Cytokine Storm (Covid-19)
Conditions
Keywords
COVID-19 pneumonia, cytokine release syndrome, SARS-COV-2, ruxolitinib
Brief summary
This was a randomized, double-blind, placebo-controlled, 29-day, multicenter study to assess the efficacy and safety of ruxolitinib + standard-of-care (SoC) therapy, compared with placebo + SoC therapy, in patients aged ≥12 years with COVID-19 disease.
Detailed description
This was a Phase III, multicenter, double-blind, randomized, placebo-controlled study to assess the efficacy and safety of ruxolitinib in patients aged ≥12 years with COVID-19 disease. The study enrolled patients to ruxolitinib or placebo, in addition to standard of care (SoC) per local practice. Patients who meet the inclusion/exclusion criteria were randomized in a 2:1 ratio to either oral ruxolitinib 5 mg twice daily + SoC or oral matching-image placebo + SoC for a total of 14 days. An additional 14 days of study drug could be given if in the opinion of the investigator the patient's clinical signs and symptoms did not improve, or worsen, and the potential benefit outweighed the potential risk. The study included: * Screening period of 0-2 days. * Study period of 29 days (treatment of 14 days with possible extension of treatment to 28 days). The primary objective was to evaluate the efficacy (as measured by a composite endpoint of proportion of patients who die, develop respiratory failure \[require mechanical ventilation\], or require intensive care unit care) of ruxolitinib + standard-of-care (SoC) therapy compared with placebo + SoC therapy, for the treatment of COVID-19 by Day 29.
Interventions
DRUGRuxolitinib
Ruxolitinib 5 mg tablets
DRUGPlacebo
Matching-image placebo
Sponsors
Incyte Corporation
Novartis Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
12 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Patient or guardian/health proxy must provide informed consent (and assent if applicable) before any study assessment is performed. Male and female patients aged ≥ 12 years (or ≥ the lower age limit allowed by Health Authority and/or Ethics Committee/Institutional Review Board approvals). Patients with coronavirus (SARS-CoV-2) infection confirmed by polymerase chain reaction (PCR) test or another rapid test from the respiratory tract prior to randomization. Patients currently hospitalized or will be hospitalized prior to randomization. Patients, who meet at least one of the below criteria: * Pulmonary infiltrates (chest X ray or chest CT scan); * Respiratory frequency ≥ 30/min; * Requiring supplemental oxygen; * Oxygen saturation ≤ 94% on room air; * Arterial oxygen partial pressure (PaO2)/ fraction of inspired oxygen (FiO2) \< 300mmHg (1mmHg=0.133kPa) (corrective formulation should be used for higher altitude regions (over 1000m).
Exclusion criteria
History of hypersensitivity to any drugs or metabolites of similar chemical classes as ruxolitinib. Presence of severely impaired renal function defined by serum creatinine \> 2 mg/dL (\>176.8 μmol/L), or have estimated creatinine clearance \< 30 ml/min measured or calculated by Cockroft Gault equation or calculated by the updated bedside Schwartz equation. Suspected uncontrolled bacterial, fungal, viral, or other infection (besides COVID-19). Currently intubated or intubated between screening and randomization. In intensive care unit (ICU) at time of randomization. Intubated or in ICU for COVID-19 disease prior to screening. Patients who are on anti-rejection, immunosuppressant or immunomodulatory drugs (i.e. tocilizumab, ruxolitinib, canakinumab, sarilumab, anakinra). Unable to ingest tablets at randomization. Pregnant or nursing (lactating) women
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Proportion of Patients Who Die, Develop Respiratory Failure [Require Mechanical Ventilation] or Require Intensive Care Unit (ICU) Care | Day 1 - Day 29 | Efficacy is measured by a composite endpoint of proportion of patients who die, develop respiratory failure \[require mechanical ventilation\], or require intensive care unit \[ICU\] care for the treatment of COVID-19. Analyses are cumulative, thus analysis on Day 29 includes all events till that day. Patients who developed respiratory failure and/or required ICU at randomization are excluded from the analysis. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Patients With at Least Two-point Improvement From Baseline in Clinical Status | Baseline, Day 15, Day 29 | Percentage of patients with at least two points improvement in clinical status on the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are treated as non-responders. |
