Death or Respiratory Failure up to Day 90 | at baseline, day 3, day 7, day 14, day 21, day 28, day 60, day 90 | Freedom from (time to) death or respiratory failure (need of invasive mechanical ventilation or ECMO or admission to ICU linked to worsening of respiratory parameters compared to baseline) at baseline, day 3, day 7, day 14, day 21, day 28, day 60, day 90 was performed using the same Kaplan-Meier analysis and the one-sided log-rank test that were used to test for differences between groups. |
| Number of Subjects Who Exhibited at Least 1 TEAE, at Least 1 Severe TEAE, at Least 1 Serious TEAE, at Least 1 Non-serious TEAE, at Least 1 ADR, at Least 1 Serious ADR, at Least 1 TEAE Leading to Discontinuation of IMP, Etc. | Throughout the study, till Day 90 (= end of the follow-up period). | AE= An adverse event is any untoward or unfavorable medical occurrence in a human. subject, including any abnormal sign (for example, abnormal physical exam or. laboratory finding), symptom, or disease, temporally associated with the subject's. serious AE=a SAE iA serious adverse event (SAE) in human drug trials is defined as any untoward medical occurrence that at any dose results in death Is life-threatening Requires inpatient hospitalization or causes prolongation of existing hospitalization Results in persistent or significant disability/incapacity May have caused a congenital anomaly/birth defect Requires intervention to prevent permanent impairment or damage. The term life-threatening in the definition of serious refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe. Do note that starting from this point the safety endpoint is analysed. |
| Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2). | At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months) | Peripheral oxygen saturation (SpO2) monitoring by pulse oximetry is used to estimate the oxygen saturation of arterial blood (SaO2) and provides vital information about a patient's cardiorespiratory function. |
Countries
Italy, United States
Participant flow
Recruitment details
The eligible patient population consisted of hospitalized adult patients with reverse transcriptase polymerase chain reaction (rt-PCR)-confirmed severe COVID-19. Patients were considered to have severe disease in the presence of respiratory distress and requiring supplemental oxygen. No gender and/or ethnicity restrictions applied.
Pre-assignment details
A total of 287 patients were enrolled and 279 of them were randomized to the assigned treatment group (8 patients were not randomized): 185 patients were randomized to receive Reparixin and 94 patients were randomized to receive placebo (N=279). Nine of these latter were randomized but not treated (3 Reparixin and 6 Placebo). Hence, the number of treated patients (starters) was 270 (182 in Reparixin and 88 in placebo).
Participants by arm
| Arm | Count |
|---|---|
| Reparixin Reparixin oral tablets, 1200 mg three times daily (TID) (2 tablets 600 mg each, TID) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care
Reparixin: 2 tablets of Reparixin (600 mg each), for the total of three daily administrations (6 tablets daily).
Please note that patients randomized to Reparixin were 185, but the ones receiving at least one dose of IMP were 182. Three patients, hence, in this group were excluded from the primary FAS analysis of efficacy and from the safety analysis. | 182 |
| Placebo Placebo, 2 tablets TID (identical to Reparixin tablets) for up to 21 days or until decision of discharge from the hospital, on top of standard supportive care.
For each administration, two tablets of Reparixin (600 mg each) or placebo were taken, for the total of three daily administrations (6 tablets daily). It was advisable to take the tablets with a glass of water to facilitate swallowing.
Please note that patients randomized to placebo were 94, but the ones receiving it were 88. Six patients in this group, hence, were excluded from the primary FAS analysis of efficacy and from the safety analysis. | 88 |
| Total | 270 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 12 | 7 |
| Overall Study | Day 60 visit not performed by mistake | 0 | 4 |
| Overall Study | Lost to Follow-up | 10 | 1 |
| Overall Study | Other | 5 | 0 |
| Overall Study | Patient transferred in another department | 0 | 2 |
| Overall Study | Physician Decision | 1 | 1 |
| Overall Study | Withdrawal by Subject | 7 | 3 |
Baseline characteristics
| Characteristic | Reparixin | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 70 Participants | 30 Participants | 100 Participants |
| Age, Categorical Between 18 and 65 years | 112 Participants | 58 Participants | 170 Participants |
| Age, Continuous | 61.3 years STANDARD_DEVIATION 11.8 | 60.0 years STANDARD_DEVIATION 12 | 60.9 years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 50 Participants | 22 Participants | 72 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 132 Participants | 66 Participants | 198 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Region of Enrollment Italy | 182 participants | 88 participants | 270 participants |
| Sex: Female, Male Female | 50 Participants | 25 Participants | 75 Participants |
| Sex: Female, Male Male | 132 Participants | 63 Participants | 195 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 11 / 182 | 7 / 88 |
| other Total, other adverse events | 75 / 182 | 42 / 88 |
| serious Total, serious adverse events | 20 / 182 | 13 / 88 |
Outcome results
Primary
Proportion of Patients Alive and Free of Respiratory Failure at Day 28
The event variable is defined as the proportion of patients alive and free of respiratory failure at Day 28. This means no need of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) or admission to intensive care unit (ICU) linked to worsening of respiratory parameters compared to baseline.
Time frame: At day 28
Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reparixin | Proportion of Patients Alive and Free of Respiratory Failure at Day 28 | 152 participants |
| Placebo | Proportion of Patients Alive and Free of Respiratory Failure at Day 28 | 71 participants |
Comparison: Analysis is based on logistic regression model with Multiple Imputation under missing not at random using retrieve dropouts with proportion of patients alive and free of respiratory failure at Day 28 as dependent variable, treatment, age group, gender and presence of concomitant disease at baseline as qualitative independent variables. Site is considered as random effects that vary randomly among patients.p-value: 0.21695% CI: [0.752, 3.514]Two-sided regression, Logistic
Secondary
Change From Baseline in Dyspnea Severity (VAS Scale) at Fixed Timepoints
The pain VAS is a unidimensional measure of pain intensity, used to record patients' pain progression, or compare pain severity between paints with similar conditions.The VAS scale is from 0 to 100. The number 0 means the worst breathing the patient has ever felt, and the number 100 means the best the patient has ever felt.
Time frame: At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months)
Population: FAS Full Analysis Set: set which consisted of all randomized subjects who received at least one dose of the IMP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reparixin | Change From Baseline in Dyspnea Severity (VAS Scale) at Fixed Timepoints | day 14(+/-2) | 12.7 score on a scale | Standard Deviation 38.5 |
| Reparixin | Change From Baseline in Dyspnea Severity (VAS Scale) at Fixed Timepoints | day 28 (+/-2) | 31.1 score on a scale | Standard Deviation 20.3 |
| Reparixin | Change From Baseline in Dyspnea Severity (VAS Scale) at Fixed Timepoints | day 7 (+/-1) | 8.3 score on a scale | Standard Deviation 31.1 |
| Reparixin | Change From Baseline in Dyspnea Severity (VAS Scale) at Fixed Timepoints | Hospital discharge | 12.3 score on a scale | Standard Deviation 44 |
| Reparixin | Change From Baseline in Dyspnea Severity (VAS Scale) at Fixed Timepoints | day 21 (+/-2) | 16.0 score on a scale | Standard Deviation 39.5 |
| Reparixin | Change From Baseline in Dyspnea Severity (VAS Scale) at Fixed Timepoints | EoT | 17.1 score on a scale | Standard Deviation 32.6 |
| Reparixin | Change From Baseline in Dyspnea Severity (VAS Scale) at Fixed Timepoints | day 3 | 6.4 score on a scale | Standard Deviation 25.3 |
| Placebo | Change From Baseline in Dyspnea Severity (VAS Scale) at Fixed Timepoints | EoT | 8.6 score on a scale | Standard Deviation 37.8 |
| Placebo | Change From Baseline in Dyspnea Severity (VAS Scale) at Fixed Timepoints | day 3 | 2.2 score on a scale | Standard Deviation 20.6 |
| Placebo | Change From Baseline in Dyspnea Severity (VAS Scale) at Fixed Timepoints | day 7 (+/-1) | -0.2 score on a scale | Standard Deviation 31.1 |
| Placebo | Change From Baseline in Dyspnea Severity (VAS Scale) at Fixed Timepoints | day 14(+/-2) | 6.6 score on a scale | Standard Deviation 37.4 |
| Placebo | Change From Baseline in Dyspnea Severity (VAS Scale) at Fixed Timepoints | day 21 (+/-2) | 32.5 score on a scale | Standard Deviation 14.3 |
| Placebo | Change From Baseline in Dyspnea Severity (VAS Scale) at Fixed Timepoints | day 28 (+/-2) | 40.7 score on a scale | Standard Deviation 8.3 |
| Placebo | Change From Baseline in Dyspnea Severity (VAS Scale) at Fixed Timepoints | Hospital discharge | 10.2 score on a scale | Standard Deviation 41.5 |
Comparison: at day 3 - Please note that the number of subjects in this analysis is not 270, but it is 157p-value: 0.399Wilcoxon (Mann-Whitney)
Comparison: at day 7 - Please note that the number of subjects in this analysis is not 270, but it is 139p-value: 0.07Wilcoxon (Mann-Whitney)
Comparison: at day 14 - Please note that the number of subjects in this analysis is not 270, but it is 73p-value: 0.4Wilcoxon (Mann-Whitney)
Comparison: at day 21 - Please note that the number of subjects in this analysis is not 270, but it is 23p-value: 0.517Wilcoxon (Mann-Whitney)
Comparison: at day 28 - Please note that the number of subjects in this analysis is not 270, but it is 17p-value: 0.445Wilcoxon (Mann-Whitney)
Comparison: at EoT - Please note that the number of subjects in this analysis is not 270, but it is 113p-value: 0.324Wilcoxon (Mann-Whitney)
Comparison: at Hospital discharge - Please note that the number of subjects in this analysis is not 270, but it is 67.p-value: 0.752Wilcoxon (Mann-Whitney)
Secondary
Change From Baseline to Fixed Endpoints in High-Sensitivity C Reactive Protein (Hs-CRP)
The high-sensitivity C-reactive protein (hs-CRP) test is more sensitive than the standard CRP test measuring slight increases in CRP levels even when within the normal range. Because of this greater sensitivity, the hs-CRP test can help determine your risk of cardiovascular disease (CVD).
