COVID-19
Conditions
Keywords
coronavirus, coronavirus infection, safety
Brief summary
The reason for this study is to see if the study drug baricitinib is effective in hospitalized participants with COVID-19.
Interventions
DRUGBaricitinib
Given orally
DRUGPlacebo
Given orally
Sponsors
Eli Lilly and Company
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
DOUBLE (Subject, Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Hospitalized with coronavirus (SARS-CoV-2) infection, confirmed by polymerase chain reaction (PCR) test or other commercial or public health assay in any specimen, as documented by either of the following: * PCR positive in sample collected \<72 hours prior to randomization; OR * PCR positive in sample collected ≥72 hours prior to randomization (but no more than 14 days prior to randomization), documented inability to obtain a repeat sample (for example, due to lack of testing supplies, limited testing capacity, results taking \>24 hours, etc.) AND progressive disease suggestive of ongoing SARS-CoV-2 infection. * Requires supplemental oxygen at the time of study entry and at randomization. * Have indicators of risk of progression: at least 1 inflammatory markers \>upper limit of normal (ULN) (C reactive protein \[CRP\], D dimer, lactate dehydrogenase \[LDH\], ferritin) with at least 1 instance of elevation \>ULN within 2 days before study entry.
Exclusion criteria
* Are receiving cytotoxic or biologic treatments (such as tumor necrosis factor \[TNF\] inhibitors, anti-interleukin-1 \[IL-1\], anti-IL-6 \[tocilizumab or sarilumab\], T-cell or B-cell targeted therapies (rituximab), interferon, or Janus kinase (JAK) inhibitors for any indication at study entry. Note: A washout period 4 weeks (or 5 half-lives, whichever is longer) is required prior to screening. * Have ever received convalescent plasma or intravenous immunoglobulin \[IVIg\]) for COVID-19. * Have received high dose corticosteroids at doses \>20 mg per day (or prednisone equivalent) administered for ≥14 consecutive days in the month prior to study entry. * Strong inhibitors of OAT3 (such as probenecid) that cannot be discontinued at study entry. * Have received neutralizing antibodies, such as bamlanivimab, casirivimab and imdevimab for COVID-19. * Have diagnosis of current active tuberculosis (TB) or, if known, latent TB treated for less than 4 weeks with appropriate anti-tuberculosis therapy per local guidelines (by history only, no screening tests required). * Suspected serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking investigational product. * Have received any live vaccine within 4 weeks before screening, or intend to receive a live vaccine during the study. Note: Use of nonlive (inactivated) vaccinations is allowed for all participants. * Require invasive mechanical ventilation, including extracorporeal membrane oxygenation (ECMO) at study entry. * Current diagnosis of active malignancy that, in the opinion of the investigator, could constitute a risk when taking investigational product. * Have a history of venous thromboembolism (VTE) (deep vein thrombosis \[DVT\] and/or pulmonary embolism \[PE\]) within 12 weeks prior to randomization or have a history of recurrent (\>1) VTE (DVT/PE). * Anticipated discharge from the hospital, or transfer to another hospital (or another unit), which is not a study site within 72 hours after study entry. * Have neutropenia (absolute neutrophil count \<1000 cells/microliters). * Have lymphopenia (absolute lymphocyte count \<200 cells/microliters). * Have alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>5 times ULN. * Estimated glomerular filtration rate (eGFR) (Modification of Diet in Renal Disease \[MDRD\]) \<30 milliliter/minute/1.73 meters squared. * Have a known hypersensitivity to baricitinib or any of its excipients. * Are currently enrolled in any other clinical study involving an investigation product or any other type of medical research judged not to be scientifically or medically compatible with this study. Note: The participant should not be enrolled (started) in another clinical trial for the treatment of COVID-19 or SARS CoV-2 through Day 28. * Are pregnant, or intend to become pregnant or breastfeed during the study. * Are using or will use extracorporeal blood purification (EBP) device to remove proinflammatory cytokines from the blood such as a cytokine absorption or filtering device, for example, CytoSorb®. * Are, in the opinion of the investigator, unlikely to survive for at least 48 hours after screening.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (Including Extracorporeal Membrane Oxygenation [ECMO]) | Day 1 to Day 28 | Percentage of participants who die or require non-invasive ventilation/high-flow oxygen or invasive mechanical ventilation (including ECMO). |