| Percentage of Patients With at Least One-point Improvement From Baseline in Clinical Status | Baseline, Day 15, Day 29 | Percentage of patients with at least one point improvement in clinical status on the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are treated as non-responders. |
| Percentage of Patients With at Least One-point Deterioration From Baseline in Clinical Status | Baseline, Day 15, Day 29 | Percentage of patients with at least one point deterioration in clinical status on the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are treated as non-responders. |
| Time to Improvement in Clinical Status | 29 days | Time to improvement in clinical status from baseline category to one less severe category of the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Median time to improvement is estimated by Kaplan-Meier method, with dead patients being censored at the maximum follow-up time in the study. Patients who did not achieve improvement and did not die are censored at their last clinical status assessment date. |
| Mean Change From Baseline in the Clinical Status | Baseline, Day 15, Day 29 | Mean change from baseline in the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are excluded from the analysis. A negative change from baseline in the clinical status is a favorable outcome. |
| Mortality Rate | Day 15, Day 29 | Mortality rate is determined as the proportion of participants who died by study Day 15 and Day 29 |
| Clinical Status | Baseline, Day 15, Day 29 | Clinical status is measured with the 9-point ordinal scale. The scoring is: * Uninfected patients have a score 0 (no clinical or virological evidence of infection). * Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). * Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as peripheral oxygen saturation (SpO2) ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). * Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). * Patients who die have a score 8. |
| Duration of Hospitalization | 29 days | Duration of hospitalization is defined as time to hospital discharge. Median time to hospital discharge is estimated by Kaplan-Meier method, with dead patients being censored at the maximum follow-up time in the study. Patients who were not discharged and did not die are censored at their last assessment date. |
| Time to Hospital Discharge or to a NEWS2 Score of ≤2 | 29 days | The time to hospital discharge or to a National Early Warning Score 2 (NEWS2) of ≤2 and maintained for 24 hours whichever comes first. The NEWS2 is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst). Median time is estimated by Kaplan-Meier method, with dead patients being censored at the maximum follow-up time in the study. |
| Change From Baseline in NEWS2 Score | Baseline, Days 3, 5, 8, 11, 15, and 29 | The National Early Warning Score 2 (NEWS2) is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst). At each visit, only patients with a value at both baseline and the respective visit are included. A negative change from baseline in NEWS2 score is a favorable outcome. |
| Change From Baseline in SpO2/FiO2 Ratio | Baseline, Day 15, Day 29 | Change from baseline in peripheral oxygen saturation / fraction of inspired oxygen ratio (SpO2/FiO2 ratio). At each visit, only patients with a value at both baseline and the respective visit are included. A positive change from baseline in SpO2/FiO2 ratio is a favorable outcome. |
| Proportion of Patients With no Oxygen Therapy | Day 15, Day 29 | Proportion of patients with no oxygen therapy (defined as oxygen saturation ≥ 94% on room air) at Days 15 and 29. Analyses are cumulative, thus analysis on each day includes all events till that day. Patients with missing data at Day 15 and/or Day 29 are excluded from the analysis. |
| Proportion of Patients Requiring Mechanical Ventilation | Day 1 - Day 29 | Proportion of patients requiring mechanical ventilation. Analyses are cumulative, thus analysis on Day 29 includes all events till that day. Patients who required mechanical ventilation at randomization are excluded from the analysis. |
Countries
Argentina, Brazil, Colombia, France, Germany, Mexico, Peru, Russia, Spain, Turkey (Türkiye), United Kingdom, United States
Participant flow
Recruitment details
Participants took part in 61 investigative sites in 12 countries.
Pre-assignment details
Patients were to be randomized on the same day as screening or up to 2 days after completing the screening procedures.