Time frame: At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months)
Population: FAS population is used in this table. Discrepancies between the total number of patients in the FAS and patients actually analyzed in the model are due to the presence of missing data for which no imputation methods are expected for this endpoint. Please note that the Number Analyzed per Row includes those participants who contributed data at the specified time point.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reparixin | Change From Baseline to Fixed Endpoints in High-Sensitivity C Reactive Protein (Hs-CRP) | Day 3 | -30.7 mg/L | Standard Deviation 23.13 |
| Reparixin | Change From Baseline to Fixed Endpoints in High-Sensitivity C Reactive Protein (Hs-CRP) | EOT | 37.50 mg/L | Standard Deviation 151.54 |
| Reparixin | Change From Baseline to Fixed Endpoints in High-Sensitivity C Reactive Protein (Hs-CRP) | Day 7 ± 1 | -25.90 mg/L | Standard Deviation 95.74 |
| Reparixin | Change From Baseline to Fixed Endpoints in High-Sensitivity C Reactive Protein (Hs-CRP) | Day 28 ± 2 | -42.60 mg/L | Standard Deviation 30.15 |
| Reparixin | Change From Baseline to Fixed Endpoints in High-Sensitivity C Reactive Protein (Hs-CRP) | Day 21 ± 2 | -27.50 mg/L | Standard Deviation 72.23 |
| Reparixin | Change From Baseline to Fixed Endpoints in High-Sensitivity C Reactive Protein (Hs-CRP) | HD (hospital discharge) | -54.46 mg/L | Standard Deviation 63.12 |
| Reparixin | Change From Baseline to Fixed Endpoints in High-Sensitivity C Reactive Protein (Hs-CRP) | Day 14 ± 2 | -25.21 mg/L | Standard Deviation 66.53 |
| Placebo | Change From Baseline to Fixed Endpoints in High-Sensitivity C Reactive Protein (Hs-CRP) | HD (hospital discharge) | -84.83 mg/L | Standard Deviation 76.02 |
| Placebo | Change From Baseline to Fixed Endpoints in High-Sensitivity C Reactive Protein (Hs-CRP) | Day 3 | -21.67 mg/L | Standard Deviation 53.33 |
| Placebo | Change From Baseline to Fixed Endpoints in High-Sensitivity C Reactive Protein (Hs-CRP) | Day 7 ± 1 | -29.62 mg/L | Standard Deviation 37.85 |
| Placebo | Change From Baseline to Fixed Endpoints in High-Sensitivity C Reactive Protein (Hs-CRP) | Day 14 ± 2 | -45.24 mg/L | Standard Deviation 62.83 |
| Placebo | Change From Baseline to Fixed Endpoints in High-Sensitivity C Reactive Protein (Hs-CRP) | Day 21 ± 2 | -47.05 mg/L | Standard Deviation 99.48 |
| Placebo | Change From Baseline to Fixed Endpoints in High-Sensitivity C Reactive Protein (Hs-CRP) | EOT | -37.68 mg/L | Standard Deviation 76.26 |
| Placebo | Change From Baseline to Fixed Endpoints in High-Sensitivity C Reactive Protein (Hs-CRP) | Day 28 ± 2 | 9.65 mg/L | Standard Deviation 26.94 |
Comparison: to day 3 - Please note that the number of subjects in this analysis is not 270, but it is 15p-value: 0.68Mann-Whitney U test
Comparison: to day 7 - Please note that the number of subjects in this analysis is not 270, but it is 13p-value: 0.272Mann-Whitney U test
Comparison: to day 14 - Please note that the number of subjects in this analysis is not 270, but it is 13p-value: 1Mann-Whitney U test
Comparison: to day 21 - Please note that the number of subjects in this analysis is not 270, but it is 9p-value: 0.903Mann-Whitney U test
Comparison: to EOT - Please note that the number of subjects in this analysis is not 270, but it is 13p-value: 0.432Mann-Whitney U test
Comparison: to day 28 - Please note that the number of subjects in this analysis is not 270, but it is 6p-value: 0.105Mann-Whitney U test
Comparison: to HD - Please note that the number of subjects in this analysis is not 270, but it is 8p-value: 0.551Mann-Whitney U test
Secondary
Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio.
The PaO2/FiO2 ratio is used to determine the severity of lung injury in mechanically ventilated patients. A normal P/F Ratio is ≥ 400 and equivalent to a PaO2 ≥ 80 mmHg on room air. Low values of the PaO2/FIO2 ratio may be due to pathological conditions, primarily those of a respiratory nature (atelectasis, ARDS, acute pulmonary edema, pneumonia, etc.), as well as to alterations in hemodynamic status (cardiogenic shock, septic shock, etc.), or even both.
Time frame: At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months)
Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reparixin | Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio. | Day 7 ± 1 | 77.528 PaO2/FiO2 Ratio | Standard Deviation 106.383 |
| Reparixin | Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio. | Day 28 ± 2 | 145.043 PaO2/FiO2 Ratio | Standard Deviation 146.515 |
| Reparixin | Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio. | Day 21 ± 2 | 122.746 PaO2/FiO2 Ratio | Standard Deviation 114.603 |
| Reparixin | Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio. | HD (hospital discharge) | 228.999 PaO2/FiO2 Ratio | Standard Deviation 119.337 |
| Reparixin | Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio. | Day 14 ± 2 | 127.111 PaO2/FiO2 Ratio | Standard Deviation 135.063 |
| Reparixin | Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio. | Day 60 ± 2 | 200.000 PaO2/FiO2 Ratio | Standard Deviation 0 |
| Reparixin | Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio. | EoT | 140.575 PaO2/FiO2 Ratio | Standard Deviation 139.619 |
| Reparixin | Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio. | EOS | -5.333 PaO2/FiO2 Ratio | Standard Deviation 89.844 |
| Reparixin | Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio. | Day 3 | 30.329 PaO2/FiO2 Ratio | Standard Deviation 81.291 |
| Placebo | Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio. | EOS | -30.714 PaO2/FiO2 Ratio | Standard Deviation 191.669 |
| Placebo | Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio. | Day 3 | 0.398 PaO2/FiO2 Ratio | Standard Deviation 87.607 |
| Placebo | Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio. | Day 7 ± 1 | 65.291 PaO2/FiO2 Ratio | Standard Deviation 138.832 |
| Placebo | Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio. | Day 14 ± 2 | 111.220 PaO2/FiO2 Ratio | Standard Deviation 171.013 |
| Placebo | Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio. | Day 21 ± 2 | 62.520 PaO2/FiO2 Ratio | Standard Deviation 163.712 |
| Placebo | Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio. | EoT | 106.332 PaO2/FiO2 Ratio | Standard Deviation 144.608 |
| Placebo | Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio. | Day 28 ± 2 | -22.125 PaO2/FiO2 Ratio | Standard Deviation 123.435 |
| Placebo | Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio. | HD (hospital discharge) | 210.765 PaO2/FiO2 Ratio | Standard Deviation 112.418 |
| Placebo | Change From Baseline to Fixed Timepoints in PaO2/FiO2 Ratio. | Day 60 ± 2 | 334.000 PaO2/FiO2 Ratio | Standard Deviation 53.74 |
Comparison: at day 3 - Please note that the number of subjects in this analysis is not 270, but it is 245p-value: 0.005Mann-Whitney U test
Comparison: at day 7 - Please note that the number of subjects in this analysis is not 270, but it is 221p-value: 0.283Mann-Whitney U test
Comparison: at day 14 - Please note that the number of subjects in this analysis is not 270, but it is 117p-value: 0.512Mann-Whitney U test
Comparison: at day 21 - Please note that the number of subjects in this analysis is not 270, but it is 51p-value: 0.174Mann-Whitney U test
p-value: 0.133Mann-Whitney U test
Comparison: at day 28 ± 2 - Please note that the number of subjects in this analysis is not 270, but it is 29p-value: 0.009Mann-Whitney U test
Comparison: to HD - Please note that the number of subjects in this analysis is not 270, but it is 144p-value: 0.593Mann-Whitney U test
Comparison: to day 60 - Please note that the number of subjects in this analysis is not 270, but it is 3p-value: 0.54Mann-Whitney U test
Comparison: to EOS - Please note that the number of subjects in this analysis is not 270, but it is 13p-value: 0.224Mann-Whitney U test
Secondary
Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2).
