Acute Respiratory Distress Syndrome
Conditions
Keywords
acute respiratory distress syndrome, ARDS, Adults, Surfactant, Poractant alfa (porcine surfactant, Curosurf®),, Curosurf®, Coronavirus disease (COVID-19), Coronavirus 2019 Disease
Brief summary
The purpose of this study was to evaluate the efficacy and safety of poractant alfa (Curosurf®), administered by endotracheal (ET) instillation in hospitalized adult patients diagnosed with SARS-COV-19 acute respiratory distress syndrome (ARDS).
Detailed description
This was a multicentre, open-label, randomized phase II proof-of-concept study. The efficacy and safety of poractant alfa was evaluated in terms of ventilatory free days during the 21 days after randomization, in adult patients diagnosed with ARDS due to SARS-COV-19 infection. Each patient randomized to the study treatment received 3 administrations of Curosurf ® with a 24 hours dosing interval. The assessment collection was up to Day 28, when the evaluation occurred at the Intensive Care Unit (ICU), or by phone call if the patient has already been discharged. Seventy patients were planned to be randomized in the study with a ratio 3:2 (i.e. 42 patients in the poractant alfa arm and 28 in the control arm). The control arm population received Standard of Care (SoC). This study was conducted in United Kingdom (UK), United States of America (US), and Italy. Overall, 13 patients (Curosurf ® group) and 8 patients (control group) were randomised in the study. Due to low recruitment rate the study was terminated early for non-safety reasons. Curosurf® is a pulmonary surfactant of natural origin which, when delivered endotracheally (ET). Curosurf® is currently approved for marketing as treatment of premature neonates with RDS or at risk of Respiratory Distress Syndrome (RDS). Chiesi Farmaceutici S.p.A (Chiesi) conducted this study with its porcine-derived surfactant, Curosurf® (poractant alfa), to evaluate the efficacy and safety in ventilated adult patients who were critically unwell in intensive care with SARS-COV-19 ARDS.
Interventions
DRUGCUROSURF® (poractant alfa)
Three administrations with a 24 hours dosing interval. Each endotracheal (ET) administration 1, 2, and 3 consisted of poractant alfa bolus: 30mg /kg (Lean Body Weight-LBW) = 0.375ml /kg LBW, diluted with normal saline up to 2ml /kg LBW.
Sponsors
Chiesi Farmaceutici S.p.A.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Seventy patients will be randomized in the study with a ratio 3:2 (i.e. 42 patients in the poractant alfa arm and 28 in the control arm).
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
Participants were eligible to be included in the study if the following criteria apply: 1. Male or female ≥18 and ≤ 80 years of age 2. Informed consent for participation in the study (refer to section 15 for detailed inform consent procedure) 3. Positive 2019-nCoV Reverse Transcription Polymerase Chain Reaction (rt-PCR) before randomisation 4. Arterial Partial Pressure of Oxygen/Fraction of Inspired Oxygen (PaO2/FiO2) ratio \< 150 mmHg 5. Lung compliance ≤45 ml/cmH20 6. Intubated and artificially ventilated less than 48 hours before the first poractant alfa administration
Exclusion criteria
Participants were excluded from the study if any of the following criteria apply: 1. Any contraindications to surfactant administration e.g., pulmonary hemorrhage and pneumothorax) 2. Weight \< 40kg 3. Stage 4 severe chronic kidney disease (i.e., Estimated Glomerular Filtration Rate (eGFR) \< 30) 4. Pregnancy 5. Administration of any nebulized surfactant in the 48 hours before the first poractant alfa administration 6. Extracorporeal membrane oxygenation (ECMO)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Days Alive and Ventilator-free Days | up to 21 days | The number of days alive and ventilator-free days, defined as the number of days the patient is not receiving mechanical ventilation over the 21 days following randomisation. Mechanical ventilation was defined as invasive and non-invasive. The patient was defined as free of mechanical ventilation after 12 hours from the suspension of either invasive and non-invasive ventilation. Patients who died or were mechanically ventilated longer than this period were assessed as zero ventilator-free days. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Days Alive and Ventilator-Free at Day 28 | at Day 28 | The number of days alive and ventilator-free (i.e. free of any mechanical ventilation for at least 12 hours) at Day 28. |
| Mortality at Day 21 and Day 28 | at Day 21 and at Day 28 | Mortality at Day 21 and Day 28 of the study by treatment group. |
| Number of Days Alive and Free From Invasive Ventilation at Day 21 and Day 28 | Day 21 and Day 28 | The number of days alive and free from invasive ventilation at Day 21 and Day 28 is presented by treatment group. |
| Number of Days Alive and Free From Non-Invasive Ventilation at Day 21 and Day 28 | Day 21 and Day 28 | The number of days alive and free from non-invasive ventilation at Day 21 and Day 28 is presented by treatment group. |
| Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28 | Ventilatory parameter: Change from baseline in dynamic compliance (mL/cmH2O) at all timepoints up to Day 3 (72 hours) and at Day 28. The change was calculated from two time points as the value at the later time point minus the value at baseline. Dynamic compliance: is the continuous measurement of pulmonary compliance calculated at each point representing schematic changes during rhythmic breathing. Dynamic compliance monitors both elastic and airway resistance. |
| Percentage of Patients With Improvement in Severity Status at Day 28 or Discharge (Severity Score: Mild, Moderate, Severe, or Death) | Day 28 or Discharge, whichever comes first | The severity status of patients at baseline and at Day 28/Discharge and the percentage of patients with improvement in severity status (i.e. a decrease of at least 1 point in severity status) at Day 28/Discharge relative to baseline is presented. Severity was assessed using a point score system: Severity score was defined as mild, moderate, severe (see below\*), or death and was based on PaO2/FiO2 ratio and patient status at Day 28/Discharge and numerically rated from 1-4, respectively. An improvement in severity was defined as a decrease of at least 1 point between baseline and Day 28/Discharge. At Day 28 the last follow up evaluation took place on the ICU if, still requiring critical care, or by phone call if the patient has been discharged from ICU by that time. \*Mild: 200 mmHg \< PaO2/FiO2 ratio ≤300 mmHg; Moderate: 100 mmHg \< PaO2/FiO2 ratio ≤200 mmHg; Severe: PaO2/FiO2 ratio ≤100 mmHg |
| Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint | up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28 | Change from baseline in PaO2/FiO2 ratio measured at each timepoint following administration of each dose in the treatment and control group. The change was calculated from two time points as the value at the later time point minus the value at baseline. Partial pressure of oxygen (PaO2) is the oxygen pressure in arterial blood. The fraction of inspired oxygen (FiO2) is the concentration of oxygen in the gas mixture. The fraction of inspired oxygen (PaO2/FiO2) ratio is widely used in ICUs as an indicator of oxygenation status. |
| Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint | up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28 | The percentages of patients in categories of PaO2/FiO2 ratio improvement compared to baseline (\>20%) at all timepoints post-baseline are summarised by treatment group. |
| Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint | up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28 | The FiO2 at baseline and at selected timepoints post-baseline was measured. Results are shown as changes from baseline, summarised by treatment group. The change was calculated from two time points as the value at the later time point minus the value at baseline. The unit for the variable is percent (%) and what is reported is an absolute change. |
| Length of ICU Stay (Days) at Day 28 | up to 28 days | The length of ICU stay (days) at Day 28 is presented by treatment by treatment group. Patients who died or were mechanically ventilated longer than this period were assigned with 28 days. |
| Percentage of Patients Alive and Out of Intensive Care Unit (ICU) at Day 28 | Day 28 | The percentage of patients alive and out of ICU at Day 28 is presented by treatment group. |
| Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Day 3 and Day 28 or discharge -- whichever comes first | The Sequential Organ Failure Assessment (SOFA) score is a scoring system that assesses the performance of several organ systems in the body. The SOFA score was used to determine the extent of organ failure at Day 3 and Day 28/Discharge with respect to a pre-randomisation assessment. The total score was derived from six sub-scores system categories: respiratory, neurological, cardiovascular, hepatic, coagulation, and renal systems; respective sub-scores were calculated primarily considering PaO2/FiO2 ratio, Glasgow Coma Scale, mean arterial pressure (MAP) or requirement for vasopressor administration, bilirubin levels, platelet levels and creatinine levels or daily urine output. A score of 0, 1, 2, 3, or 4) was assigned to each of the six system category. The total score ranged from 0 (min) to 24 (max) points. To be considered organ failure free, a patient had to have a score of 0. |
| Percentage of Patients Alive and Free of Respiratory Failure at Day 28 | at Day 28 | The percentage of patients alive and free of respiratory failure (i.e. without need for mechanical ventilation, extracorporeal membrane oxygenation (ECMO), non-invasive ventilation, or high-flow nasal cannula oxygen delivery) at Day 28. |
| Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28 | Ventilatory parameter: Change from baseline in tidal volume (mL/kg BW) at all timepoints up to Day 3 (72 hours) and at Day 28. The change was calculated from two time points as the value at the later time point minus the value at baseline. Tidal volume is the amount of air that moves in or out of the lungs with each respiratory cycle. |
| Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28 | Ventilatory parameter: Change from baseline in respiratory rate (breaths/minute) at all timepoints up to Day 3 (72 hours) and at Day 28. The change was calculated from two time points as the value at the later time point minus the value at baseline. Respiratory rate is the number of breaths taken per minute. |
| Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28 | Ventilatory parameter: static compliance -- change from baseline in static compliance (mL/cmH2O) at all timepoints up to Day 3 (72 hours) and at Day 28. The change was calculated from two time points as the value at the later time point minus the value at baseline. At each time point the number of patients that contributed with a result value is indicated for both study arms. Static Compliance: represents pulmonary compliance at a given fixed volume when there is no airflow, and muscles are relaxed. |
| Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28 | Ventilatory parameter: Positive End-Expiratory Pressure -- Change from baseline in PEEP (cmH2O) at all timepoints up to Day 3 (72 hours) and at Day 28. The change was calculated from two time points as the value at the later time point minus the value at baseline. At each time point the number of patients that contributed with a result value is indicated for both study arms. Positive end-expiratory pressure (PEEP) is the positive pressure that will remain in the airways at the end of the respiratory cycle (end of exhalation) that is greater than the atmospheric pressure in mechanically ventilated patients. |
| Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28 | Ventilatory parameter: Peak Inspiratory Pressure -- Change from baseline in peak inspiratory pressure (cmH2O) at all timepoints up to Day 3 (72 hours) and at Day 28. The change was calculated from two time points as the value at the later time point minus the value at baseline. At each time point the number of patients that contributed with a result value is indicated for both study arms. Peak inspiratory pressure (PIP) is the highest level of pressure applied to the lungs during inhalation. In mechanical ventilation the number reflects a positive pressure in centimetres of water pressure (cmH2O). |
| Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28 | Ventilatory parameter: Plateau Pressure -- Change from baseline in plateau pressure (cmH2O) at all timepoints up to Day 3 (72 hours) and at Day 28. The change was calculated from two time points as the value at the later time point minus the value at baseline. At each time point the number of patients that contributed with a result value is indicated for both study arms. Plateau pressure is the pressure that is applied by the mechanical ventilator to the small airways and alveoli. |
| Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH | up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28 | Change from baseline in blood gas analysis acid-base balance parameters -- pH. The change was calculated from two time points as the value at the later time point minus the value at baseline. Arterial blood gas was measured at 6, 12, 24, 30, 36, 48, 54, 60 and 72 hours after randomisation and up to Day 28 or till the patient was discharged from the ICU - whichever occurred earlier. |
| Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) | up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28 | Change from baseline in blood gas analysis acid-base balance parameter -- pCO2. The change was calculated from two time points as the value at the later time point minus the value at baseline. Arterial blood gas was measured at 6, 12, 24, 30, 36, 48, 54, 60 and 72 hours after randomisation and up to Day 28 or till the patient was discharged from the ICU - whichever occurred earlier. |
| Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) | up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28 | Change from baseline in blood gas analysis acid-base balance parameter -- pO2. The change was calculated from two time points as the value at the later time point minus the value at baseline. Arterial blood gas was measured at 6, 12, 24, 30, 36, 48, 54, 60 and 72 hours after randomisation and up to Day 28 or till the patient was discharged from the ICU - whichever occurred earlier. |
| Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) | up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28 | Change from baseline in blood gas analysis acid-base balance parameter -- Bicarbonate (HCO3). The change was calculated from two time points as the value at the later time point minus the value at baseline. Measured at 6-12-24h after each poractant alfa administration up to 72 hours and at similar timepoints in the control group (6, 12, 24, 30, 36, 48, 54, 60 and 72 hours after randomisation) and then every 24 hours till the patient is discharged from the ICU |
| Change From Baseline in Blood Parameter -- Lactate | up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28 | Change from baseline in blood parameter -- Lactate The change was calculated from two time points as the value at the later time point minus the value at baseline. At each time point the number of patients that contributed with a result value is indicated for both study arms. Arterial blood lactate was measured at 6, 12, 24, 30, 36, 48, 54, 60, and 72 hours after randomisation and up to Day 28 or till the patient was discharged from the ICU - whichever occurred earlier. |
| Mortality -- TEAEs Leading to Death | up to day 28 | The incidence of treatment-emergent adverse event (TEAEs) leading to death is presented by treatment group. |
| Percentage of Patients Alive and Free of Organ Failure (SOFA Score=0) | at day 28 or discharge -- whichever comes first | The percentage of patients alive and organ failure free (defined as SOFA score=0) at Day 28/Discharge is presented by treatment group. The total score was derived from six sub-scores system categories: respiratory, neurological, cardiovascular, hepatic, coagulation, and renal systems; respective sub-scores were calculated primarily considering PaO2/FiO2 ratio, Glasgow Coma Scale, mean arterial pressure (MAP) or requirement for vasopressor administration, bilirubin levels, platelet levels and creatinine levels or daily urine output. A score of 0, 1, 2, 3, or 4) was assigned to each of the six system category. The total score ranged from 0 (min) to 24 (max) points. To be considered organ failure free, a patient had to have a score of 0. |
Countries
Italy, United Kingdom, United States
Participant flow
Recruitment details
The planned 70 randomised patients in a 3:2 ratio, according to the inclusion and exclusion criteria. This was not achieved; owing to a global improvement in the pandemic situation in the countries where the study was performed (Italy, UK, US), patient recruitment was lower than expected (i.e. 22 patients were randomised, 14 patients and 8 patients in the poractant alfa and control groups, respectively); the study was terminated early before reaching the target sample size.