Participants by arm
| Arm | Count |
|---|---|
| Ruxolitinib 5 mg Ruxolitinib 5 mg tablets twice daily (b.i.d.) for 14 days with possible extension of treatment to 28 days | 287 |
| Placebo Matching-image placebo for 14 days with possible extension of treatment to 28 days | 145 |
| Total | 432 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 |
| Overall Study | Death | 9 | 3 |
| Overall Study | Lost to Follow-up | 1 | 0 |
| Overall Study | Patient decision | 6 | 3 |
| Overall Study | Protocol deviation | 1 | 0 |
Baseline characteristics
| Characteristic | Ruxolitinib 5 mg | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 56.4 years STANDARD_DEVIATION 13.7 | 56.9 years STANDARD_DEVIATION 12.5 | 56.5 years STANDARD_DEVIATION 13.3 |
| Race/Ethnicity, Customized American Indian Or Alaska Native | 26 Participants | 13 Participants | 39 Participants |
| Race/Ethnicity, Customized Asian | 5 Participants | 5 Participants | 10 Participants |
| Race/Ethnicity, Customized Black Or African American | 6 Participants | 9 Participants | 15 Participants |
| Race/Ethnicity, Customized Multiple | 3 Participants | 2 Participants | 5 Participants |
| Race/Ethnicity, Customized Unknown | 5 Participants | 7 Participants | 12 Participants |
| Race/Ethnicity, Customized White | 242 Participants | 109 Participants | 351 Participants |
| Sex: Female, Male Female | 125 Participants | 72 Participants | 197 Participants |
| Sex: Female, Male Male | 162 Participants | 73 Participants | 235 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 9 / 281 | 3 / 143 |
| other Total, other adverse events | 113 / 281 | 62 / 143 |
| serious Total, serious adverse events | 31 / 281 | 15 / 143 |
Outcome results
Primary
Proportion of Patients Who Die, Develop Respiratory Failure [Require Mechanical Ventilation] or Require Intensive Care Unit (ICU) Care
Efficacy is measured by a composite endpoint of proportion of patients who die, develop respiratory failure \[require mechanical ventilation\], or require intensive care unit \[ICU\] care for the treatment of COVID-19. Analyses are cumulative, thus analysis on Day 29 includes all events till that day. Patients who developed respiratory failure and/or required ICU at randomization are excluded from the analysis.
Time frame: Day 1 - Day 29
Population: Randomized participants excluding those who developed respiratory failure and/or required ICU at randomization.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ruxolitinib 5 mg | Proportion of Patients Who Die, Develop Respiratory Failure [Require Mechanical Ventilation] or Require Intensive Care Unit (ICU) Care | 34 Participants |
| Placebo | Proportion of Patients Who Die, Develop Respiratory Failure [Require Mechanical Ventilation] or Require Intensive Care Unit (ICU) Care | 17 Participants |
p-value: 0.76995% CI: [0.48, 1.73]Regression, Logistic
Secondary
Change From Baseline in NEWS2 Score
The National Early Warning Score 2 (NEWS2) is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst). At each visit, only patients with a value at both baseline and the respective visit are included. A negative change from baseline in NEWS2 score is a favorable outcome.
Time frame: Baseline, Days 3, 5, 8, 11, 15, and 29
Population: Randomized participants with a valid assessment for the outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ruxolitinib 5 mg | Change From Baseline in NEWS2 Score | Day 29 | -2.3 score on scale | Standard Deviation 2.37 |
| Ruxolitinib 5 mg | Change From Baseline in NEWS2 Score | Day 15 | -1.9 score on scale | Standard Deviation 2.34 |
| Ruxolitinib 5 mg | Change From Baseline in NEWS2 Score | Day 3 | -0.7 score on scale | Standard Deviation 1.91 |
| Ruxolitinib 5 mg | Change From Baseline in NEWS2 Score | Day 5 | -1.0 score on scale | Standard Deviation 2.02 |
| Ruxolitinib 5 mg | Change From Baseline in NEWS2 Score | Day 8 | -1.3 score on scale | Standard Deviation 2.25 |
| Ruxolitinib 5 mg | Change From Baseline in NEWS2 Score | Day 11 | -1.1 score on scale | Standard Deviation 2.7 |
| Placebo | Change From Baseline in NEWS2 Score | Day 15 | -2.2 score on scale | Standard Deviation 2.35 |
| Placebo | Change From Baseline in NEWS2 Score | Day 8 | -1.3 score on scale | Standard Deviation 2.6 |
| Placebo | Change From Baseline in NEWS2 Score | Day 29 | -2.5 score on scale | Standard Deviation 2.17 |
| Placebo | Change From Baseline in NEWS2 Score | Day 3 | -0.6 score on scale | Standard Deviation 2.13 |
| Placebo | Change From Baseline in NEWS2 Score | Day 11 | -1.3 score on scale | Standard Deviation 2.74 |
| Placebo | Change From Baseline in NEWS2 Score | Day 5 | -0.8 score on scale | Standard Deviation 2.19 |
Secondary
Change From Baseline in SpO2/FiO2 Ratio
Change from baseline in peripheral oxygen saturation / fraction of inspired oxygen ratio (SpO2/FiO2 ratio). At each visit, only patients with a value at both baseline and the respective visit are included. A positive change from baseline in SpO2/FiO2 ratio is a favorable outcome.