Peripheral oxygen saturation (SpO2) monitoring by pulse oximetry is used to estimate the oxygen saturation of arterial blood (SaO2) and provides vital information about a patient's cardiorespiratory function.
Time frame: At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months)
Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reparixin | Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2). | Day 7 | 0.76 percentage of oxygenated hemoglobin | Standard Deviation 2.89 |
| Reparixin | Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2). | day 60 EoS | -2.70 percentage of oxygenated hemoglobin | Standard Deviation 0 |
| Reparixin | Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2). | Day 21 | -0.85 percentage of oxygenated hemoglobin | Standard Deviation 4.92 |
| Reparixin | Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2). | EoT | 0.24 percentage of oxygenated hemoglobin | Standard Deviation 2.69 |
| Reparixin | Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2). | Day 14 | 0.46 percentage of oxygenated hemoglobin | Standard Deviation 2.93 |
| Reparixin | Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2). | HD | 0.57 percentage of oxygenated hemoglobin | Standard Deviation 2.6 |
| Reparixin | Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2). | Day 28 | -0.99 percentage of oxygenated hemoglobin | Standard Deviation 6.15 |
| Reparixin | Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2). | EoS | -7.57 percentage of oxygenated hemoglobin | Standard Deviation 11.12 |
| Reparixin | Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2). | Day 3 | 0.79 percentage of oxygenated hemoglobin | Standard Deviation 2.88 |
| Placebo | Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2). | EoS | -11.01 percentage of oxygenated hemoglobin | Standard Deviation 18.49 |
| Placebo | Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2). | Day 3 | 0.36 percentage of oxygenated hemoglobin | Standard Deviation 2.78 |
| Placebo | Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2). | Day 7 | 0.49 percentage of oxygenated hemoglobin | Standard Deviation 3.38 |
| Placebo | Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2). | Day 14 | -0.83 percentage of oxygenated hemoglobin | Standard Deviation 3.99 |
| Placebo | Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2). | Day 21 | -5.35 percentage of oxygenated hemoglobin | Standard Deviation 11.82 |
| Placebo | Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2). | Day 28 | -1.56 percentage of oxygenated hemoglobin | Standard Deviation 6.78 |
| Placebo | Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2). | day 60 EoS | -2.00 percentage of oxygenated hemoglobin | Standard Deviation 0 |
| Placebo | Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2). | EoT | -0.68 percentage of oxygenated hemoglobin | Standard Deviation 3.76 |
| Placebo | Change From Baseline to Fixed Timepoints in Pulse Oximetry by Measurement of Peripheral Arterial Oxygen Saturation (SpO2). | HD | 0.28 percentage of oxygenated hemoglobin | Standard Deviation 2.76 |
Comparison: at day 3 - Please note that the number of subjects in this analysis is not 270, but it is 246.p-value: 0.053two-sample Mann-Whitney U test
Comparison: at day 7 - Please note that the number of subjects in this analysis is not 270, but it is 225.p-value: 0.245two-sample Mann-Whitney U test
Comparison: at day 14 - Please note that the number of subjects in this analysis is not 270, but it is 118.p-value: 0.067two-sample Mann-Whitney U test
Comparison: at day 21 - Please note that the number of subjects in this analysis is not 270, but it is 54.p-value: 0.051two-sample Mann-Whitney U test
Comparison: at day 28 - Please note that the number of subjects in this analysis is not 270, but it is 32.p-value: 0.684two-sample Mann-Whitney U test
Comparison: at EOS - Please note that the number of subjects in this analysis is not 246, but it is 14.p-value: 1two-sample Mann-Whitney U test
Comparison: at Day 60 - Please note that the number of subjects in this analysis is not 246, but it is 3.p-value: 0.48two-sample Mann-Whitney U test
Comparison: at Hospital discharge - Please note that the number of subjects in this analysis is 152.p-value: 0.638two-sample Mann-W hitney U test
Comparison: at EoT - Please note that the number of subjects in this analysis is 212.p-value: 0.137two-sample Mann-W hitney U test
Secondary
Change From Baseline to Fixed Timepoints of Partial Pressure of Oxygen (PaO2)
PaO2-the oxygen pressure in arterial blood. The PaO2 reflects how well oxygen is able to move from the lungs to the blood. It is often altered by severe illnesses, with the PaO2 test results used to guide treatment.
Time frame: At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months)
Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reparixin | Change From Baseline to Fixed Timepoints of Partial Pressure of Oxygen (PaO2) | Day 60 | 1 mmHg | Standard Deviation 73 |
| Reparixin | Change From Baseline to Fixed Timepoints of Partial Pressure of Oxygen (PaO2) | Day 7 | 3.147 mmHg | Standard Deviation 33.541 |
| Reparixin | Change From Baseline to Fixed Timepoints of Partial Pressure of Oxygen (PaO2) | Day 14 | 4.002 mmHg | Standard Deviation 54.235 |
| Reparixin | Change From Baseline to Fixed Timepoints of Partial Pressure of Oxygen (PaO2) | Day 21 | 3.388 mmHg | Standard Deviation 43.52 |
| Reparixin | Change From Baseline to Fixed Timepoints of Partial Pressure of Oxygen (PaO2) | Day 28 | -6.700 mmHg | Standard Deviation 31.896 |
| Reparixin | Change From Baseline to Fixed Timepoints of Partial Pressure of Oxygen (PaO2) | HD | -3.633 mmHg | Standard Deviation 29.723 |
| Reparixin | Change From Baseline to Fixed Timepoints of Partial Pressure of Oxygen (PaO2) | EOT | 3.020 mmHg | Standard Deviation 50.296 |
| Reparixin | Change From Baseline to Fixed Timepoints of Partial Pressure of Oxygen (PaO2) | EOS | 1.825 mmHg | Standard Deviation 20.57 |
| Reparixin | Change From Baseline to Fixed Timepoints of Partial Pressure of Oxygen (PaO2) | Day 3 | 13.377 mmHg | Standard Deviation 36.568 |
| Placebo | Change From Baseline to Fixed Timepoints of Partial Pressure of Oxygen (PaO2) | Day 3 | -5.274 mmHg | Standard Deviation 41.103 |
| Placebo | Change From Baseline to Fixed Timepoints of Partial Pressure of Oxygen (PaO2) | Day 28 | -52.171 mmHg | Standard Deviation 76.278 |
| Placebo | Change From Baseline to Fixed Timepoints of Partial Pressure of Oxygen (PaO2) | Day 7 | 12.777 mmHg | Standard Deviation 81.367 |
| Placebo | Change From Baseline to Fixed Timepoints of Partial Pressure of Oxygen (PaO2) | EOT | -7.189 mmHg | Standard Deviation 55.55 |
| Placebo | Change From Baseline to Fixed Timepoints of Partial Pressure of Oxygen (PaO2) | Day 14 | -7.257 mmHg | Standard Deviation 50.645 |
| Placebo | Change From Baseline to Fixed Timepoints of Partial Pressure of Oxygen (PaO2) | HD | -8.869 mmHg | Standard Deviation 37.953 |
| Placebo | Change From Baseline to Fixed Timepoints of Partial Pressure of Oxygen (PaO2) | Day 21 | -14.014 mmHg | Standard Deviation 54.603 |
| Placebo | Change From Baseline to Fixed Timepoints of Partial Pressure of Oxygen (PaO2) | EOS | 51.950 mmHg | Standard Deviation 215.446 |
Comparison: at day 3 - Please note that the number of subjects in this analysis is 168p-value: 0.002two-sample Mann-Whitney U test
Comparison: at day 7 - Please note that the number of subjects in this analysis is not 168, but it is 146p-value: 0.943two-sample Mann-Whitney U test
Comparison: at day 14 - Please note that the number of subjects in this analysis is not 168, but it is 76p-value: 0.88two-sample Mann-Whitney U test
Comparison: at day 21 - Please note that the number of subjects in this analysis is not 168, but it is 38p-value: 0.458Wilcoxon (Mann-Whitney)
Comparison: at day 28 - Please note that the number of subjects in this analysis is not 168, but it is 23.p-value: 0.285two-sample Mann-Whitney U test
Comparison: at EOS - Please note that the number of subjects in this analysis is not 168, but it is 8p-value: 0.885two-sample Mann-Whitney U test
Comparison: at HD - Please note that the number of subjects in this analysis is not 270, but it is 74p-value: =0.583two-sample Mann-Whitney U test
Comparison: at End of treatment - Please note that the number of subjects in this analysis is not 270, but it is 131.p-value: 0.5two-sample Mann-Whitney U test
Secondary
Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points
Clinical status is analyzed based on the 7-point WHO-OS. The 7-point WHO Ordinal Scale of clinical improvement (WHO-OS), comprises the following categories: 1: not hospitalized, with resumption of normal activities; 2: not hospitalized, but unable to resume normal activities; 3: hospitalized, not requiring supplemental oxygen; 4: hospitalized, requiring supplemental oxygen; 5: hospitalized, requiring high-flow oxygen therapy, non-invasive mechanical ventilation, or both; 6: hospitalized, requiring ECMO, invasive mechanical ventilation, or both; 7: death. The higher the score, the worse the outcome.