Participants by arm
| Arm | Count |
|---|---|
| Control Cohort Patients receiving SoC | 8 |
| Poractant Alfa Treated Cohort Patients treated with CUROSURF® (poractant alfa), as an add-on to standard-of-care (SoC) | 13 |
| Total | 21 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Death | 2 | 4 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Physician Decision | 0 | 1 |
Baseline characteristics
| Characteristic | Poractant Alfa Treated Cohort | Total | Control Cohort |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 6 Participants | 9 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 7 Participants | 12 Participants | 5 Participants |
| Age, Continuous | 63.6 years STANDARD_DEVIATION 9.2 | 58.8 years STANDARD_DEVIATION 14.4 | 51.0 years STANDARD_DEVIATION 18.2 |
| Arterial Partial Pressure of Oxygen/Fraction of inspired oxygen (PaO2/FiO2) ratio | 111.85 Ratio STANDARD_DEVIATION 38.72 | 111.03 Ratio STANDARD_DEVIATION 42.62 | 109.70 Ratio STANDARD_DEVIATION 51.15 |
| Body mass index (BMI) | 29.78 kg/m^2 STANDARD_DEVIATION 5.05 | 32.32 kg/m^2 STANDARD_DEVIATION 7.78 | 36.44 kg/m^2 STANDARD_DEVIATION 9.9 |
| Fraction of inspired oxygen (FiO2) | 65.0 percentage of inspired oxygen STANDARD_DEVIATION 23.2 | 67.1 percentage of inspired oxygen STANDARD_DEVIATION 21.1 | 70.5 percentage of inspired oxygen STANDARD_DEVIATION 18.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 1 Participants | 2 Participants | 1 Participants |
| Race (NIH/OMB) White | 12 Participants | 18 Participants | 6 Participants |
| Sequential Organ Failure Assessment (SOFA) score | 7.8 score STANDARD_DEVIATION 4.6 | 7.5 score STANDARD_DEVIATION 4.2 | 7.0 score STANDARD_DEVIATION 3.5 |
| Sex: Female, Male Female | 3 Participants | 5 Participants | 2 Participants |
| Sex: Female, Male Male | 10 Participants | 16 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 2 / 8 | 4 / 13 |
| other Total, other adverse events | 5 / 8 | 11 / 13 |
| serious Total, serious adverse events | 3 / 8 | 5 / 13 |
Outcome results
Primary
Number of Days Alive and Ventilator-free Days
The number of days alive and ventilator-free days, defined as the number of days the patient is not receiving mechanical ventilation over the 21 days following randomisation. Mechanical ventilation was defined as invasive and non-invasive. The patient was defined as free of mechanical ventilation after 12 hours from the suspension of either invasive and non-invasive ventilation. Patients who died or were mechanically ventilated longer than this period were assessed as zero ventilator-free days.
Time frame: up to 21 days
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics.~Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Cohort | Number of Days Alive and Ventilator-free Days | 4.8 days | Standard Deviation 6.6 |
| Poractant Alfa Treated Cohort | Number of Days Alive and Ventilator-free Days | 1.2 days | Standard Deviation 4.2 |
Secondary
Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH
Change from baseline in blood gas analysis acid-base balance parameters -- pH. The change was calculated from two time points as the value at the later time point minus the value at baseline. Arterial blood gas was measured at 6, 12, 24, 30, 36, 48, 54, 60 and 72 hours after randomisation and up to Day 28 or till the patient was discharged from the ICU - whichever occurred earlier.
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control Cohort | Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH | 48 hours | 0.0050 pH |
| Control Cohort | Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH | 54 hours | 0.0500 pH |
| Control Cohort | Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH | 12 hours | 0.0050 pH |
| Control Cohort | Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH | 60 hours | -0.0500 pH |
| Control Cohort | Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH | 30 hours | 0.0300 pH |
| Control Cohort | Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH | 72 hours | 0.0400 pH |
| Control Cohort | Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH | 6 hours | 0.0000 pH |
| Control Cohort | Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH | 28 day | -0.0400 pH |
| Control Cohort | Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH | 36 hours | 0.0050 pH |
| Control Cohort | Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH | 24 hours | 0.0315 pH |
| Poractant Alfa Treated Cohort | Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH | 48 hours | 0.0300 pH |
| Poractant Alfa Treated Cohort | Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH | ICU Discharge | 0.0450 pH |
| Poractant Alfa Treated Cohort | Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH | 6 hours | 0.0080 pH |
| Poractant Alfa Treated Cohort | Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH | 12 hours | 0.0100 pH |
| Poractant Alfa Treated Cohort | Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH | 24 hours | 0.0160 pH |
| Poractant Alfa Treated Cohort | Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH | 30 hours | 0.0100 pH |
| Poractant Alfa Treated Cohort | Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH | 36 hours | 0.0260 pH |
| Poractant Alfa Treated Cohort | Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH | 54 hours | 0.0185 pH |
| Poractant Alfa Treated Cohort | Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH | 60 hours | 0.0000 pH |
| Poractant Alfa Treated Cohort | Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH | 72 hours | 0.0120 pH |
| Poractant Alfa Treated Cohort | Blood Gas Analysis Acid-base Balance Parameters: Change From Baseline in Blood Gas Analysis Acid-base Balance Parameters -- pH | 28 day | 0.0500 pH |
Secondary
Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint
Change from baseline in PaO2/FiO2 ratio measured at each timepoint following administration of each dose in the treatment and control group. The change was calculated from two time points as the value at the later time point minus the value at baseline. Partial pressure of oxygen (PaO2) is the oxygen pressure in arterial blood. The fraction of inspired oxygen (FiO2) is the concentration of oxygen in the gas mixture. The fraction of inspired oxygen (PaO2/FiO2) ratio is widely used in ICUs as an indicator of oxygenation status.