Time frame: Baseline, Day 15, Day 29
Population: Randomized participants with a valid assessment of the outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ruxolitinib 5 mg | Change From Baseline in SpO2/FiO2 Ratio | Day 15 | 90.110 no units | Standard Deviation 104.4783 |
| Ruxolitinib 5 mg | Change From Baseline in SpO2/FiO2 Ratio | Day 29 | 105.553 no units | Standard Deviation 98.2452 |
| Placebo | Change From Baseline in SpO2/FiO2 Ratio | Day 15 | 106.766 no units | Standard Deviation 100.9778 |
| Placebo | Change From Baseline in SpO2/FiO2 Ratio | Day 29 | 109.710 no units | Standard Deviation 95.4279 |
Secondary
Clinical Status
Clinical status is measured with the 9-point ordinal scale. The scoring is: * Uninfected patients have a score 0 (no clinical or virological evidence of infection). * Ambulatory patients (not in hospital or in hospital and ready for discharge) can have a score 1 (no limitation of activities) or 2 (limitation of activities). * Hospitalized patients with mild disease can have score 3 (no oxygen therapy defined as peripheral oxygen saturation (SpO2) ≥ 94% on room air) or 4 (oxygen by mask or nasal prongs). * Hospitalized patients with severe disease can have score 5 (non-invasive ventilation or high-flow oxygen), 6 (intubation and mechanical ventilation) or 7 (ventilation + additional organ support - pressors, RRT (renal replacement therapy), ECMO (extracorporeal membrane oxygenation)). * Patients who die have a score 8.
Time frame: Baseline, Day 15, Day 29
Population: Randomized participants with a valid assessment for the outcome measure.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Ruxolitinib 5 mg | Clinical Status | Baseline | 3.7 score on scale | Standard Deviation 0.56 |
| Ruxolitinib 5 mg | Clinical Status | Day 15 | 1.8 score on scale | Standard Deviation 1.54 |
| Ruxolitinib 5 mg | Clinical Status | Day 29 | 1.1 score on scale | Standard Deviation 1.61 |
| Placebo | Clinical Status | Baseline | 3.7 score on scale | Standard Deviation 0.53 |
| Placebo | Clinical Status | Day 15 | 1.8 score on scale | Standard Deviation 1.41 |
| Placebo | Clinical Status | Day 29 | 1.0 score on scale | Standard Deviation 1.41 |
Secondary
Duration of Hospitalization
Duration of hospitalization is defined as time to hospital discharge. Median time to hospital discharge is estimated by Kaplan-Meier method, with dead patients being censored at the maximum follow-up time in the study. Patients who were not discharged and did not die are censored at their last assessment date.
Time frame: 29 days
Population: Randomized participants with a valid assessment for the outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ruxolitinib 5 mg | Duration of Hospitalization | 9.0 days |
| Placebo | Duration of Hospitalization | 9.0 days |
p-value: 0.73895% CI: [0.84, 1.28]Proportional hazards model
Secondary
Mean Change From Baseline in the Clinical Status
Mean change from baseline in the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are excluded from the analysis. A negative change from baseline in the clinical status is a favorable outcome.