| Percentage of Participants Who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (Including Extracorporeal Membrane Oxygenation [ECMO] Population 2 | Day 1 to Day 28 | Percentage of participants who die or require non-invasive ventilation or invasive mechanical ventilation, including ECMO. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time to Recovery | Day 1 to Day 28 | Recovery assessed by the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS). Time to reach NIAID-OS 1, 2, or 3 for the first time. The date reached is the first full day that OS 1, 2, or 3 is the participant's maximum OS for the day. NIAID-OS 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities and/or requiring home oxygen 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care: (This would include those kept in hospital for quarantine/infection control, awaiting bed in rehabilitation facility or homecare, etc.) |
| Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 4 | Day 4 | Overall improvement on the National Institute of Allergy and Infectious Diseases ordinal scale: 1\. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care: (This would include those kept in hospital for quarantine/infection control, awaiting bed in rehabilitation facility or homecare, etc.); 4. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5. Hospitalized, requiring supplemental oxygen; 6.Hospitalized, on noninvasive ventilation or high-flow oxygen devices; 7. Hospitalized, on invasive mechanical ventilation or ECMO; 8. Death. |
| Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 7 | Day 7 | Overall improvement on the National Institute of Allergy and Infectious Diseases ordinal scale: 1\. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care: (This would include those kept in hospital for quarantine/infection control, awaiting bed in rehabilitation facility or homecare, etc.); 4. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5. Hospitalized, requiring supplemental oxygen; 6.Hospitalized, on noninvasive ventilation or high-flow oxygen devices; 7. Hospitalized, on invasive mechanical ventilation or ECMO; 8. Death. |
| Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 10 | Day 10 | Overall improvement on the National Institute of Allergy and Infectious Diseases ordinal scale: 1\. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care: (This would include those kept in hospital for quarantine/infection control, awaiting bed in rehabilitation facility or homecare, etc.); 4. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5. Hospitalized, requiring supplemental oxygen; 6.Hospitalized, on noninvasive ventilation or high-flow oxygen devices; 7. Hospitalized, on invasive mechanical ventilation or ECMO; 8. Death. |
| Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 14 | Day 14 | Overall improvement on the National Institute of Allergy and Infectious Diseases ordinal scale: 1\. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care: (This would include those kept in hospital for quarantine/infection control, awaiting bed in rehabilitation facility or homecare, etc.); 4. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5. Hospitalized, requiring supplemental oxygen; 6.Hospitalized, on noninvasive ventilation or high-flow oxygen devices; 7. Hospitalized, on invasive mechanical ventilation or ECMO; 8. Death. |
| Duration of Hospitalization | Days 1 to Day 28 | Duration of hospitalization. |
| Percentage of Participants With a Change in Oxygen Saturation From < 94% to ≥ 94% From Baseline | Day 10 | Percentage of participants with a change in oxygen saturation from \< 94% to ≥ 94% from baseline based on National Early Warning Score (NEWS). Measure of the oxygen level of the blood is measure by pulse oximetry. The score is determined from six physiological parameters readily measured over time in hospitalized participants: Respiration rate; oxygen saturation; temperature; systolic blood pressure; heart (pulse) rate, and level of consciousness, as measured by Alert Voice Pain Unresponsive (AVPU). A score is assigned to each parameter, the magnitude of the score representing the extremity of variation from the norm. A weighting score is added for participants needing supplemental oxygen (oxygen delivery by mask or by cannula) The aggregate score is reflective of the participants status. |
| Overall Mortality | Day 1 to Day 28 | Number of deaths by Day 28. |
| Percentage of Participants With at Least 1-Point Improvement on National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) or Live Discharge From Hospital | Day 10 | The National Institute of Allergy and Infectious Diseases ordinal scale (NIAID-OS) is an assessment of clinical status. The scale is as follows: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 8) Death. Participants with missing baseline ordinal scale values were excluded from analysis. |