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.~At each time point the number of patients that contributed with a result value is indicated for both study arms.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control Cohort | Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint | 6 hours | 7.00 mmHg |
| Control Cohort | Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint | 12 hours | 23.00 mmHg |
| Control Cohort | Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint | 24 hours | 31.00 mmHg |
| Control Cohort | Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint | 30 hours | 70.00 mmHg |
| Control Cohort | Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint | 36 hours | 11.00 mmHg |
| Control Cohort | Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint | 48 hours | 24.00 mmHg |
| Control Cohort | Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint | 54 hours | 78.00 mmHg |
| Control Cohort | Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint | 60 hours | 0.00 mmHg |
| Control Cohort | Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint | 72 hours | -1.40 mmHg |
| Control Cohort | Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint | 28 day | 53.50 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint | 36 hours | 31.00 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint | 6 hours | 13.00 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint | 72 hours | -1.00 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint | 12 hours | 10.01 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint | 48 hours | 15.65 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint | 24 hours | 2.36 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint | 60 hours | 7.00 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint | 30 hours | 10.00 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint | 28 day | 20.00 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Arterial Partial Pressure of Oxygen / Fraction of Inspired Oxygen (PaO2/FiO2) Ratio at Each Timepoint | 54 hours | 25.07 mmHg |
Secondary
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3)
Change from baseline in blood gas analysis acid-base balance parameter -- Bicarbonate (HCO3). The change was calculated from two time points as the value at the later time point minus the value at baseline. Measured at 6-12-24h after each poractant alfa administration up to 72 hours and at similar timepoints in the control group (6, 12, 24, 30, 36, 48, 54, 60 and 72 hours after randomisation) and then every 24 hours till the patient is discharged from the ICU
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) | 48 hours | 1.60 mmol/L |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) | 12 hours | 1.10 mmol/L |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) | 54 hours | 0.80 mmol/L |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) | 30 hours | 2.30 mmol/L |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) | 60 hours | 3.30 mmol/L |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) | 72 hours | 3.00 mmol/L |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) | 6 hours | 1.05 mmol/L |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) | 28 day | 1.90 mmol/L |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) | 36 hours | 1.75 mmol/L |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) | 24 hours | 1.65 mmol/L |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) | 60 hours | 2.80 mmol/L |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) | ICU Discharge | -3.90 mmol/L |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) | 6 hours | 0.70 mmol/L |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) | 12 hours | 1.30 mmol/L |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) | 24 hours | 1.80 mmol/L |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) | 30 hours | 2.30 mmol/L |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) | 36 hours | 2.70 mmol/L |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) | 48 hours | 3.50 mmol/L |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) | 54 hours | 2.10 mmol/L |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) | 72 hours | 4.00 mmol/L |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Bicarbonate (HCO3) | 28 day | 13.20 mmol/L |
Secondary
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2)
Change from baseline in blood gas analysis acid-base balance parameter -- pCO2. The change was calculated from two time points as the value at the later time point minus the value at baseline. Arterial blood gas was measured at 6, 12, 24, 30, 36, 48, 54, 60 and 72 hours after randomisation and up to Day 28 or till the patient was discharged from the ICU - whichever occurred earlier.
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) | 54 hours | -0.600 mmHg |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) | 60 hours | 3.400 mmHg |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) | 72 hours | 0.000 mmHg |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) | 28 day | 6.150 mmHg |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) | 6 hours | -2.210 mmHg |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) | 12 hours | -0.150 mmHg |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) | 24 hours | -2.610 mmHg |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) | 30 hours | -5.700 mmHg |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) | 36 hours | -3.350 mmHg |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) | 48 hours | 2.500 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) | 48 hours | 0.300 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) | 12 hours | 1.730 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) | 36 hours | 1.720 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) | 60 hours | -0.230 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) | 24 hours | -2.000 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) | 72 hours | 0.750 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) | 54 hours | -1.500 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) | 28 day | 12.000 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) | ICU Discharge | -9.600 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) | 30 hours | 1.880 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Carbon Dioxide (pCO2) | 6 hours | 1.535 mmHg |
Secondary
Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2)
Change from baseline in blood gas analysis acid-base balance parameter -- pO2. The change was calculated from two time points as the value at the later time point minus the value at baseline. Arterial blood gas was measured at 6, 12, 24, 30, 36, 48, 54, 60 and 72 hours after randomisation and up to Day 28 or till the patient was discharged from the ICU - whichever occurred earlier.
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) | 24 hours | 7.000 mmHg |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) | 6 hours | 0.500 mmHg |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) | 30 hours | 3.000 mmHg |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) | 72 hours | 6.000 mmHg |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) | 36 hours | 7.000 mmHg |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) | 12 hours | 12.500 mmHg |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) | 48 hours | 6.250 mmHg |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) | 28 day | 8.100 mmHg |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) | 54 hours | 4.300 mmHg |
| Control Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) | 60 hours | 15.000 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) | 48 hours | 0.000 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) | 54 hours | 2.250 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) | 60 hours | 0.000 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) | 72 hours | 5.100 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) | 28 day | -7.700 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) | ICU Discharge | -10.730 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) | 6 hours | 6.550 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) | 12 hours | 1.000 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) | 24 hours | 1.100 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) | 30 hours | 2.000 mmHg |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Gas Analysis Acid-base Balance Parameter -- Partial Pressure of Oxygen (pO2) | 36 hours | 2.600 mmHg |
Secondary
Change From Baseline in Blood Parameter -- Lactate
Change from baseline in blood parameter -- Lactate The change was calculated from two time points as the value at the later time point minus the value at baseline. At each time point the number of patients that contributed with a result value is indicated for both study arms. Arterial blood lactate was measured at 6, 12, 24, 30, 36, 48, 54, 60, and 72 hours after randomisation and up to Day 28 or till the patient was discharged from the ICU - whichever occurred earlier.
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control Cohort | Change From Baseline in Blood Parameter -- Lactate | 48 hours | -0.10 mmol/L |
| Control Cohort | Change From Baseline in Blood Parameter -- Lactate | 24 hours | -0.10 mmol/L |
| Control Cohort | Change From Baseline in Blood Parameter -- Lactate | 54 hours | 0.25 mmol/L |
| Control Cohort | Change From Baseline in Blood Parameter -- Lactate | 12 hours | 0.55 mmol/L |
| Control Cohort | Change From Baseline in Blood Parameter -- Lactate | 60 hours | 0.10 mmol/L |
| Control Cohort | Change From Baseline in Blood Parameter -- Lactate | 30 hours | 0.30 mmol/L |
| Control Cohort | Change From Baseline in Blood Parameter -- Lactate | 72 hours | -0.20 mmol/L |
| Control Cohort | Change From Baseline in Blood Parameter -- Lactate | 6 hours | 0.05 mmol/L |
| Control Cohort | Change From Baseline in Blood Parameter -- Lactate | 28 day | -0.60 mmol/L |
| Control Cohort | Change From Baseline in Blood Parameter -- Lactate | 36 hours | 0.55 mmol/L |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Parameter -- Lactate | 36 hours | -0.10 mmol/L |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Parameter -- Lactate | 28 day | -0.10 mmol/L |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Parameter -- Lactate | ICU Discharge | -2.30 mmol/L |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Parameter -- Lactate | 6 hours | -0.05 mmol/L |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Parameter -- Lactate | 12 hours | 0.20 mmol/L |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Parameter -- Lactate | 24 hours | -0.10 mmol/L |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Parameter -- Lactate | 30 hours | 0.00 mmol/L |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Parameter -- Lactate | 48 hours | -0.10 mmol/L |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Parameter -- Lactate | 54 hours | 0.00 mmol/L |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Parameter -- Lactate | 60 hours | -0.10 mmol/L |
| Poractant Alfa Treated Cohort | Change From Baseline in Blood Parameter -- Lactate | 72 hours | -0.10 mmol/L |
Secondary
Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint
The FiO2 at baseline and at selected timepoints post-baseline was measured. Results are shown as changes from baseline, summarised by treatment group. The change was calculated from two time points as the value at the later time point minus the value at baseline. The unit for the variable is percent (%) and what is reported is an absolute change.