Time frame: At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months)
Population: FAS Full Analysis Set: set which consisted of all randomized subjects who received at least one dose of the IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 28 score 1 | 100 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 14 score 5 | 17 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 28 score 2 | 8 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 3 score 6 | 0 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 28 score 3 | 7 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 14 score 6 | 4 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 28 score 4 | 8 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 7 score 4 | 66 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 28 score 5 | 2 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 14 score 7 | 2 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 28 score 6 | 4 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 3 score 4 | 85 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 28 score 7 | 2 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 21 score 1 | 74 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoT score 1 | 3 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 7 score 5 | 54 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoT score 2 | 0 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 21 score 2 | 8 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoT score 3 | 92 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 3 score 7 | 0 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoT score 4 | 36 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 21 score 3 | 13 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoT score 5 | 25 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 7 score 6 | 6 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoT score 6 | 7 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 21 score 4 | 14 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoT score 7 | 1 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 3 score 3 | 5 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 60 score 1 | 125 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 21 score 5 | 6 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 60 score 2 | 9 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 7 score 7 | 1 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 60 score 3 | 1 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 21 score 6 | 5 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 60 score 4 | 0 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 7 score 1 | 7 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 60 score 5 | 1 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 21 score 7 | 1 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 60 score 6 | 0 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 14 score 1 | 52 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 60 score 7 | 0 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | HD score 1 | 11 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 90 score 1 | 14 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 3 score 5 | 81 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | HD score 2 | 2 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 90 score 2 | 0 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 14 score 2 | 10 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 90 score 3 | 0 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | HD score 3 | 109 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 90 score 4 | 0 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 7 score 2 | 1 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 90 score 5 | 0 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | HD score 4 | 10 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 90 score 6 | 0 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 14 score 3 | 28 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 90 score 7 | 0 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | HD score 5 | 0 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoS score 1 | 132 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 3 score 2 | 0 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoS score 2 | 7 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoS score 3 | 1 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | HD score 6 | 0 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoS score 4 | 2 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 14 score 4 | 29 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoS score 5 | 3 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | HD score 7 | 0 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoS score 6 | 1 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 7 score 3 | 31 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoS score 7 | 8 number of patients with event |
| Reparixin | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 3 score 1 | 0 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoS score 7 | 5 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 3 score 1 | 0 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 3 score 2 | 0 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 3 score 3 | 1 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 3 score 4 | 40 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 3 score 5 | 42 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 3 score 6 | 0 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 3 score 7 | 1 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 7 score 1 | 2 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 7 score 2 | 0 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 7 score 3 | 16 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 7 score 4 | 27 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 7 score 5 | 30 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 7 score 6 | 5 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 7 score 7 | 0 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 14 score 1 | 24 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 14 score 2 | 3 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 14 score 3 | 12 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 14 score 4 | 13 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 14 score 5 | 10 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 14 score 6 | 4 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 14 score 7 | 1 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 21 score 1 | 36 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 21 score 2 | 2 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 21 score 3 | 5 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 21 score 4 | 5 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 21 score 5 | 5 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 21 score 6 | 0 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 21 score 7 | 2 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | HD score 1 | 6 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | HD score 2 | 4 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | HD score 3 | 48 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | HD score 4 | 3 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | HD score 5 | 0 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | HD score 6 | 0 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | HD score 7 | 0 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 28 score 1 | 40 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 28 score 2 | 8 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 28 score 3 | 1 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 28 score 4 | 5 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 28 score 5 | 2 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 28 score 6 | 2 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | day 28 score 7 | 1 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoT score 1 | 2 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoT score 2 | 0 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoT score 3 | 36 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoT score 4 | 18 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoT score 5 | 15 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoT score 6 | 5 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoT score 7 | 1 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 60 score 1 | 56 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 60 score 2 | 6 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 60 score 3 | 0 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 60 score 4 | 1 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 60 score 5 | 2 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 60 score 6 | 0 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 60 score 7 | 0 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 90 score 1 | 4 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoS score 2 | 6 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 90 score 2 | 0 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 90 score 3 | 0 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 90 score 4 | 0 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 90 score 5 | 0 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 90 score 6 | 0 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | Day 90 score 7 | 0 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoS score 1 | 57 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoS score 3 | 0 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoS score 4 | 1 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoS score 5 | 4 number of patients with event |
| Placebo | Clinical Status Either in Hospital or at Home (7-point WHO-OS) at Fixed Time Points | EoS score 6 | 2 number of patients with event |
Comparison: day 3 - please note that the number of subjects in this analysis is not 270 but 255p-value: 0.444Wilcoxon (Mann-Whitney)
Comparison: day 7 - please note that the number of subjects in this analysis is not 270 but 246p-value: 0.357Wilcoxon (Mann-Whitney)
Comparison: day 14 - please note that the number of subjects in this analysis is not 270 but 209p-value: 0.484Wilcoxon (Mann-Whitney)
Comparison: day 21 - please note that the number of subjects in this analysis is not 270 but 176p-value: 0.753Wilcoxon (Mann-Whitney)
Comparison: day 28 - please note that the number of subjects in this analysis is not 270 but 190p-value: 0.26Wilcoxon (Mann-Whitney)
Comparison: day 60 - please note that the number of subjects in this analysis is not 270 but 201p-value: 0.19Wilcoxon (Mann-Whitney)
Comparison: day 90 - please note that the number of subjects in this analysis is not 270 but 18p-value: 1Wilcoxon (Mann-Whitney)
Comparison: EOS - please note that the number of subjects in this analysis is not 270 but 229p-value: 0.074Wilcoxon (Mann-Whitney)
Comparison: EOT - please note that the number of subjects in this analysis is not 270 but 241p-value: 0.193two-sample Mann-Whitney U test
Comparison: Hospital discharge - please note that the number of subjects in this analysis is not 270 but 195p-value: 0.131two-sample Mann-Whitney U test
Secondary
Duration of ICU Admission up to Day 60
Admission to intensive care unit or ICU is linked to worsening of respiratory parameters compared to baseline.
Time frame: Up to day 60
Population: FAS population is used in this table. Discrepancies between the total number of patients in the FAS and patients actually analyzed in the model are due to the presence of missing data for which no imputation methods are expected for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reparixin | Duration of ICU Admission up to Day 60 | 17.9 Days | Standard Deviation 10.1 |
| Placebo | Duration of ICU Admission up to Day 60 | 11.4 Days | Standard Deviation 6.7 |
p-value: 0.137two-sample Mann-Whitney U test
Secondary
Duration of Invasive Mechanical Ventilation, or ECMO up to Day 60
Invasive mechanical ventilation is defined as the delivery of positive pressure to the lungs via an endotracheal or tracheostomy tube. During mechanical ventilation, a predetermined mixture of air (ie, oxygen and other gases) is forced into the central airways and then flows into the alveoli.
Time frame: Up to day 60
Population: FAS population is used in this table. Discrepancies between the total number of patients in the FAS and patients actually analyzed in the model are due to the presence of missing data for which no imputation methods are expected for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reparixin | Duration of Invasive Mechanical Ventilation, or ECMO up to Day 60 | 24.8 Days | Standard Deviation 16.8 |
| Placebo | Duration of Invasive Mechanical Ventilation, or ECMO up to Day 60 | 15.9 Days | Standard Deviation 13.9 |
Comparison: Number of subjects included in analysis: 17p-value: 0.267two-sample Mann-Whitney U test
Secondary
Duration of Non-invasive Mechanical Ventilation up to Day 60
Non-invasive ventilation (NIV) is the delivery of oxygen (ventilation support) via a face mask and therefore eliminating the need of an endotracheal airway. NIV achieves comparative physiological benefits to conventional mechanical ventilation by reducing the work of breathing and improving gas exchange.
Time frame: From baseline up to day 60
Population: FAS population is used in this table. Discrepancies between the total number of patients in the FAS and patients actually analyzed in the model are due to the presence of missing data for which no imputation methods are expected for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reparixin | Duration of Non-invasive Mechanical Ventilation up to Day 60 | 9.0 days | Standard Deviation 7.9 |
| Placebo | Duration of Non-invasive Mechanical Ventilation up to Day 60 | 10.1 days | Standard Deviation 7.5 |
p-value: 0.485two-sample Mann-Whitney U test
Secondary
Duration of Supplemental Oxygen Treatment up to Day 28
This endpoint is expressed as: * The number and proportion along with the 95% CI (Clopper-Pearson's formula) of patients using supplemental oxygen treatment by treatment group; * The Cumulative duration of supplemental oxygen treatment in days analyzed by means of descriptive statistics by treatment. This latter is reported in the system.