| Time to Clinical Deterioration (One-category Increase on the NIAID-OS) | Day 1 to Day 28 | The National Institute of Allergy and Infectious Diseases ordinal scale (NIAID-OS) is an assessment of clinical status. The scale is as follows: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 8) Death. A higher score is representative of worse clinical outcome with a score of 8 being the highest and representing death. |
| Time to Resolution of Fever in Participants With Fever at Baseline | Day 1 to Day 28 | Time to resolution of fever in participants with fever at baseline was calculated using cox proportional hazard regression model adjusted for baseline disease severity (OS 4, OS 5, OS 6), age (\<65 years, \>=65 years), region (United States, Europe, rest of world), and systemic corticosteroids used at baseline for primary study condition (Yes/No). |
| Mean Change From Baseline on the National Early Warning Score (NEWS) | Baseline, Day 4; Baseline, Day 7; Baseline, Day 10; Baseline, Day 14 | The NEWS score is used to detect and report changes in illness severity in participants with acute illness to identify participants at risk for poor outcomes. The score is based on six physiological parameters (Respiration rate; oxygen saturation; temperature; systolic blood pressure; heart (pulse) rate, and level of consciousness). A score is assigned to each parameter, and the sum of the score represents the participant's risk of poor outcomes with a minimum score of 0 representing the better outcome, a score of 7 or greater reflects high clinical risk for worsening and maximum score of 19 representing the worse outcome. |
| Time to Definitive Extubation | Day 1 to Day 28 | Time to definitive extubation included participants who progressed to OS 7 at any time prior to Day 28. |
| Time to Independence From Non-Invasive Mechanical Ventilation | Day 1 to Day 28 | Time to independence from non-invasive mechanical ventilation was measured in days among participants who required non-invasive ventilation. |
| Time to Independence From Oxygen Therapy in Days | Day 1 to Day 28 | Time to independence from oxygen therapy in days. |
| Number of Days With Supplemental Oxygen Use | Day 1 to Day 28 | Number of days with supplemental oxygen use. |
| Number of Days of Resting Respiratory Rate <24 Breaths Per Minute | Day 1 to Day 28 | Number of days of resting respiratory rate \<24 breaths per minute. |
| Duration of Stay in the Intensive Care Unit (ICU) in Days | Day 1 to Day 28 | Duration of stay in the ICU in days. |
| Number of Ventilator-Free Days | Day 1 to Day 28 | Number of days free of invasive mechanical ventilation. |
Countries
Argentina, Brazil, Germany, India, Italy, Japan, Mexico, Puerto Rico, Russia, South Korea, Spain, United Kingdom, United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Placebo +SOC Placebo administered orally QD with standard of care. | 761 |
| Baricitinib + SOC 4 mg baricitinib administered orally QD with standard of care. | 764 |
| Total | 1,525 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Follow-Up Period | Adverse Event | 0 | 0 | 0 | 3 |
| Follow-Up Period | Death | 0 | 0 | 16 | 17 |
| Follow-Up Period | Left message, participant did not call back | 0 | 0 | 0 | 1 |
| Follow-Up Period | Lost to Follow-up | 0 | 0 | 7 | 7 |
| Follow-Up Period | Participant died | 0 | 0 | 0 | 1 |
| Follow-Up Period | Participant was alive but did not respond to calls | 0 | 0 | 0 | 1 |
| Follow-Up Period | Protocol Deviation | 0 | 0 | 1 | 0 |
| Follow-Up Period | Still in hospital on ventilator at end of study | 0 | 0 | 1 | 0 |
| Treatment Period | Adverse Event | 5 | 3 | 0 | 0 |
| Treatment Period | Death | 98 | 61 | 0 | 0 |
| Treatment Period | Lost to Follow-up | 22 | 20 | 0 | 0 |
| Treatment Period | Other-Unknown | 15 | 9 | 0 | 0 |
| Treatment Period | Physician Decision | 1 | 1 | 0 | 0 |
| Treatment Period | Randomized Not Dosed | 9 | 14 | 0 | 0 |
| Treatment Period | Withdrawal by Subject | 7 | 12 | 0 | 0 |
Baseline characteristics
| Characteristic | Placebo +SOC | Baricitinib + SOC | Total |
|---|---|---|---|
| Age, Continuous | 57.5 years STANDARD_DEVIATION 13.8 | 57.8 years STANDARD_DEVIATION 14.3 | 57.6 years STANDARD_DEVIATION 14.1 |
| Race (NIH/OMB) American Indian or Alaska Native | 168 Participants | 148 Participants | 316 Participants |
| Race (NIH/OMB) Asian | 94 Participants | 80 Participants | 174 Participants |
| Race (NIH/OMB) Black or African American | 36 Participants | 39 Participants | 75 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants | 3 Participants | 5 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 20 Participants | 12 Participants | 32 Participants |
| Race (NIH/OMB) White | 440 Participants | 480 Participants | 920 Participants |
| Region of Enrollment Argentina | 101 Participants | 107 Participants | 208 Participants |
| Region of Enrollment Brazil | 165 Participants | 172 Participants | 337 Participants |
| Region of Enrollment Germany | 11 Participants | 9 Participants | 20 Participants |
| Region of Enrollment India | 31 Participants | 19 Participants | 50 Participants |