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control Cohort | Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint | 24 hours | 0.0 percent (absolute change) |
| Control Cohort | Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint | 30 hours | -15.0 percent (absolute change) |
| Control Cohort | Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint | 36 hours | -10.0 percent (absolute change) |
| Control Cohort | Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint | 6 hours | -7.2 percent (absolute change) |
| Control Cohort | Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint | 12 hours | -2.5 percent (absolute change) |
| Control Cohort | Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint | 48 hours | -12.5 percent (absolute change) |
| Control Cohort | Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint | 54 hours | -12.5 percent (absolute change) |
| Control Cohort | Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint | 60 hours | 2.5 percent (absolute change) |
| Control Cohort | Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint | 72 hours | -4.9 percent (absolute change) |
| Control Cohort | Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint | 28 day | -14.3 percent (absolute change) |
| Poractant Alfa Treated Cohort | Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint | 60 hours | -5.0 percent (absolute change) |
| Poractant Alfa Treated Cohort | Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint | 24 hours | 0.0 percent (absolute change) |
| Poractant Alfa Treated Cohort | Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint | 48 hours | 0.0 percent (absolute change) |
| Poractant Alfa Treated Cohort | Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint | 30 hours | -5.0 percent (absolute change) |
| Poractant Alfa Treated Cohort | Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint | 28 day | -7.5 percent (absolute change) |
| Poractant Alfa Treated Cohort | Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint | 54 hours | -5.0 percent (absolute change) |
| Poractant Alfa Treated Cohort | Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint | 6 hours | 0.0 percent (absolute change) |
| Poractant Alfa Treated Cohort | Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint | 72 hours | 0.0 percent (absolute change) |
| Poractant Alfa Treated Cohort | Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint | 12 hours | -5.0 percent (absolute change) |
| Poractant Alfa Treated Cohort | Change From Baseline in Fraction of Inspired Oxygen (FiO2) at Each Timepoint | 36 hours | -10.0 percent (absolute change) |
Secondary
Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28
The Sequential Organ Failure Assessment (SOFA) score is a scoring system that assesses the performance of several organ systems in the body. The SOFA score was used to determine the extent of organ failure at Day 3 and Day 28/Discharge with respect to a pre-randomisation assessment. The total score was derived from six sub-scores system categories: respiratory, neurological, cardiovascular, hepatic, coagulation, and renal systems; respective sub-scores were calculated primarily considering PaO2/FiO2 ratio, Glasgow Coma Scale, mean arterial pressure (MAP) or requirement for vasopressor administration, bilirubin levels, platelet levels and creatinine levels or daily urine output. A score of 0, 1, 2, 3, or 4) was assigned to each of the six system category. The total score ranged from 0 (min) to 24 (max) points. To be considered organ failure free, a patient had to have a score of 0.
Time frame: Day 3 and Day 28 or discharge -- whichever comes first
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | SOFA score -- Day 28 / Discharge | -1.0 score on a scale |
| Control Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Coagulatory system score -- Day 3 | 0.0 score on a scale |
| Control Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Respiratory system score -- Day 3 | 0.0 score on a scale |
| Control Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Hepatic system score -- Day 3 | 0.0 score on a scale |
| Control Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Respiratory system score -- Day 28 / Discharge | -1.0 score on a scale |
| Control Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Hepatic system score -- Day 28 / Discharge | 0.0 score on a scale |
| Control Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Neurological system score -- Day 3 | 0.0 score on a scale |
| Control Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Renal system score -- Day 3 | 0.0 score on a scale |
| Control Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Neurological system score -- Day 28 / Discharge | -2.0 score on a scale |
| Control Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Renal system score -- Day 28 / Discharge | 0.0 score on a scale |
| Control Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Cardiovascular system score -- Day 3 | 0.0 score on a scale |
| Control Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | SOFA score -- Day 3 | 0.5 score on a scale |
| Control Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Cardiovascular system score -- Day 28 / Discharge | 0.0 score on a scale |
| Control Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Coagulatory system score -- Day 28 / Discharge | 0.0 score on a scale |
| Poractant Alfa Treated Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Cardiovascular system score -- Day 28 / Discharge | 0.0 score on a scale |
| Poractant Alfa Treated Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Hepatic system score -- Day 3 | 0.0 score on a scale |
| Poractant Alfa Treated Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Hepatic system score -- Day 28 / Discharge | 0.0 score on a scale |
| Poractant Alfa Treated Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Coagulatory system score -- Day 3 | 0.0 score on a scale |
| Poractant Alfa Treated Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Coagulatory system score -- Day 28 / Discharge | 0.0 score on a scale |
| Poractant Alfa Treated Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Renal system score -- Day 3 | 0.0 score on a scale |
| Poractant Alfa Treated Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | SOFA score -- Day 3 | 0.0 score on a scale |
| Poractant Alfa Treated Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | SOFA score -- Day 28 / Discharge | 0.0 score on a scale |
| Poractant Alfa Treated Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Respiratory system score -- Day 3 | 0.0 score on a scale |
| Poractant Alfa Treated Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Respiratory system score -- Day 28 / Discharge | -0.5 score on a scale |
| Poractant Alfa Treated Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Neurological system score -- Day 3 | 0.0 score on a scale |
| Poractant Alfa Treated Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Neurological system score -- Day 28 / Discharge | 0.0 score on a scale |
| Poractant Alfa Treated Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Cardiovascular system score -- Day 3 | 0.0 score on a scale |
| Poractant Alfa Treated Cohort | Delta Sequential Organ Failure Assessment (SOFA) Score and Sub-component Measure at Day 3 and Day 28 | Renal system score -- Day 28 / Discharge | 0.0 score on a scale |
Secondary
Length of ICU Stay (Days) at Day 28
The length of ICU stay (days) at Day 28 is presented by treatment by treatment group. Patients who died or were mechanically ventilated longer than this period were assigned with 28 days.
Time frame: up to 28 days
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Control Cohort | Length of ICU Stay (Days) at Day 28 | 28.0 days |
| Poractant Alfa Treated Cohort | Length of ICU Stay (Days) at Day 28 | 28.0 days |
Secondary
Mortality at Day 21 and Day 28
Mortality at Day 21 and Day 28 of the study by treatment group.