Time frame: From baseline up to day 28
Population: FAS population is used in this table. Discrepancies between the total number of patients in the FAS and patients actually analyzed in the model are due to the presence of missing data for which no imputation methods are expected for this endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Reparixin | Duration of Supplemental Oxygen Treatment up to Day 28 | 10.5 day | Standard Deviation 7.3 |
| Placebo | Duration of Supplemental Oxygen Treatment up to Day 28 | 10.8 day | Standard Deviation 6.8 |
Comparison: Please note that the number of patients in this analysis is not 270 but 255, because patients who used supplement oxygen were 174 in the Reparixin group and 81 in the placebo group.p-value: 0.447two-sample Mann-Whitney U test
Secondary
Freedom From (Time to) Death or Respiratory Failure up to Day 90
Freedom from (time to) death or respiratory failure (need of invasive mechanical ventilation or ECMO or admission to ICU linked to worsening of respiratory parameters compared to baseline) at baseline, day 3, day 7, day 14, day 21, day 28, day 60, day 90 was performed using the same Kaplan-Meier analysis and the one-sided log-rank test that were used to test for differences between groups.
Time frame: at baseline, day 3, day 7, day 14, day 21, day 28, day 60, day 90
Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reparixin | Freedom From (Time to) Death or Respiratory Failure up to Day 90 | day 1 | 0 participants with event |
| Reparixin | Freedom From (Time to) Death or Respiratory Failure up to Day 90 | day 3 | 2 participants with event |
| Reparixin | Freedom From (Time to) Death or Respiratory Failure up to Day 90 | day 7 | 4 participants with event |
| Reparixin | Freedom From (Time to) Death or Respiratory Failure up to Day 90 | day 14 | 9 participants with event |
| Reparixin | Freedom From (Time to) Death or Respiratory Failure up to Day 90 | day 21 | 11 participants with event |
| Reparixin | Freedom From (Time to) Death or Respiratory Failure up to Day 90 | day 28 | 16 participants with event |
| Reparixin | Freedom From (Time to) Death or Respiratory Failure up to Day 90 | day 60 | 103 participants with event |
| Reparixin | Freedom From (Time to) Death or Respiratory Failure up to Day 90 | day 90 | 154 participants with event |
| Placebo | Freedom From (Time to) Death or Respiratory Failure up to Day 90 | day 90 | 72 participants with event |
| Placebo | Freedom From (Time to) Death or Respiratory Failure up to Day 90 | day 1 | 0 participants with event |
| Placebo | Freedom From (Time to) Death or Respiratory Failure up to Day 90 | day 21 | 5 participants with event |
| Placebo | Freedom From (Time to) Death or Respiratory Failure up to Day 90 | day 3 | 1 participants with event |
| Placebo | Freedom From (Time to) Death or Respiratory Failure up to Day 90 | day 60 | 49 participants with event |
| Placebo | Freedom From (Time to) Death or Respiratory Failure up to Day 90 | day 7 | 2 participants with event |
| Placebo | Freedom From (Time to) Death or Respiratory Failure up to Day 90 | day 28 | 6 participants with event |
| Placebo | Freedom From (Time to) Death or Respiratory Failure up to Day 90 | day 14 | 5 participants with event |
p-value: 0.33607Log Rank
Secondary
Incidence of ICU Admission Until Day 28
This is a key secondary efficacy endpoint. Admissions to Intensive Care Unit (ICU) had to be considered only in presence of significant worsening of respiratory status. This condition was objectively identified by means of a decrease of PaO2/FiO2 ratio of at least 40% from the baseline value or by a worsening of Investigator's Interpretation.
Time frame: Until day 28
Population: FAS population is used in this table. Discrepancies between the total number of patients in the FAS and patients actually analyzed in the logistic regression model are due to the presence of missing data for which no imputation methods are expected for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reparixin | Incidence of ICU Admission Until Day 28 | 27 participants |
| Placebo | Incidence of ICU Admission Until Day 28 | 18 participants |
p-value: 0.16895% CI: [0.247, 1.277]Regression, Logistic
Secondary
Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints
Changes from baseline in clinical severity score are analyzed based on the 7-point WHO-OS. The 7-point WHO Ordinal Scale of clinical improvement (WHO-OS), comprises the following categories: 1: not hospitalized, with resumption of normal activities; 2: not hospitalized, but unable to resume normal activities; 3: hospitalized, not requiring supplemental oxygen; 4: hospitalized, requiring supplemental oxygen; 5: hospitalized, requiring high-flow oxygen therapy, non-invasive mechanical ventilation, or both; 6: hospitalized, requiring ECMO, invasive mechanical ventilation, or both; 7: death.
Time frame: At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months)
Population: The Full Analysis Set (FAS) consisted of all randomized subjects who received at least one dose of the IMP.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Reparixin | Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints | Day 3 | -0.1 score on a scale | Standard Deviation 0.4 |
| Reparixin | Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints | Day 7 | -0.4 score on a scale | Standard Deviation 1 |
| Reparixin | Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints | Day 14 | -1.7 score on a scale | Standard Deviation 1.5 |
| Reparixin | Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints | Day 21 | -2.4 score on a scale | Standard Deviation 1.5 |
| Reparixin | Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints | EoT | -0.9 score on a scale | Standard Deviation 1 |
| Reparixin | Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints | Day 28 | -2.8 score on a scale | Standard Deviation 1.4 |
| Reparixin | Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints | Hospital Discharge | -1.6 score on a scale | Standard Deviation 0.9 |
| Reparixin | Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints | Day 60 | -3.4 score on a scale | Standard Deviation 0.6 |
| Reparixin | Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints | Day 90 | -3.4 score on a scale | Standard Deviation 0.6 |
| Reparixin | Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints | EOS | -3.0 score on a scale | Standard Deviation 1.5 |
| Placebo | Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints | Day 60 | -3.2 score on a scale | Standard Deviation 0.9 |
| Placebo | Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints | Day 3 | 0.0 score on a scale | Standard Deviation 0.5 |
| Placebo | Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints | Day 28 | -2.6 score on a scale | Standard Deviation 1.5 |
| Placebo | Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints | Day 7 | -0.3 score on a scale | Standard Deviation 0.9 |
| Placebo | Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints | EOS | -2.6 score on a scale | Standard Deviation 1.8 |
| Placebo | Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints | Day 14 | -1.5 score on a scale | Standard Deviation 1.6 |
| Placebo | Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints | Hospital Discharge | -1.6 score on a scale | Standard Deviation 0.8 |
| Placebo | Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints | Day 21 | -2.3 score on a scale | Standard Deviation 1.6 |
| Placebo | Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints | Day 90 | -3.5 score on a scale | Standard Deviation 0.6 |
| Placebo | Mean Changes From Baseline in Clinical Severity Score Based on the 7-point WHO-OS at Fixed Timepoints | EoT | -0.7 score on a scale | Standard Deviation 1.1 |
Comparison: At Day 3 - Please note that the number of subjects in this analysis is not 270 but 255p-value: 0.047Wilcoxon (Mann-Whitney)
p-value: 0.262Wilcoxon (Mann-Whitney)
Comparison: At Day 14 - Please note that the number of subjects in this analysis is not 270 but 209p-value: 0.367Wilcoxon (Mann-Whitney)
Comparison: At Day 21 - Please note that the number of subjects in this analysis is not 270 but 176p-value: 0.882Wilcoxon (Mann-Whitney)
Comparison: At Day 28 - Please note that the number of subjects in this analysis is not 270 but 190p-value: 0.19Wilcoxon (Mann-Whitney)
Comparison: At Day 60 - Please note that the number of subjects in this analysis is not 270 but 201p-value: 0.161Mann-Whitney U test
Comparison: At Day 90 - Please note that the number of subjects in this analysis is not 270 but 18p-value: 0.853Mann-Whitney U test
Comparison: At EOS - Please note that the number of subjects in this analysis is not 270 but 229p-value: 0.068Wilcoxon (Mann-Whitney)
Comparison: At hospital discharge (HD) - Please note that the number of subjects in this analysis is not 270 but 195p-value: 0.672Wilcoxon (Mann-Whitney)
Comparison: At end of treatment (EoT) - Please note that the number of subjects in this analysis is not 270 but 241p-value: 0.153Wilcoxon (Mann-Whitney)
Secondary
Mortality Rates up to Day 28
This key secondary efficacy endpoint describes number and proportion along with the 95% CI (Clopper-Pearson's formula) of patients who died up to Day 28.
Time frame: Up to Day 28
Population: FAS population is used in this table. Discrepancies between the total number of patients in the FAS and patients actually analyzed in the logistic regression model are due to the presence of missing data for which no imputation methods are expected for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reparixin | Mortality Rates up to Day 28 | 10 participants |
| Placebo | Mortality Rates up to Day 28 | 7 participants |
p-value: 0.1795% CI: [0.158, 1.386]Two-sided regression, Logistic
Secondary
Mortality Rates up to Days 60 and 90
Mortality rate, or death rate, is a measure of the number of deaths (in general, or due to a specific cause) in a particular population, scaled to the size of that population, per unit of time. The death event variable is defined as the proportion of patients died up to Day 90.