| Region of Enrollment Italy | 10 Participants | 15 Participants | 25 Participants |
| Region of Enrollment Japan | 19 Participants | 19 Participants | 38 Participants |
| Region of Enrollment Mexico | 143 Participants | 138 Participants | 281 Participants |
| Region of Enrollment Puerto Rico | 3 Participants | 8 Participants | 11 Participants |
| Region of Enrollment Russia | 54 Participants | 58 Participants | 112 Participants |
| Region of Enrollment South Korea | 20 Participants | 16 Participants | 36 Participants |
| Region of Enrollment Spain | 42 Participants | 45 Participants | 87 Participants |
| Region of Enrollment United Kingdom | 7 Participants | 4 Participants | 11 Participants |
| Region of Enrollment United States | 155 Participants | 154 Participants | 309 Participants |
| Sex: Female, Male Female | 288 Participants | 274 Participants | 562 Participants |
| Sex: Female, Male Male | 473 Participants | 490 Participants | 963 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 104 / 752 | 65 / 750 | 16 / 613 | 18 / 645 |
| other Total, other adverse events | 0 / 752 | 0 / 750 | 0 / 613 | 0 / 645 |
| serious Total, serious adverse events | 135 / 752 | 110 / 750 | 12 / 613 | 18 / 645 |
Outcome results
Primary
Percentage of Participants Who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (Including Extracorporeal Membrane Oxygenation [ECMO])
Percentage of participants who die or require non-invasive ventilation/high-flow oxygen or invasive mechanical ventilation (including ECMO).
Time frame: Day 1 to Day 28
Population: All participants randomly assigned to study intervention. Participants with missing baseline ordinal scale values were excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + SOC | Percentage of Participants Who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (Including Extracorporeal Membrane Oxygenation [ECMO]) | 30.5 percentage of participants |
| Baricitinib + SOC | Percentage of Participants Who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (Including Extracorporeal Membrane Oxygenation [ECMO]) | 27.8 percentage of participants |
p-value: 0.1895% CI: [0.67, 1.08]Regression, Logistic
Primary
Percentage of Participants Who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (Including Extracorporeal Membrane Oxygenation [ECMO] Population 2
Percentage of participants who die or require non-invasive ventilation or invasive mechanical ventilation, including ECMO.
Time frame: Day 1 to Day 28
Population: All participants randomly assigned to study intervention who at baseline required oxygen supplementation and did not receive dexamethasone, or other systemic corticosteroids for the primary study condition.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + SOC | Percentage of Participants Who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (Including Extracorporeal Membrane Oxygenation [ECMO] Population 2 | 27.1 percentage of participants |
| Baricitinib + SOC | Percentage of Participants Who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (Including Extracorporeal Membrane Oxygenation [ECMO] Population 2 | 28.9 percentage of participants |
p-value: 0.72895% CI: [0.58, 2.16]Regression, Logistic
Secondary
Duration of Hospitalization
Duration of hospitalization.
Time frame: Days 1 to Day 28
Population: All participants randomly assigned to study intervention. Participants with missing baseline ordinal scale were excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + SOC | Duration of Hospitalization | 13.7 days | Standard Error 0.4 |
| Baricitinib + SOC | Duration of Hospitalization | 12.9 days | Standard Error 0.4 |
p-value: 0.062695% CI: [-1.6, 0]ANOVA
Secondary
Duration of Stay in the Intensive Care Unit (ICU) in Days
Duration of stay in the ICU in days.
Time frame: Day 1 to Day 28
Population: All participants randomly assigned to study intervention with non-missing baseline NIAID OS and at least 1 postbaseline NIAID OS observation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + SOC | Duration of Stay in the Intensive Care Unit (ICU) in Days | 3.17 days | Standard Error 0.313 |
| Baricitinib + SOC | Duration of Stay in the Intensive Care Unit (ICU) in Days | 3.19 days | Standard Error 0.315 |
p-value: 0.952695% CI: [-0.62, 0.65]ANOVA
Secondary
Mean Change From Baseline on the National Early Warning Score (NEWS)
The NEWS score is used to detect and report changes in illness severity in participants with acute illness to identify participants at risk for poor outcomes. The score is based on six physiological parameters (Respiration rate; oxygen saturation; temperature; systolic blood pressure; heart (pulse) rate, and level of consciousness). A score is assigned to each parameter, and the sum of the score represents the participant's risk of poor outcomes with a minimum score of 0 representing the better outcome, a score of 7 or greater reflects high clinical risk for worsening and maximum score of 19 representing the worse outcome.