Time frame: at Day 21 and at Day 28
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Control Cohort | Mortality at Day 21 and Day 28 | Dead at Day 21 | 2 Participants |
| Control Cohort | Mortality at Day 21 and Day 28 | Dead at Day 28 | 2 Participants |
| Poractant Alfa Treated Cohort | Mortality at Day 21 and Day 28 | Dead at Day 21 | 4 Participants |
| Poractant Alfa Treated Cohort | Mortality at Day 21 and Day 28 | Dead at Day 28 | 4 Participants |
Secondary
Mortality -- TEAEs Leading to Death
The incidence of treatment-emergent adverse event (TEAEs) leading to death is presented by treatment group.
Time frame: up to day 28
Population: Safety Population: all randomised patients (who received at least one dose of the study treatment if poractant alfa-treated).
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Control Cohort | Mortality -- TEAEs Leading to Death | 2 Participants |
| Poractant Alfa Treated Cohort | Mortality -- TEAEs Leading to Death | 3 Participants |
Secondary
Number of Days Alive and Free From Invasive Ventilation at Day 21 and Day 28
The number of days alive and free from invasive ventilation at Day 21 and Day 28 is presented by treatment group.
Time frame: Day 21 and Day 28
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control Cohort | Number of Days Alive and Free From Invasive Ventilation at Day 21 and Day 28 | Days alive and free from invasive ventilation at Day 21 | 0 days |
| Control Cohort | Number of Days Alive and Free From Invasive Ventilation at Day 21 and Day 28 | Days alive and free from invasive ventilation at Day 28 | 0 days |
| Poractant Alfa Treated Cohort | Number of Days Alive and Free From Invasive Ventilation at Day 21 and Day 28 | Days alive and free from invasive ventilation at Day 21 | 0 days |
| Poractant Alfa Treated Cohort | Number of Days Alive and Free From Invasive Ventilation at Day 21 and Day 28 | Days alive and free from invasive ventilation at Day 28 | 0 days |
Secondary
Number of Days Alive and Free From Non-Invasive Ventilation at Day 21 and Day 28
The number of days alive and free from non-invasive ventilation at Day 21 and Day 28 is presented by treatment group.
Time frame: Day 21 and Day 28
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control Cohort | Number of Days Alive and Free From Non-Invasive Ventilation at Day 21 and Day 28 | Days alive and free from non-invasive ventilation at Day 21 | 12.5 days |
| Control Cohort | Number of Days Alive and Free From Non-Invasive Ventilation at Day 21 and Day 28 | Days alive and free from non-invasive ventilation at Day 28 | 19.5 days |
| Poractant Alfa Treated Cohort | Number of Days Alive and Free From Non-Invasive Ventilation at Day 21 and Day 28 | Days alive and free from non-invasive ventilation at Day 21 | 21.0 days |
| Poractant Alfa Treated Cohort | Number of Days Alive and Free From Non-Invasive Ventilation at Day 21 and Day 28 | Days alive and free from non-invasive ventilation at Day 28 | 28.0 days |
Secondary
Number of Days Alive and Ventilator-Free at Day 28
The number of days alive and ventilator-free (i.e. free of any mechanical ventilation for at least 12 hours) at Day 28.
Time frame: at Day 28
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Control Cohort | Number of Days Alive and Ventilator-Free at Day 28 | 7.4 days | Standard Deviation 10.2 |
| Poractant Alfa Treated Cohort | Number of Days Alive and Ventilator-Free at Day 28 | 1.7 days | Standard Deviation 6.1 |
Secondary
Percentage of Patients Alive and Free of Organ Failure (SOFA Score=0)
The percentage of patients alive and organ failure free (defined as SOFA score=0) at Day 28/Discharge is presented by treatment group. The total score was derived from six sub-scores system categories: respiratory, neurological, cardiovascular, hepatic, coagulation, and renal systems; respective sub-scores were calculated primarily considering PaO2/FiO2 ratio, Glasgow Coma Scale, mean arterial pressure (MAP) or requirement for vasopressor administration, bilirubin levels, platelet levels and creatinine levels or daily urine output. A score of 0, 1, 2, 3, or 4) was assigned to each of the six system category. The total score ranged from 0 (min) to 24 (max) points. To be considered organ failure free, a patient had to have a score of 0.
Time frame: at day 28 or discharge -- whichever comes first
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Cohort | Percentage of Patients Alive and Free of Organ Failure (SOFA Score=0) | 0 percentage of participants |
| Poractant Alfa Treated Cohort | Percentage of Patients Alive and Free of Organ Failure (SOFA Score=0) | 0 percentage of participants |
Secondary
Percentage of Patients Alive and Free of Respiratory Failure at Day 28
The percentage of patients alive and free of respiratory failure (i.e. without need for mechanical ventilation, extracorporeal membrane oxygenation (ECMO), non-invasive ventilation, or high-flow nasal cannula oxygen delivery) at Day 28.
Time frame: at Day 28
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics.~Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Cohort | Percentage of Patients Alive and Free of Respiratory Failure at Day 28 | 25.0 percentage of participants |
| Poractant Alfa Treated Cohort | Percentage of Patients Alive and Free of Respiratory Failure at Day 28 | 15.4 percentage of participants |
Secondary
Percentage of Patients Alive and Out of Intensive Care Unit (ICU) at Day 28
The percentage of patients alive and out of ICU at Day 28 is presented by treatment group.
Time frame: Day 28
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Cohort | Percentage of Patients Alive and Out of Intensive Care Unit (ICU) at Day 28 | 37.5 percentage of participants |
| Poractant Alfa Treated Cohort | Percentage of Patients Alive and Out of Intensive Care Unit (ICU) at Day 28 | 7.7 percentage of participants |
Secondary
Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint
The percentages of patients in categories of PaO2/FiO2 ratio improvement compared to baseline (\>20%) at all timepoints post-baseline are summarised by treatment group.