Time frame: up to Days 60 and 90
Population: FAS population is used in this table. Discrepancies between the total number of patients in the FAS and patients actually analyzed in the model are due to the presence of missing data for which no imputation methods are expected for this endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reparixin | Mortality Rates up to Days 60 and 90 | Day 60 | 11 dead patients |
| Reparixin | Mortality Rates up to Days 60 and 90 | Day 90 | 11 dead patients |
| Placebo | Mortality Rates up to Days 60 and 90 | Day 60 | 7 dead patients |
| Placebo | Mortality Rates up to Days 60 and 90 | Day 90 | 7 dead patients |
Comparison: up to day 60p-value: 0.23295% CI: [0.178, 1.522]Regression, Logistic
Comparison: Up to Day 90p-value: 0.15895% CI: [0.034, 1.782]Regression, Logistic
Secondary
Number of Patients Requiring Invasive Mechanical Ventilation Use, or ECMO up to Day 28 and up to Day 60
Invasive mechanical ventilation is defined as the delivery of positive pressure to the lungs via an endotracheal or tracheostomy tube. During mechanical ventilation, a predetermined mixture of air (ie, oxygen and other gases) is forced into the central airways and then flows into the alveoli.
Time frame: day 28 and Day 60
Population: FAS population is used in this table. Discrepancies between the total number of patients in the FAS and patients actually analyzed in the model at Day 28 are due to the presence of missing data for which no imputation methods are expected for this endpoint.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reparixin | Number of Patients Requiring Invasive Mechanical Ventilation Use, or ECMO up to Day 28 and up to Day 60 | Up to day 28 | 9 Number of patient with event |
| Reparixin | Number of Patients Requiring Invasive Mechanical Ventilation Use, or ECMO up to Day 28 and up to Day 60 | Up to day 60 | 9 Number of patient with event |
| Placebo | Number of Patients Requiring Invasive Mechanical Ventilation Use, or ECMO up to Day 28 and up to Day 60 | Up to day 28 | 10 Number of patient with event |
| Placebo | Number of Patients Requiring Invasive Mechanical Ventilation Use, or ECMO up to Day 28 and up to Day 60 | Up to day 60 | 10 Number of patient with event |
Comparison: At day 28 - Please note that the number of patients in this analysis is not 270 but 245, because patients requiring IMV or ECMO were 163 in the Reparixin group and 82 in the placebo group.p-value: 0.065Chi-squared
p-value: 0.072Chi-squared
Secondary
Number of Patients With Clinical Improvement 1 up to Day 28 (Decline of 1 Category in the 7-point WHO-OS)
Clinical improvement 1 is defined as the decline of 1 category in the 7-point WHO-OS up to Date 28. The clinical improvement 1 up to Day 28 was analyzed as described for time to recovery: an event was considered as such, if patient declined of at least 1 category in the 7-point WHO-OS respect to the baseline, otherwise it was be considered free of event.
Time frame: Day 1 (baseline), Days 3, 7, 14, 21, 28.
Population: The Full Analysis Set (FAS) consisted of all randomized subjects who received at least one dose of the IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reparixin | Number of Patients With Clinical Improvement 1 up to Day 28 (Decline of 1 Category in the 7-point WHO-OS) | Day 1 | 0 number of patients with event |
| Reparixin | Number of Patients With Clinical Improvement 1 up to Day 28 (Decline of 1 Category in the 7-point WHO-OS) | Day 3 | 19 number of patients with event |
| Reparixin | Number of Patients With Clinical Improvement 1 up to Day 28 (Decline of 1 Category in the 7-point WHO-OS) | Day 7 | 56 number of patients with event |
| Reparixin | Number of Patients With Clinical Improvement 1 up to Day 28 (Decline of 1 Category in the 7-point WHO-OS) | Day 14 | 123 number of patients with event |
| Reparixin | Number of Patients With Clinical Improvement 1 up to Day 28 (Decline of 1 Category in the 7-point WHO-OS) | Day 21 | 146 number of patients with event |
| Reparixin | Number of Patients With Clinical Improvement 1 up to Day 28 (Decline of 1 Category in the 7-point WHO-OS) | Day 28 | 152 number of patients with event |
| Placebo | Number of Patients With Clinical Improvement 1 up to Day 28 (Decline of 1 Category in the 7-point WHO-OS) | Day 21 | 66 number of patients with event |
| Placebo | Number of Patients With Clinical Improvement 1 up to Day 28 (Decline of 1 Category in the 7-point WHO-OS) | Day 1 | 0 number of patients with event |
| Placebo | Number of Patients With Clinical Improvement 1 up to Day 28 (Decline of 1 Category in the 7-point WHO-OS) | Day 14 | 50 number of patients with event |
| Placebo | Number of Patients With Clinical Improvement 1 up to Day 28 (Decline of 1 Category in the 7-point WHO-OS) | Day 3 | 6 number of patients with event |
| Placebo | Number of Patients With Clinical Improvement 1 up to Day 28 (Decline of 1 Category in the 7-point WHO-OS) | Day 28 | 68 number of patients with event |
| Placebo | Number of Patients With Clinical Improvement 1 up to Day 28 (Decline of 1 Category in the 7-point WHO-OS) | Day 7 | 22 number of patients with event |
p-value: 0.07Grey's test
Secondary
Number of Patients With Clinical Improvement 2 up to Day 28 (Decline of 2 Categories in the 7-point WHO-OS)
Clinical improvement 2 is defined as the decline of 2 categories in the 7-point WHO-OS) up to Date 28. Clinical improvement 2 up to Date 28 was analyzed as described for time to recovery. An event was considered as such, if patient declined of at least 2 categories in the 7-point WHO-OS respect to the baseline, otherwise it was considered free of event.
Time frame: Day 1 (baseline), Days 3, 7, 14, 21, 28
Population: The Full Analysis Set (FAS) consisted of all randomized subjects who received at least one dose of the IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reparixin | Number of Patients With Clinical Improvement 2 up to Day 28 (Decline of 2 Categories in the 7-point WHO-OS) | Day 14 | 78 number of patients with event |
| Reparixin | Number of Patients With Clinical Improvement 2 up to Day 28 (Decline of 2 Categories in the 7-point WHO-OS) | Day 3 | 0 number of patients with event |
| Reparixin | Number of Patients With Clinical Improvement 2 up to Day 28 (Decline of 2 Categories in the 7-point WHO-OS) | Day 21 | 105 number of patients with event |
| Reparixin | Number of Patients With Clinical Improvement 2 up to Day 28 (Decline of 2 Categories in the 7-point WHO-OS) | Day 1 | 0 number of patients with event |
| Reparixin | Number of Patients With Clinical Improvement 2 up to Day 28 (Decline of 2 Categories in the 7-point WHO-OS) | Day 28 | 120 number of patients with event |
| Reparixin | Number of Patients With Clinical Improvement 2 up to Day 28 (Decline of 2 Categories in the 7-point WHO-OS) | Day 7 | 19 number of patients with event |
| Placebo | Number of Patients With Clinical Improvement 2 up to Day 28 (Decline of 2 Categories in the 7-point WHO-OS) | Day 28 | 56 number of patients with event |
| Placebo | Number of Patients With Clinical Improvement 2 up to Day 28 (Decline of 2 Categories in the 7-point WHO-OS) | Day 1 | 0 number of patients with event |
| Placebo | Number of Patients With Clinical Improvement 2 up to Day 28 (Decline of 2 Categories in the 7-point WHO-OS) | Day 3 | 0 number of patients with event |
| Placebo | Number of Patients With Clinical Improvement 2 up to Day 28 (Decline of 2 Categories in the 7-point WHO-OS) | Day 14 | 35 number of patients with event |
| Placebo | Number of Patients With Clinical Improvement 2 up to Day 28 (Decline of 2 Categories in the 7-point WHO-OS) | Day 21 | 50 number of patients with event |
| Placebo | Number of Patients With Clinical Improvement 2 up to Day 28 (Decline of 2 Categories in the 7-point WHO-OS) | Day 7 | 6 number of patients with event |
Comparison: Comparison at day 28p-value: 0.668Gray's test
Secondary
Number of Subjects Who Exhibited at Least 1 TEAE, at Least 1 Severe TEAE, at Least 1 Serious TEAE, at Least 1 Non-serious TEAE, at Least 1 ADR, at Least 1 Serious ADR, at Least 1 TEAE Leading to Discontinuation of IMP, Etc.
AE= An adverse event is any untoward or unfavorable medical occurrence in a human. subject, including any abnormal sign (for example, abnormal physical exam or. laboratory finding), symptom, or disease, temporally associated with the subject's. serious AE=a SAE iA serious adverse event (SAE) in human drug trials is defined as any untoward medical occurrence that at any dose results in death Is life-threatening Requires inpatient hospitalization or causes prolongation of existing hospitalization Results in persistent or significant disability/incapacity May have caused a congenital anomaly/birth defect Requires intervention to prevent permanent impairment or damage. The term life-threatening in the definition of serious refers to an event in which the patient was at risk of death at the time of the event; it does not refer to an event which hypothetically might have caused death if it were more severe. Do note that starting from this point the safety endpoint is analysed.
Time frame: Throughout the study, till Day 90 (= end of the follow-up period).