Time frame: Baseline, Day 4; Baseline, Day 7; Baseline, Day 10; Baseline, Day 14
Population: All participants randomly assigned to study intervention with baseline and 1 postbaseline observation.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| Placebo + SOC | Mean Change From Baseline on the National Early Warning Score (NEWS) | Day 4 | -0.59 score on a scale | Standard Error 0.127 |
| Placebo + SOC | Mean Change From Baseline on the National Early Warning Score (NEWS) | Day 7 | -0.86 score on a scale | Standard Error 0.145 |
| Placebo + SOC | Mean Change From Baseline on the National Early Warning Score (NEWS) | Day 10 | -1.33 score on a scale | Standard Error 0.16 |
| Placebo + SOC | Mean Change From Baseline on the National Early Warning Score (NEWS) | Day 14 | -1.41 score on a scale | Standard Error 0.183 |
| Baricitinib + SOC | Mean Change From Baseline on the National Early Warning Score (NEWS) | Day 14 | -1.66 score on a scale | Standard Error 0.182 |
| Baricitinib + SOC | Mean Change From Baseline on the National Early Warning Score (NEWS) | Day 4 | -0.76 score on a scale | Standard Error 0.125 |
| Baricitinib + SOC | Mean Change From Baseline on the National Early Warning Score (NEWS) | Day 10 | -1.45 score on a scale | Standard Error 0.158 |
| Baricitinib + SOC | Mean Change From Baseline on the National Early Warning Score (NEWS) | Day 7 | -1.04 score on a scale | Standard Error 0.143 |
Comparison: Day 4p-value: 0.19195% CI: [-0.42, 0.08]Mixed Models Analysis
Comparison: Day 7p-value: 0.27895% CI: [-0.49, 0.14]Mixed Models Analysis
Comparison: Day 10p-value: 0.49695% CI: [-0.49, 0.24]Mixed Models Analysis
Comparison: Day 14p-value: 0.26395% CI: [-0.7, 0.19]Mixed Models Analysis
Secondary
Number of Days of Resting Respiratory Rate <24 Breaths Per Minute
Number of days of resting respiratory rate \<24 breaths per minute.
Time frame: Day 1 to Day 28
Population: All participants randomly assigned to study intervention who had non-missing baseline and at least 1 postbaseline respiratory rate.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + SOC | Number of Days of Resting Respiratory Rate <24 Breaths Per Minute | 9.62 days | Standard Error 0.3 |
| Baricitinib + SOC | Number of Days of Resting Respiratory Rate <24 Breaths Per Minute | 9.73 days | Standard Error 0.304 |
p-value: 0.707395% CI: [-0.49, 0.72]ANOVA
Secondary
Number of Days With Supplemental Oxygen Use
Number of days with supplemental oxygen use.
Time frame: Day 1 to Day 28
Population: All participants randomly assigned to study intervention who have non-missing baseline and at least 1 postbaseline observation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + SOC | Number of Days With Supplemental Oxygen Use | 4.60 days | Standard Error 0.221 |
| Baricitinib + SOC | Number of Days With Supplemental Oxygen Use | 4.37 days | Standard Error 0.222 |
p-value: 0.305895% CI: [-0.68, 0.21]ANOVA
Secondary
Number of Ventilator-Free Days
Number of days free of invasive mechanical ventilation.
Time frame: Day 1 to Day 28
Population: All participants randomly assigned to study intervention. Participants with missing baseline ordinal scale values were excluded.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| Placebo + SOC | Number of Ventilator-Free Days | 23.7 days | Standard Error 0.39 |
| Baricitinib + SOC | Number of Ventilator-Free Days | 24.5 days | Standard Error 0.39 |
p-value: 0.058695% CI: [0, 1.5]ANOVA
Secondary
Overall Mortality
Number of deaths by Day 28.
Time frame: Day 1 to Day 28
Population: All participants randomly assigned to study intervention.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + SOC | Overall Mortality | 104 event of death |
| Baricitinib + SOC | Overall Mortality | 65 event of death |
p-value: 0.001895% CI: [0.41, 0.78]Log Rank
Secondary
Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 10
Overall improvement on the National Institute of Allergy and Infectious Diseases ordinal scale: 1\. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care: (This would include those kept in hospital for quarantine/infection control, awaiting bed in rehabilitation facility or homecare, etc.); 4. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5. Hospitalized, requiring supplemental oxygen; 6.Hospitalized, on noninvasive ventilation or high-flow oxygen devices; 7. Hospitalized, on invasive mechanical ventilation or ECMO; 8. Death.