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Control Cohort | Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint | 6 hours | 37.5 percentage of participants |
| Control Cohort | Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint | 12 hours | 62.5 percentage of participants |
| Control Cohort | Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint | 24 hours | 50.0 percentage of participants |
| Control Cohort | Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint | 30 hours | 57.1 percentage of participants |
| Control Cohort | Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint | 36 hours | 50.0 percentage of participants |
| Control Cohort | Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint | 48 hours | 50.0 percentage of participants |
| Control Cohort | Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint | 54 hours | 71.4 percentage of participants |
| Control Cohort | Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint | 60 hours | 28.6 percentage of participants |
| Control Cohort | Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint | 72 hours | 14.3 percentage of participants |
| Control Cohort | Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint | 28 day | 25.0 percentage of participants |
| Poractant Alfa Treated Cohort | Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint | 60 hours | 38.5 percentage of participants |
| Poractant Alfa Treated Cohort | Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint | 6 hours | 46.2 percentage of participants |
| Poractant Alfa Treated Cohort | Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint | 48 hours | 46.2 percentage of participants |
| Poractant Alfa Treated Cohort | Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint | 12 hours | 41.7 percentage of participants |
| Poractant Alfa Treated Cohort | Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint | 28 day | 27.3 percentage of participants |
| Poractant Alfa Treated Cohort | Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint | 24 hours | 38.5 percentage of participants |
| Poractant Alfa Treated Cohort | Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint | 54 hours | 58.3 percentage of participants |
| Poractant Alfa Treated Cohort | Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint | 30 hours | 38.5 percentage of participants |
| Poractant Alfa Treated Cohort | Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint | 72 hours | 33.3 percentage of participants |
| Poractant Alfa Treated Cohort | Percentage of Patients Alive and With PaO2/FiO2 Ratio Improvement >20% Compared to Baseline at Each Timepoint | 36 hours | 53.8 percentage of participants |
Secondary
Percentage of Patients With Improvement in Severity Status at Day 28 or Discharge (Severity Score: Mild, Moderate, Severe, or Death)
The severity status of patients at baseline and at Day 28/Discharge and the percentage of patients with improvement in severity status (i.e. a decrease of at least 1 point in severity status) at Day 28/Discharge relative to baseline is presented. Severity was assessed using a point score system: Severity score was defined as mild, moderate, severe (see below\*), or death and was based on PaO2/FiO2 ratio and patient status at Day 28/Discharge and numerically rated from 1-4, respectively. An improvement in severity was defined as a decrease of at least 1 point between baseline and Day 28/Discharge. At Day 28 the last follow up evaluation took place on the ICU if, still requiring critical care, or by phone call if the patient has been discharged from ICU by that time. \*Mild: 200 mmHg \< PaO2/FiO2 ratio ≤300 mmHg; Moderate: 100 mmHg \< PaO2/FiO2 ratio ≤200 mmHg; Severe: PaO2/FiO2 ratio ≤100 mmHg
Time frame: Day 28 or Discharge, whichever comes first
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Control Cohort | Percentage of Patients With Improvement in Severity Status at Day 28 or Discharge (Severity Score: Mild, Moderate, Severe, or Death) | 50.0 percentage of participants |
| Poractant Alfa Treated Cohort | Percentage of Patients With Improvement in Severity Status at Day 28 or Discharge (Severity Score: Mild, Moderate, Severe, or Death) | 25.0 percentage of participants |
Secondary
Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28
Ventilatory parameter: Change from baseline in dynamic compliance (mL/cmH2O) at all timepoints up to Day 3 (72 hours) and at Day 28. The change was calculated from two time points as the value at the later time point minus the value at baseline. Dynamic compliance: is the continuous measurement of pulmonary compliance calculated at each point representing schematic changes during rhythmic breathing. Dynamic compliance monitors both elastic and airway resistance.
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.~At each time point the number of patients that contributed with a result value is indicated for both study arms.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control Cohort | Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 28 day | -5.25 mL/cmH2O |
| Control Cohort | Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 6 hours | -1.0 mL/cmH2O |
| Control Cohort | Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 12 hours | 0.50 mL/cmH2O |
| Control Cohort | Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 24 hours | 1.20 mL/cmH2O |
| Control Cohort | Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 30 hours | 7.50 mL/cmH2O |
| Control Cohort | Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 36 hours | 3.00 mL/cmH2O |
| Control Cohort | Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 48 hours | 2.00 mL/cmH2O |
| Control Cohort | Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 54 hours | 1.80 mL/cmH2O |
| Control Cohort | Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 60 hours | 0.85 mL/cmH2O |
| Control Cohort | Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 72 hours | -1.25 mL/cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 54 hours | 0.98 mL/cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 28 day | -3.10 mL/cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 36 hours | 2.25 mL/cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 6 hours | 0.70 mL/cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 72 hours | 0.0 mL/cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 12 hours | -0.70 mL/cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 48 hours | 0.52 mL/cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 24 hours | -0.55 mL/cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 60 hours | -0.05 mL/cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Dynamic Compliance -- Change From Baseline in Dynamic Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 30 hours | 1.30 mL/cmH2O |
Secondary
Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28
Ventilatory parameter: Peak Inspiratory Pressure -- Change from baseline in peak inspiratory pressure (cmH2O) at all timepoints up to Day 3 (72 hours) and at Day 28. The change was calculated from two time points as the value at the later time point minus the value at baseline. At each time point the number of patients that contributed with a result value is indicated for both study arms. Peak inspiratory pressure (PIP) is the highest level of pressure applied to the lungs during inhalation. In mechanical ventilation the number reflects a positive pressure in centimetres of water pressure (cmH2O).
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control Cohort | Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 12 hours | 2.00 cmH2O |
| Control Cohort | Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 24 hours | 3.00 cmH2O |
| Control Cohort | Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 30 hours | 1.00 cmH2O |
| Control Cohort | Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 48 hours | 0.00 cmH2O |
| Control Cohort | Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 54 hours | 2.00 cmH2O |
| Control Cohort | Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 6 hours | 0.00 cmH2O |
| Control Cohort | Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 36 hours | 3.00 cmH2O |
| Control Cohort | Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 60 hours | 0.00 cmH2O |
| Control Cohort | Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 72 hours | 4.50 cmH2O |
| Control Cohort | Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 28 day | 4.00 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 12 hours | 0.00 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 54 hours | -3.00 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 24 hours | -0.50 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 28 day | -4.00 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 30 hours | -2.00 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 36 hours | -1.00 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 60 hours | -3.00 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 48 hours | -2.00 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 6 hours | 0.00 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Peak Inspiratory Pressure -- Change From Baseline in Peak Inspiratory Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 72 hours | -3.00 cmH2O |
Secondary
Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28
Ventilatory parameter: Plateau Pressure -- Change from baseline in plateau pressure (cmH2O) at all timepoints up to Day 3 (72 hours) and at Day 28. The change was calculated from two time points as the value at the later time point minus the value at baseline. At each time point the number of patients that contributed with a result value is indicated for both study arms. Plateau pressure is the pressure that is applied by the mechanical ventilator to the small airways and alveoli.
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation, and Day 28
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control Cohort | Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 6 hours | 1.25 cmH2O |
| Control Cohort | Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 12 hours | 2.00 cmH2O |
| Control Cohort | Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 24 hours | 0.50 cmH2O |
| Control Cohort | Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 30 hours | 0.00 cmH2O |
| Control Cohort | Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 36 hours | 1.00 cmH2O |
| Control Cohort | Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 28 day | 2.00 cmH2O |
| Control Cohort | Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 48 hours | 3.00 cmH2O |
| Control Cohort | Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 54 hours | 1.50 cmH2O |
| Control Cohort | Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 60 hours | 0.50 cmH2O |
| Control Cohort | Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 72 hours | 1.50 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 54 hours | -3.50 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 6 hours | -1.00 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 28 day | -4.00 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 12 hours | -1.50 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 30 hours | -3.00 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 24 hours | -1.50 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 48 hours | -3.00 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 60 hours | -2.50 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 36 hours | -2.00 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Plateau Pressure -- Change From Baseline in Plateau Pressure (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 72 hours | -3.00 cmH2O |
Secondary
Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28
Ventilatory parameter: Positive End-Expiratory Pressure -- Change from baseline in PEEP (cmH2O) at all timepoints up to Day 3 (72 hours) and at Day 28. The change was calculated from two time points as the value at the later time point minus the value at baseline. At each time point the number of patients that contributed with a result value is indicated for both study arms. Positive end-expiratory pressure (PEEP) is the positive pressure that will remain in the airways at the end of the respiratory cycle (end of exhalation) that is greater than the atmospheric pressure in mechanically ventilated patients.