Population: The Safety set (SAF) consisted of all randomized subjects who received at least one dose of the IMP. The SAF population was analyzed according to the actual treatment received and was used to present results on safety data.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reparixin | Number of Subjects Who Exhibited at Least 1 TEAE, at Least 1 Severe TEAE, at Least 1 Serious TEAE, at Least 1 Non-serious TEAE, at Least 1 ADR, at Least 1 Serious ADR, at Least 1 TEAE Leading to Discontinuation of IMP, Etc. | Number of Subjects with at least one TEAE | 83 number of subjects |
| Reparixin | Number of Subjects Who Exhibited at Least 1 TEAE, at Least 1 Severe TEAE, at Least 1 Serious TEAE, at Least 1 Non-serious TEAE, at Least 1 ADR, at Least 1 Serious ADR, at Least 1 TEAE Leading to Discontinuation of IMP, Etc. | Number of Subjects with at least one serious TEAE | 20 number of subjects |
| Reparixin | Number of Subjects Who Exhibited at Least 1 TEAE, at Least 1 Severe TEAE, at Least 1 Serious TEAE, at Least 1 Non-serious TEAE, at Least 1 ADR, at Least 1 Serious ADR, at Least 1 TEAE Leading to Discontinuation of IMP, Etc. | Number of Subjects with at least one severe TEAE | 16 number of subjects |
| Reparixin | Number of Subjects Who Exhibited at Least 1 TEAE, at Least 1 Severe TEAE, at Least 1 Serious TEAE, at Least 1 Non-serious TEAE, at Least 1 ADR, at Least 1 Serious ADR, at Least 1 TEAE Leading to Discontinuation of IMP, Etc. | N. sub with at least 1TEAE leading to quit IMP | 19 number of subjects |
| Reparixin | Number of Subjects Who Exhibited at Least 1 TEAE, at Least 1 Severe TEAE, at Least 1 Serious TEAE, at Least 1 Non-serious TEAE, at Least 1 ADR, at Least 1 Serious ADR, at Least 1 TEAE Leading to Discontinuation of IMP, Etc. | Number of subjects with at least 1TEAE leading to quit the study | 1 number of subjects |
| Reparixin | Number of Subjects Who Exhibited at Least 1 TEAE, at Least 1 Severe TEAE, at Least 1 Serious TEAE, at Least 1 Non-serious TEAE, at Least 1 ADR, at Least 1 Serious ADR, at Least 1 TEAE Leading to Discontinuation of IMP, Etc. | Number of Subjects with TEAEs leading to death | 10 number of subjects |
| Placebo | Number of Subjects Who Exhibited at Least 1 TEAE, at Least 1 Severe TEAE, at Least 1 Serious TEAE, at Least 1 Non-serious TEAE, at Least 1 ADR, at Least 1 Serious ADR, at Least 1 TEAE Leading to Discontinuation of IMP, Etc. | Number of subjects with at least 1TEAE leading to quit the study | 0 number of subjects |
| Placebo | Number of Subjects Who Exhibited at Least 1 TEAE, at Least 1 Severe TEAE, at Least 1 Serious TEAE, at Least 1 Non-serious TEAE, at Least 1 ADR, at Least 1 Serious ADR, at Least 1 TEAE Leading to Discontinuation of IMP, Etc. | Number of Subjects with at least one TEAE | 48 number of subjects |
| Placebo | Number of Subjects Who Exhibited at Least 1 TEAE, at Least 1 Severe TEAE, at Least 1 Serious TEAE, at Least 1 Non-serious TEAE, at Least 1 ADR, at Least 1 Serious ADR, at Least 1 TEAE Leading to Discontinuation of IMP, Etc. | N. sub with at least 1TEAE leading to quit IMP | 11 number of subjects |
| Placebo | Number of Subjects Who Exhibited at Least 1 TEAE, at Least 1 Severe TEAE, at Least 1 Serious TEAE, at Least 1 Non-serious TEAE, at Least 1 ADR, at Least 1 Serious ADR, at Least 1 TEAE Leading to Discontinuation of IMP, Etc. | Number of Subjects with at least one serious TEAE | 13 number of subjects |
| Placebo | Number of Subjects Who Exhibited at Least 1 TEAE, at Least 1 Severe TEAE, at Least 1 Serious TEAE, at Least 1 Non-serious TEAE, at Least 1 ADR, at Least 1 Serious ADR, at Least 1 TEAE Leading to Discontinuation of IMP, Etc. | Number of Subjects with TEAEs leading to death | 7 number of subjects |
| Placebo | Number of Subjects Who Exhibited at Least 1 TEAE, at Least 1 Severe TEAE, at Least 1 Serious TEAE, at Least 1 Non-serious TEAE, at Least 1 ADR, at Least 1 Serious ADR, at Least 1 TEAE Leading to Discontinuation of IMP, Etc. | Number of Subjects with at least one severe TEAE | 12 number of subjects |
Secondary
Percentage of Participants With Clinical Improvement 1 up to Day 28
Clinical improvement 1 up to Date 28 for this outcome is expressed as cumulative incidence function (CIF in %). CIF allows for estimation of the occurrence of an event while taking into account the following competing risks: death, reasons for discontinuation for Adverse events and patient transferred to another institution. Estimates are calculated using a nonparametric method. The null hypothesis is that the cumulative incidence functions are identical across treatment groups.
Time frame: At day 28
Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reparixin | Percentage of Participants With Clinical Improvement 1 up to Day 28 | 87.2 % of participants |
| Placebo | Percentage of Participants With Clinical Improvement 1 up to Day 28 | 81.1 % of participants |
Comparison: number of patients included in the analysis=25p-value: 0.07Gray's test
Secondary
Percentage of Participants With Clinical Improvement 2 up to Day 28
Clinical improvement 2 up to Day 28 is defined as cumulative incidence function (CIF, in %). CIF allows for estimation of the occurrence of an event while taking into account the following competing risks: death, reasons for discontinuation for Adverse events and patient transferred to another institution. Estimates are calculated using a nonparametric method. The null hypothesis is that the cumulative incidence functions are identical across treatment groups.
Time frame: At Day 28
Population: FAS Full Analysis Set: set which consisted of all randomized subjects who received at least one dose of the IMP. But FAS patients with at least one major (i.e. error in IMP administration, I/E criteria violation) or minor protocol deviation (i.e. not respecting visit schedule) up to Day 28 couldn't be considered in the analysis.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reparixin | Percentage of Participants With Clinical Improvement 2 up to Day 28 | 69.9 Percentage of patients |
| Placebo | Percentage of Participants With Clinical Improvement 2 up to Day 28 | 67.7 Percentage of patients |
Comparison: Number of patients included in the analysis = 59p-value: 0.668Gray's test
Secondary
Proportion of Patients Alive and Free of Respiratory Failure at Day 60
This key secondary efficacy endpoint of the study is defined as the proportion of patients alive and free of respiratory failure at Day 60, i.e. with no need of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) or admission to intensive care unit (ICU) linked to worsening of respiratory parameters compared to baseline.
Time frame: At day 60
Population: FAS population is used in this table. Discrepancies between the total number of patients in the FAS and patients actually analyzed in the logistic regression model are due to the presence of missing data for which no imputation methods are expected for this endpoint.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reparixin | Proportion of Patients Alive and Free of Respiratory Failure at Day 60 | 141 participants |
| Placebo | Proportion of Patients Alive and Free of Respiratory Failure at Day 60 | 66 participants |
p-value: 0.377Chi-squared
Secondary
Proportion of Patients Alive and Free of Respiratory Failure at Fixed Timepoints
The event variable is defined as the proportion of patients alive and free of respiratory failure at fixed timepoints. This means no need of invasive mechanical ventilation or extracorporeal membrane oxygenation (ECMO) or admission to intensive care unit (ICU) linked to worsening of respiratory parameters compared to baseline. Admissions to ICU had to be considered only in presence of significant worsening of respiratory status. This condition was objectively identified by means of a decrease of PaO2/FiO2 ratio of at least 40% from the baseline value or by a worsening of Investigator's Interpretation.
Time frame: At Days 3, 7(±1),14(±2), 21(±2) and 90(±2) after randomization (randomization = day 1)
Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reparixin | Proportion of Patients Alive and Free of Respiratory Failure at Fixed Timepoints | Day 3 | 179 participants |
| Reparixin | Proportion of Patients Alive and Free of Respiratory Failure at Fixed Timepoints | Day 21 (+/-2) | 155 participants |
| Reparixin | Proportion of Patients Alive and Free of Respiratory Failure at Fixed Timepoints | Day 7 (+/-1) | 171 participants |
| Reparixin | Proportion of Patients Alive and Free of Respiratory Failure at Fixed Timepoints | Day 90 | 15 participants |
| Reparixin | Proportion of Patients Alive and Free of Respiratory Failure at Fixed Timepoints | Day 14 (+/-2) | 160 participants |
| Placebo | Proportion of Patients Alive and Free of Respiratory Failure at Fixed Timepoints | Day 90 | 5 participants |
| Placebo | Proportion of Patients Alive and Free of Respiratory Failure at Fixed Timepoints | Day 7 (+/-1) | 79 participants |
| Placebo | Proportion of Patients Alive and Free of Respiratory Failure at Fixed Timepoints | Day 14 (+/-2) | 73 participants |
| Placebo | Proportion of Patients Alive and Free of Respiratory Failure at Fixed Timepoints | Day 21 (+/-2) | 71 participants |
| Placebo | Proportion of Patients Alive and Free of Respiratory Failure at Fixed Timepoints | Day 3 | 87 participants |
Comparison: At Day 3 - please note that the number of subjects is 268 (180+88) and not 270.p-value: 0.55Fisher Exact
Comparison: At Day 7 - Please note that the total of subjects in this analysis is not 270 but 266 (n=179 in the Reparixin group and n=87 in the placebo group).p-value: 0.128Chi-squared
Comparison: At Day 14 - Please note that the total of subjects in this analysis is not 270 but 256 (n=173 in the Reparixin group and n=83 in the placebo group).p-value: 0.235Chi-squared
Comparison: At Day 21 - Please note that the total of subjects in this analysis is not 270 but 255 (n=172 in the Reparixin group and n=83 in the placebo group).p-value: 0.281Chi-squared
Comparison: At Day 90 - Please note that the total of subjects in this analysis is not 270 but 50 (n=33 in the Reparixin group and n=17 in the placebo group).p-value: 0.273Chi-squared
Secondary
The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints
The number of patients with Dyspnea severity Likert scale by score and treatment group is calculated for each time point. Likert scale: grading the current experience of breathing discomfort compared to baseline (randomization) status (from -3 to 3) where: -1 = minimally worse; -2 = moderately worse; -3 = markedly worse; 0 = no change; 1 = minimally better; 2 = moderately better; 3 = markedly better More negative the score, the worse the outcome.