Time frame: Day 10
Population: All participants randomly assigned to study intervention. Participants with missing baseline ordinal scale were excluded.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 10 | Day 10 NIAID-OS 5 | 12.8 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 10 | Day 10 NIAID-OS 2 | 9.4 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 10 | Day 10 NIAID-OS 6 | 8.1 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 10 | Day 10 NIAID-OS 1 | 37.7 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 10 | Day 10 NIAID-OS 7 | 10.6 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 10 | Day 10 NIAID-OS 3 | 0.1 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 10 | Day 10 NIAID-OS 8 | 5.1 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 10 | Day 10 NIAID-OS 4 | 16.2 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 10 | Day 10 NIAID-OS 8 | 2.6 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 10 | Day 10 NIAID-OS 4 | 14.1 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 10 | Day 10 NIAID-OS 1 | 40.4 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 10 | Day 10 NIAID-OS 2 | 10.9 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 10 | Day 10 NIAID-OS 5 | 12.4 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 10 | Day 10 NIAID-OS 6 | 8.9 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 10 | Day 10 NIAID-OS 7 | 10.4 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 10 | Day 10 NIAID-OS 3 | 0.1 percentage of participants |
p-value: 0.092195% CI: [0.97, 1.41]Proportional Odds Model
Secondary
Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 14
Overall improvement on the National Institute of Allergy and Infectious Diseases ordinal scale: 1\. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care: (This would include those kept in hospital for quarantine/infection control, awaiting bed in rehabilitation facility or homecare, etc.); 4. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5. Hospitalized, requiring supplemental oxygen; 6.Hospitalized, on noninvasive ventilation or high-flow oxygen devices; 7. Hospitalized, on invasive mechanical ventilation or ECMO; 8. Death.
Time frame: Day 14
Population: All participants randomly assigned to study intervention. Participants with missing baseline ordinal scale were excluded.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 14 | Day 14 NIAID-OS 1 | 51.6 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 14 | Day 14 NIAID-OS 2 | 11.2 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 14 | Day 14 NIAID-OS 3 | 0.3 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 14 | Day 14 NIAID-OS 4 | 8.0 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 14 | Day 14 NIAID-OS 5 | 8.4 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 14 | Day 14 NIAID-OS 6 | 3.6 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 14 | Day 14 NIAID-OS 7 | 9.4 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 14 | Day 14 NIAID-OS 8 | 7.5 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 14 | Day 14 NIAID-OS 8 | 4.9 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 14 | Day 14 NIAID-OS 1 | 56.3 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 14 | Day 14 NIAID-OS 5 | 7.3 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 14 | Day 14 NIAID-OS 2 | 11.1 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 14 | Day 14 NIAID-OS 7 | 8.9 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 14 | Day 14 NIAID-OS 3 | 0.1 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 14 | Day 14 NIAID-OS 6 | 3.7 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 14 | Day 14 NIAID-OS 4 | 7.6 percentage of participants |
p-value: 0.016895% CI: [1.05, 1.56]Proportional Odds Model
Secondary
Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 4
Overall improvement on the National Institute of Allergy and Infectious Diseases ordinal scale: 1\. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care: (This would include those kept in hospital for quarantine/infection control, awaiting bed in rehabilitation facility or homecare, etc.); 4. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5. Hospitalized, requiring supplemental oxygen; 6.Hospitalized, on noninvasive ventilation or high-flow oxygen devices; 7. Hospitalized, on invasive mechanical ventilation or ECMO; 8. Death.