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control Cohort | Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 30 hours | 0.00 cmH2O |
| Control Cohort | Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 6 hours | 0.00 cmH2O |
| Control Cohort | Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 54 hours | -0.50 cmH2O |
| Control Cohort | Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 12 hours | 0.50 cmH2O |
| Control Cohort | Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 60 hours | -0.45 cmH2O |
| Control Cohort | Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 48 hours | 0.00 cmH2O |
| Control Cohort | Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 72 hours | -1.00 cmH2O |
| Control Cohort | Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 28 day | -3.20 cmH2O |
| Control Cohort | Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 24 hours | 2.00 cmH2O |
| Control Cohort | Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 36 hours | 0.00 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 24 hours | 0.00 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 72 hours | 0.00 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 12 hours | 0.00 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 36 hours | 0.00 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 6 hours | 0.00 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 48 hours | 0.00 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 54 hours | -0.50 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 60 hours | -0.50 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 28 day | -2.00 cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Positive End-Expiratory Pressure (PEEP) -- Change From Baseline in PEEP (cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 30 hours | 0.00 cmH2O |
Secondary
Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28
Ventilatory parameter: Change from baseline in respiratory rate (breaths/minute) at all timepoints up to Day 3 (72 hours) and at Day 28. The change was calculated from two time points as the value at the later time point minus the value at baseline. Respiratory rate is the number of breaths taken per minute.
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control Cohort | Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 54 hours | 0.00 breaths/minute |
| Control Cohort | Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 60 hours | 0.0 breaths/minute |
| Control Cohort | Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 72 hours | 1.0 breaths/minute |
| Control Cohort | Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 28 day | 10.0 breaths/minute |
| Control Cohort | Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 6 hours | 0.0 breaths/minute |
| Control Cohort | Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 12 hours | 0.0 breaths/minute |
| Control Cohort | Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 24 hours | 2.50 breaths/minute |
| Control Cohort | Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 30 hours | 4.0 breaths/minute |
| Control Cohort | Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 36 hours | 1.0 breaths/minute |
| Control Cohort | Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 48 hours | 1.50 breaths/minute |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 48 hours | 0.0 breaths/minute |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 12 hours | 0.0 breaths/minute |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 36 hours | 0.0 breaths/minute |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 28 day | 14.0 breaths/minute |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 54 hours | 0.0 breaths/minute |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 60 hours | 0.0 breaths/minute |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 72 hours | 0.00 breaths/minute |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 24 hours | 0.0 breaths/minute |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 30 hours | 0.0 breaths/minute |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Respiratory Rate -- Change From Baseline in Respiratory Rate (Breaths/Minute) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 6 hours | 0.0 breaths/minute |
Secondary
Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28
Ventilatory parameter: static compliance -- change from baseline in static compliance (mL/cmH2O) at all timepoints up to Day 3 (72 hours) and at Day 28. The change was calculated from two time points as the value at the later time point minus the value at baseline. At each time point the number of patients that contributed with a result value is indicated for both study arms. Static Compliance: represents pulmonary compliance at a given fixed volume when there is no airflow, and muscles are relaxed.
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control Cohort | Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 6 hours | -2.00 mL/cmH2O |
| Control Cohort | Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 12 hours | 0.15 mL/cmH2O |
| Control Cohort | Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 24 hours | 1.54 mL/cmH2O |
| Control Cohort | Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 30 hours | 7.00 mL/cmH2O |
| Control Cohort | Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 36 hours | 2.50 mL/cmH2O |
| Control Cohort | Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 54 hours | 1.80 mL/cmH2O |
| Control Cohort | Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 60 hours | 0.85 mL/cmH2O |
| Control Cohort | Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 48 hours | -3.50 mL/cmH2O |
| Control Cohort | Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 72 hours | 3.00 mL/cmH2O |
| Control Cohort | Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 28 day | -24.50 mL/cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 60 hours | -0.40 mL/cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 6 hours | 0.40 mL/cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 28 day | -2.70 mL/cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 12 hours | -0.81 mL/cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 24 hours | -0.40 mL/cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 48 hours | -0.40 mL/cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 30 hours | 1.30 mL/cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 54 hours | -0.26 mL/cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 36 hours | 2.10 mL/cmH2O |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Static Compliance -- Change From Baseline in Static Compliance (mL/cmH2O) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 72 hours | 0.30 mL/cmH2O |
Secondary
Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28
Ventilatory parameter: Change from baseline in tidal volume (mL/kg BW) at all timepoints up to Day 3 (72 hours) and at Day 28. The change was calculated from two time points as the value at the later time point minus the value at baseline. Tidal volume is the amount of air that moves in or out of the lungs with each respiratory cycle.
Time frame: up to 28 days: 6, 12, 24, 30, 36, 48, 54, 60, 72 hours after randomisation and Day 28
Population: Intention-to-Treat (ITT) population: all randomised patients who had at least one available evaluation of efficacy after baseline.~Data was summarised by treatment group using, descriptive statistics. Due to low recruitment rate the study was terminated early for non-safety reasons.
| Arm | Measure | Group | Value (MEDIAN) |
|---|---|---|---|
| Control Cohort | Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 6 hours | 1.50 mL/kg BW |
| Control Cohort | Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 12 hours | 4.50 mL/kg BW |
| Control Cohort | Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 24 hours | 15.00 mL/kg BW |
| Control Cohort | Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 30 hours | 61.00 mL/kg BW |
| Control Cohort | Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 36 hours | 54.50 mL/kg BW |
| Control Cohort | Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 48 hours | -34.00 mL/kg BW |
| Control Cohort | Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 54 hours | 7.00 mL/kg BW |
| Control Cohort | Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 60 hours | -8.00 mL/kg BW |
| Control Cohort | Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 72 hours | 73.50 mL/kg BW |
| Control Cohort | Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 28 day | 5.00 mL/kg BW |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 60 hours | 17.00 mL/kg BW |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 6 hours | -1.00 mL/kg BW |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 48 hours | -17.00 mL/kg BW |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 12 hours | 13.00 mL/kg BW |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 28 day | -90.50 mL/kg BW |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 24 hours | 0.00 mL/kg BW |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 54 hours | 30.00 mL/kg BW |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 30 hours | -18.00 mL/kg BW |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 72 hours | 11.50 mL/kg BW |
| Poractant Alfa Treated Cohort | Ventilatory Parameter: Tidal Volume -- Change From Baseline in Tidal Volume (mL/kg BW) at All Timepoints up to Day 3 (72 Hours) and at Day 28 | 36 hours | 13.40 mL/kg BW |