Time frame: At days 3, 7, 14, 21, 28 and End of Treatment (EoT, up to 30 days); days 60 and 90; at hospital discharge (HD, up to 2 months), and at the EoS (up to 3 months)
Population: FAS Full Analysis Set: set which consisted of all randomized subjects who received at least one dose of the IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 28 score 1 | 7 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 7 score -3 | 1 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 7 score -2 | 0 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 7 score -1 | 0 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 7 score 0 | 9 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 7 score 1 | 19 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 7 score 2 | 31 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 7 score 3 | 36 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 14 score -3 | 0 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 14 score -2 | 2 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 14 score -1 | 0 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 14 score 0 | 9 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 14 score 1 | 6 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 14 score 2 | 18 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 14 score 3 | 41 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 21 score -3 | 1 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 21 score -2 | 0 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 21 score -1 | 0 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 21 score 0 | 6 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 21 score 1 | 9 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 21 score 2 | 9 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 21 score 3 | 35 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | HD score -3 | 0 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | HD score -2 | 0 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | HD score -1 | 0 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | HD score 0 | 2 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | HD score 1 | 3 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | HD score 2 | 5 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | HD score 3 | 28 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 28 score -3 | 0 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 28 score -2 | 0 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 28 score -1 | 0 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 28 score 0 | 9 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 3 score -3 | 1 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 28 score 2 | 9 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 28 score 3 | 48 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | EoT score -3 | 3 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | EoT score -2 | 1 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | EoT score -1 | 0 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | EoT score 0 | 4 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | EoT score 1 | 12 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | EoT score 2 | 17 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | EoT score 3 | 40 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | EOS score -3 | 0 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | EOS score -2 | 0 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | EOS score -1 | 0 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | EOS score 0 | 1 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | EOS score 1 | 1 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | EOS score 2 | 0 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | EOS score 3 | 0 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 3 score -2 | 1 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 3 score -1 | 5 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 3 score 0 | 22 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 3 score 1 | 37 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 3 score 2 | 26 participants |
| Reparixin | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 3 score 3 | 11 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 3 score -3 | 0 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | EoT score 2 | 6 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 3 score -2 | 3 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 21 score 1 | 2 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 3 score -1 | 1 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 28 score -1 | 0 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 3 score 0 | 10 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 21 score 2 | 7 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 3 score 1 | 18 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | HD score 3 | 19 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 3 score 2 | 17 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | EoT score -2 | 0 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 3 score 3 | 3 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 21 score 3 | 20 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 7 score -3 | 0 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 28 score 0 | 3 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 7 score -2 | 1 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | HD score -3 | 0 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 7 score -1 | 1 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | EoT score 1 | 7 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 7 score 0 | 6 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | HD score -2 | 1 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 7 score 1 | 8 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 28 score 1 | 3 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 7 score 2 | 13 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | HD score -1 | 0 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 7 score 3 | 18 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | EoT score -1 | 1 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 14 score -3 | 0 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | HD score 0 | 2 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 14 score -2 | 0 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 28 score 2 | 7 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 14 score -1 | 0 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | HD score 1 | 1 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 14 score 0 | 1 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | EoT score 3 | 24 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 14 score 1 | 6 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | HD score 2 | 4 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 14 score 2 | 7 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 28 score 3 | 20 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 14 score 3 | 25 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | EoT score 0 | 0 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 21 score -3 | 0 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 28 score -3 | 0 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 21 score -2 | 0 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | EoT score -3 | 0 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 21 score -1 | 0 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 28 score -2 | 0 participants |
| Placebo | The Number of Patients With Different Dyspnea Severity Scores Using the Likert Scale at Fixed Timepoints | day 21 score 0 | 3 participants |
Comparison: at day 3 - Please note that the number of subjects in this analysis is not 270 but 155.p-value: 0.997Wilcoxon (Mann-Whitney)
Comparison: at day 7 - Please note that the number of subjects in this analysis is not 270 but 143.p-value: 0.712Wilcoxon (Mann-Whitney)
Comparison: at day 14 - Please note that the number of subjects in this analysis is not 270 but 115.p-value: 0.241Wilcoxon (Mann-Whitney)
Comparison: at day 21 - Please note that the number of subjects in this analysis is not 270 but 92.p-value: 0.528Wilcoxon (Mann-Whitney)
Comparison: at day 28 - Please note that the number of subjects in this analysis is not 270 but 106.p-value: 0.814Wilcoxon (Mann-Whitney)
Comparison: at EOT - Please note that the number of subjects in this analysis is not 270 but 115.p-value: 0.242Wilcoxon (Mann-Whitney)
Comparison: at hospital discharge (HD) - Please note that the number of subjects in this analysis is not 270 but 65.p-value: 0.722Wilcoxon (Mann-Whitney)
Secondary
Time to Discharge From Hospital up to Day 28
Time to discharge from hospital up to Day 28 is analyzed as described for time to recovery.
Time frame: Day 1 (baseline), Days 3, 7, 14, 21, 28
Population: FAS Full Analysis Set: set which consisted of all randomized subjects who received at least one dose of the IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Reparixin | Time to Discharge From Hospital up to Day 28 | Day 1 | 0 number of patients with event |
| Reparixin | Time to Discharge From Hospital up to Day 28 | Day 3 | 2 number of patients with event |
| Reparixin | Time to Discharge From Hospital up to Day 28 | Day 7 | 19 number of patients with event |
| Reparixin | Time to Discharge From Hospital up to Day 28 | Day 14 | 100 number of patients with event |
| Reparixin | Time to Discharge From Hospital up to Day 28 | Day 21 | 127 number of patients with event |
| Reparixin | Time to Discharge From Hospital up to Day 28 | Day 28 | 143 number of patients with event |
| Placebo | Time to Discharge From Hospital up to Day 28 | Day 21 | 58 number of patients with event |
| Placebo | Time to Discharge From Hospital up to Day 28 | Day 1 | 0 number of patients with event |
| Placebo | Time to Discharge From Hospital up to Day 28 | Day 14 | 40 number of patients with event |
| Placebo | Time to Discharge From Hospital up to Day 28 | Day 3 | 0 number of patients with event |
| Placebo | Time to Discharge From Hospital up to Day 28 | Day 28 | 64 number of patients with event |
| Placebo | Time to Discharge From Hospital up to Day 28 | Day 7 | 10 number of patients with event |
Comparison: Estimates are calculated using a nonparametric method for cumulative incidence function with competing risks data. The null hypothesis is that the cumulative incidence functions are identical across treatment groups and estimates are calculated taking into consideration the following competing risks: Reasons for discontinuation for Adverse events and patient transferred to another institution.p-value: 0.23Gray's test
Secondary
Time to Recovery (Category 1 - 2 - 3 of the 7-point WHO Ordinal Scale of Clinical Improvement (WHO-OS)) Until Day 28
This is a key secondary efficacy endpoint. The event recovery was considered as such, if the patient has scored category 1, 2 or 3 from the 7-point WHO Ordinal Scale of clinical improvement (WHO-OS), otherwise it will be considered free of event. Category 1: not hospitalized, with resumption of normal activities; 2: not hospitalized, but unable to resume normal activities; 3: hospitalized, not requiring supplemental oxygen; \[4: hospitalized, requiring supplemental oxygen; 5: hospitalized, requiring high-flow oxygen therapy, non-invasive mechanical ventilation, or both; 6: hospitalized, requiring ECMO, invasive mechanical ventilation, or both; 7: death\]. The lower the category, the better the outcome.
Time frame: Until Day 28
Population: The Full Analysis Set (FAS), which consisted of all randomized subjects who received at least one dose of the IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Reparixin | Time to Recovery (Category 1 - 2 - 3 of the 7-point WHO Ordinal Scale of Clinical Improvement (WHO-OS)) Until Day 28 | 141 number of patients with event (recovery) |
| Placebo | Time to Recovery (Category 1 - 2 - 3 of the 7-point WHO Ordinal Scale of Clinical Improvement (WHO-OS)) Until Day 28 | 63 number of patients with event (recovery) |
Comparison: Until Day 28p-value: 0.167Gray's Test