Time frame: Day 4
Population: All participants randomly assigned to study intervention. Participants with missing baseline ordinal scale were excluded.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 4 | Day 4 NIAID-OS 1 | 4.6 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 4 | Day 4 NIAID-OS 5 | 41.0 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 4 | Day 4 NIAID-OS 3 | 0.8 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 4 | Day 4 NIAID-OS 6 | 22.4 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 4 | Day 4 NIAID-OS 2 | 1.5 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 4 | Day 4 NIAID-OS 7 | 8.9 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 4 | Day 4 NIAID-OS 8 | 1.4 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 4 | Day 4 NIAID-OS 4 | 19.4 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 4 | Day 4 NIAID-OS 8 | 0.4 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 4 | Day 4 NIAID-OS 1 | 5.2 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 4 | Day 4 NIAID-OS 2 | 1.5 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 4 | Day 4 NIAID-OS 3 | 0.3 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 4 | Day 4 NIAID-OS 4 | 23.6 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 4 | Day 4 NIAID-OS 5 | 39.0 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 4 | Day 4 NIAID-OS 6 | 21.8 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 4 | Day 4 NIAID-OS 7 | 8.1 percentage of participants |
Comparison: Day 4p-value: 0.046495% CI: [1, 1.47]Proportional Odds Model
Secondary
Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 7
Overall improvement on the National Institute of Allergy and Infectious Diseases ordinal scale: 1\. Not hospitalized, no limitations on activities; 2. Not hospitalized, limitation on activities and/or requiring home oxygen; 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care: (This would include those kept in hospital for quarantine/infection control, awaiting bed in rehabilitation facility or homecare, etc.); 4. Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5. Hospitalized, requiring supplemental oxygen; 6.Hospitalized, on noninvasive ventilation or high-flow oxygen devices; 7. Hospitalized, on invasive mechanical ventilation or ECMO; 8. Death.
Time frame: Day 7
Population: All participants randomly assigned to study intervention. Participants with missing baseline ordinal scale were excluded.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 7 | Day 7 NIAID-OS 1 | 20.2 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 7 | Day 7 NIAID-OS 2 | 6.6 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 7 | Day 7 NIAID-OS 3 | 0.5 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 7 | Day 7 NIAID-OS 4 | 21.2 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 7 | Day 7 NIAID-OS 5 | 22.5 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 7 | Day 7 NIAID-OS 6 | 14.5 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 7 | Day 7 NIAID-OS 7 | 11.2 percentage of participants |
| Placebo + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 7 | Day 7 NIAID-OS 8 | 3.3 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 7 | Day 7 NIAID-OS 8 | 1.2 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 7 | Day 7 NIAID-OS 1 | 25.2 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 7 | Day 7 NIAID-OS 5 | 22.5 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 7 | Day 7 NIAID-OS 2 | 5.8 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 7 | Day 7 NIAID-OS 7 | 10.8 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 7 | Day 7 NIAID-OS 3 | 0.2 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 7 | Day 7 NIAID-OS 6 | 13.8 percentage of participants |
| Baricitinib + SOC | Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 7 | Day 7 NIAID-OS 4 | 20.6 percentage of participants |
p-value: 0.017295% CI: [1.04, 1.49]Proportional Odds Model
Secondary
Percentage of Participants With a Change in Oxygen Saturation From < 94% to ≥ 94% From Baseline
Percentage of participants with a change in oxygen saturation from \< 94% to ≥ 94% from baseline based on National Early Warning Score (NEWS). Measure of the oxygen level of the blood is measure by pulse oximetry. The score is determined from six physiological parameters readily measured over time in hospitalized participants: Respiration rate; oxygen saturation; temperature; systolic blood pressure; heart (pulse) rate, and level of consciousness, as measured by Alert Voice Pain Unresponsive (AVPU). A score is assigned to each parameter, the magnitude of the score representing the extremity of variation from the norm. A weighting score is added for participants needing supplemental oxygen (oxygen delivery by mask or by cannula) The aggregate score is reflective of the participants status.
Time frame: Day 10
Population: All participants randomly assigned to study intervention whose oxygen saturation (based on National Early Warning Score) is \< 94% at baseline and have non-missing baseline and at least 1 postbaseline observation are in this population.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + SOC | Percentage of Participants With a Change in Oxygen Saturation From < 94% to ≥ 94% From Baseline | 52.5 percentage of participants |
| Baricitinib + SOC | Percentage of Participants With a Change in Oxygen Saturation From < 94% to ≥ 94% From Baseline | 56.7 percentage of participants |
p-value: 0.42995% CI: [0.81, 1.63]Regression, Logistic
Secondary
Percentage of Participants With at Least 1-Point Improvement on National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) or Live Discharge From Hospital
The National Institute of Allergy and Infectious Diseases ordinal scale (NIAID-OS) is an assessment of clinical status. The scale is as follows: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 8) Death. Participants with missing baseline ordinal scale values were excluded from analysis.