Time frame: Baseline, Day 15, Day 29
Population: Randomized participants with a valid assessment for the outcome measure.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Ruxolitinib 5 mg | Mean Change From Baseline in the Clinical Status | Day 15 | -1.96 score on scale | Standard Error 0.084 |
| Ruxolitinib 5 mg | Mean Change From Baseline in the Clinical Status | Day 29 | -2.61 score on scale | Standard Error 0.09 |
| Placebo | Mean Change From Baseline in the Clinical Status | Day 15 | -1.93 score on scale | Standard Error 0.118 |
| Placebo | Mean Change From Baseline in the Clinical Status | Day 29 | -2.69 score on scale | Standard Error 0.126 |
Comparison: Day 15p-value: 0.83195% CI: [-0.31, 0.25]ANCOVA
Comparison: Day 29p-value: 0.62495% CI: [-0.23, 0.38]ANCOVA
Secondary
Mortality Rate
Mortality rate is determined as the proportion of participants who died by study Day 15 and Day 29
Time frame: Day 15, Day 29
Population: All randomized participants including those who did not receive any dose, as per intent-to-treat principle, and excluding patients lost to follow up.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ruxolitinib 5 mg | Mortality Rate | Day 29 | 9 Participants |
| Ruxolitinib 5 mg | Mortality Rate | Day 15 | 6 Participants |
| Placebo | Mortality Rate | Day 15 | 2 Participants |
| Placebo | Mortality Rate | Day 29 | 3 Participants |
Comparison: Day 15p-value: 0.94495% CI: [0.2, 5.57]Regression, Logistic
Comparison: Day 29p-value: 0.77595% CI: [0.35, 5.11]Regression, Logistic
Secondary
Percentage of Patients With at Least One-point Deterioration From Baseline in Clinical Status
Percentage of patients with at least one point deterioration in clinical status on the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are treated as non-responders.
Time frame: Baseline, Day 15, Day 29
Population: Randomized participants with a valid assessment of clinical status at baseline.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ruxolitinib 5 mg | Percentage of Patients With at Least One-point Deterioration From Baseline in Clinical Status | Day 15 | 16 Participants |
| Ruxolitinib 5 mg | Percentage of Patients With at Least One-point Deterioration From Baseline in Clinical Status | Day 29 | 14 Participants |
| Placebo | Percentage of Patients With at Least One-point Deterioration From Baseline in Clinical Status | Day 15 | 9 Participants |
| Placebo | Percentage of Patients With at Least One-point Deterioration From Baseline in Clinical Status | Day 29 | 5 Participants |
Comparison: Day 15p-value: 0.53295% CI: [0.31, 1.83]Regression, Logistic
Comparison: Day 29p-value: 0.76495% CI: [0.4, 3.49]Regression, Logistic
Secondary
Percentage of Patients With at Least One-point Improvement From Baseline in Clinical Status
Percentage of patients with at least one point improvement in clinical status on the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are treated as non-responders.
Time frame: Baseline, Day 15, Day 29
Population: Randomized participants with a valid assessment of clinical status at baseline.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ruxolitinib 5 mg | Percentage of Patients With at Least One-point Improvement From Baseline in Clinical Status | Day 15 | 250 Participants |
| Ruxolitinib 5 mg | Percentage of Patients With at Least One-point Improvement From Baseline in Clinical Status | Day 29 | 261 Participants |
| Placebo | Percentage of Patients With at Least One-point Improvement From Baseline in Clinical Status | Day 15 | 128 Participants |
| Placebo | Percentage of Patients With at Least One-point Improvement From Baseline in Clinical Status | Day 29 | 136 Participants |
Comparison: Day 15p-value: 0.94695% CI: [0.51, 1.87]Regression, Logistic
Comparison: Day 29p-value: 0.57395% CI: [0.35, 1.79]Regression, Logistic
Secondary
Percentage of Patients With at Least Two-point Improvement From Baseline in Clinical Status
Percentage of patients with at least two points improvement in clinical status on the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Patients with missing data at Day 15 and/or Day 29 are treated as non-responders.
Time frame: Baseline, Day 15, Day 29
Population: Randomized participants with a valid assessment of clinical status at baseline.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ruxolitinib 5 mg | Percentage of Patients With at Least Two-point Improvement From Baseline in Clinical Status | Day 15 | 206 Participants |
| Ruxolitinib 5 mg | Percentage of Patients With at Least Two-point Improvement From Baseline in Clinical Status | Day 29 | 252 Participants |
| Placebo | Percentage of Patients With at Least Two-point Improvement From Baseline in Clinical Status | Day 15 | 108 Participants |
| Placebo | Percentage of Patients With at Least Two-point Improvement From Baseline in Clinical Status | Day 29 | 129 Participants |
Comparison: Day 15p-value: 0.64795% CI: [0.55, 1.46]Regression, Logistic
Comparison: Day 29p-value: 0.99795% CI: [0.52, 1.92]Regression, Logistic
Secondary
Proportion of Patients Requiring Mechanical Ventilation
Proportion of patients requiring mechanical ventilation. Analyses are cumulative, thus analysis on Day 29 includes all events till that day. Patients who required mechanical ventilation at randomization are excluded from the analysis.
Time frame: Day 1 - Day 29
Population: Randomized participants with a valid assessment for the outcome measure.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Ruxolitinib 5 mg | Proportion of Patients Requiring Mechanical Ventilation | 22 Participants |
| Placebo | Proportion of Patients Requiring Mechanical Ventilation | 10 Participants |
p-value: 0.98795% CI: [0.45, 2.21]Regression, Logistic
Secondary
Proportion of Patients With no Oxygen Therapy
Proportion of patients with no oxygen therapy (defined as oxygen saturation ≥ 94% on room air) at Days 15 and 29. Analyses are cumulative, thus analysis on each day includes all events till that day. Patients with missing data at Day 15 and/or Day 29 are excluded from the analysis.
Time frame: Day 15, Day 29
Population: Randomized participants with a valid assessment of the outcome measure.
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Ruxolitinib 5 mg | Proportion of Patients With no Oxygen Therapy | Day 15 | 255 Participants |
| Ruxolitinib 5 mg | Proportion of Patients With no Oxygen Therapy | Day 29 | 262 Participants |
| Placebo | Proportion of Patients With no Oxygen Therapy | Day 15 | 133 Participants |
| Placebo | Proportion of Patients With no Oxygen Therapy | Day 29 | 136 Participants |
Comparison: Day 15p-value: 0.32595% CI: [0.23, 1.63]Regression, Logistic
Comparison: Day 2995% CI: [0.25, 5.4]Regression, Logistic
Secondary
Time to Hospital Discharge or to a NEWS2 Score of ≤2
The time to hospital discharge or to a National Early Warning Score 2 (NEWS2) of ≤2 and maintained for 24 hours whichever comes first. The NEWS2 is based on a simple aggregate scoring system in which a score is allocated to physiological measurements, already recorded in routine practice presentation or when a patient is being monitored in hospital. The score ranges from 0 (best) to 23 (worst). Median time is estimated by Kaplan-Meier method, with dead patients being censored at the maximum follow-up time in the study.
Time frame: 29 days
Population: Randomized participants with a valid assessment for the outcome measure.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ruxolitinib 5 mg | Time to Hospital Discharge or to a NEWS2 Score of ≤2 | 4.0 days |
| Placebo | Time to Hospital Discharge or to a NEWS2 Score of ≤2 | 4.0 days |
p-value: 0.86995% CI: [0.84, 1.23]Proportional hazards model
Secondary
Time to Improvement in Clinical Status
Time to improvement in clinical status from baseline category to one less severe category of the 9-point ordinal scale. The baseline value of clinical status is defined as the last assessment prior to first dose of double-blind treatment. Median time to improvement is estimated by Kaplan-Meier method, with dead patients being censored at the maximum follow-up time in the study. Patients who did not achieve improvement and did not die are censored at their last clinical status assessment date.
Time frame: 29 days
Population: Randomized participants with a valid assessment of clinical status at baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Ruxolitinib 5 mg | Time to Improvement in Clinical Status | 9.0 days |
| Placebo | Time to Improvement in Clinical Status | 9.0 days |
p-value: 0.3395% CI: [0.9, 1.37]Proportional hazards model
Post Hoc
All Collected Deaths
Deaths in the safety population were evaluated in all participants who received at least one dose of double-blind treatment. Total deaths were evaluated in all participants randomized.
Time frame: 29 days
Population: Clinical database population - all randomized participants
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Ruxolitinib 5 mg | All Collected Deaths | Deaths in the safety population | 9 participants |
| Ruxolitinib 5 mg | All Collected Deaths | Total deaths | 9 participants |
| Placebo | All Collected Deaths | Deaths in the safety population | 3 participants |
| Placebo | All Collected Deaths | Total deaths | 3 participants |