Time frame: Day 10
Population: All participants randomly assigned to study intervention. Participants with missing baseline ordinal scale values were excluded.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Placebo + SOC | Percentage of Participants With at Least 1-Point Improvement on National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) or Live Discharge From Hospital | 63.5 percentage of participants |
| Baricitinib + SOC | Percentage of Participants With at Least 1-Point Improvement on National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) or Live Discharge From Hospital | 65.0 percentage of participants |
p-value: 0.544495% CI: [0.86, 1.34]Regression, Logistic
Secondary
Time to Clinical Deterioration (One-category Increase on the NIAID-OS)
The National Institute of Allergy and Infectious Diseases ordinal scale (NIAID-OS) is an assessment of clinical status. The scale is as follows: 1) Not hospitalized, no limitations on activities; 2) Not hospitalized, limitation on activities and/or requiring home oxygen; 3) Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care; 4) Hospitalized, not requiring supplemental oxygen - requiring ongoing medical care (COVID-19 related or otherwise); 5) Hospitalized, requiring supplemental oxygen; 6) Hospitalized, on non-invasive ventilation or high-flow oxygen devices; 7) Hospitalized, on invasive mechanical ventilation or ECMO; 8) Death. A higher score is representative of worse clinical outcome with a score of 8 being the highest and representing death.
Time frame: Day 1 to Day 28
Population: All participants randomly assigned to study intervention. Participants with missing baseline ordinal scale values were excluded from analysis.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + SOC | Time to Clinical Deterioration (One-category Increase on the NIAID-OS) | NA days |
| Baricitinib + SOC | Time to Clinical Deterioration (One-category Increase on the NIAID-OS) | NA days |
p-value: 0.183195% CI: [0.741, 1.061]Log Rank
Secondary
Time to Definitive Extubation
Time to definitive extubation included participants who progressed to OS 7 at any time prior to Day 28.
Time frame: Day 1 to Day 28
Population: All participants randomly assigned to study intervention who were intubated at some point during the study.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + SOC | Time to Definitive Extubation | NA days |
| Baricitinib + SOC | Time to Definitive Extubation | NA days |
Secondary
Time to Independence From Non-Invasive Mechanical Ventilation
Time to independence from non-invasive mechanical ventilation was measured in days among participants who required non-invasive ventilation.
Time frame: Day 1 to Day 28
Population: All participants randomly assigned to study intervention whose baseline OS was 6 and were on non-invasive mechanical ventilation.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + SOC | Time to Independence From Non-Invasive Mechanical Ventilation | 11.00 days |
| Baricitinib + SOC | Time to Independence From Non-Invasive Mechanical Ventilation | 12.00 days |
p-value: 0.6436Log Rank
Secondary
Time to Independence From Oxygen Therapy in Days
Time to independence from oxygen therapy in days.
Time frame: Day 1 to Day 28
Population: All randomized participants who had an ordinal scale score of 5 or 6 at baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + SOC | Time to Independence From Oxygen Therapy in Days | 8.00 days |
| Baricitinib + SOC | Time to Independence From Oxygen Therapy in Days | 8.00 days |
p-value: 0.127Log Rank
Secondary
Time to Recovery
Recovery assessed by the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS). Time to reach NIAID-OS 1, 2, or 3 for the first time. The date reached is the first full day that OS 1, 2, or 3 is the participant's maximum OS for the day. NIAID-OS 1. Not hospitalized, no limitations on activities 2. Not hospitalized, limitation on activities and/or requiring home oxygen 3. Hospitalized, not requiring supplemental oxygen - no longer requires ongoing medical care: (This would include those kept in hospital for quarantine/infection control, awaiting bed in rehabilitation facility or homecare, etc.)
Time frame: Day 1 to Day 28
Population: All participants randomly assigned to study intervention.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + SOC | Time to Recovery | 11.0 days |
| Baricitinib + SOC | Time to Recovery | 10.0 days |
p-value: 0.145395% CI: [0.99, 1.24]Log Rank
Secondary
Time to Resolution of Fever in Participants With Fever at Baseline
Time to resolution of fever in participants with fever at baseline was calculated using cox proportional hazard regression model adjusted for baseline disease severity (OS 4, OS 5, OS 6), age (\<65 years, \>=65 years), region (United States, Europe, rest of world), and systemic corticosteroids used at baseline for primary study condition (Yes/No).
Time frame: Day 1 to Day 28
Population: All participants randomly assigned to study intervention who had a fever at baseline.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Placebo + SOC | Time to Resolution of Fever in Participants With Fever at Baseline | 4.00 days |
| Baricitinib + SOC | Time to Resolution of Fever in Participants With Fever at Baseline | 3.00 days |
p-value: 0.024395% CI: [1.017, 1.421]Log Rank