A Study of Baricitinib (LY3009104) in Participants With COVID-19 (COV-BARRIER)
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The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. |
| ClinicalTrials.gov Identifier: NCT04421027 |
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Recruitment Status :
Completed
First Posted : June 9, 2020
Results First Posted : March 24, 2022
Last Update Posted : July 28, 2022
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| COVID-19 | Drug: Baricitinib Drug: Placebo | Phase 3 |
| Study Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 1525 participants |
| Allocation: | Randomized |
| Intervention Model: | Parallel Assignment |
| Masking: | Double (Participant, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase 3 Study of Baricitinib in Patients With COVID-19 Infection |
| Actual Study Start Date : | June 12, 2020 |
| Actual Primary Completion Date : | February 12, 2021 |
| Actual Study Completion Date : | June 10, 2021 |
| Arm | Intervention/treatment |
|---|---|
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Experimental: Baricitinib + Standard of Care (SOC)
4 milligrams (mg) of baricitinib (given as two 2 mg tablets) administered orally every day (QD) with standard of care.
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Drug: Baricitinib
Given orally
Other Name: LY3009104 |
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Placebo Comparator: Placebo + SOC
Placebo (given as two placebo tablets) administered orally QD with standard of care.
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Drug: Placebo
Given orally |
- Percentage of Participants Who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (Including Extracorporeal Membrane Oxygenation [ECMO]) [ Time Frame: 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 [ Time Frame: Day 1 to Day 28 ]Percentage of participants who die or require non-invasive ventilation or invasive mechanical ventilation, including ECMO.
- 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 [ Time Frame: 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.
- Number of Ventilator-Free Days [ Time Frame: Day 1 to Day 28 ]Number of days free of invasive mechanical ventilation.
- Time to Recovery [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Days 1 to Day 28 ]Duration of hospitalization.
- Percentage of Participants With a Change in Oxygen Saturation From < 94% to ≥ 94% From Baseline [ Time Frame: 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 [ Time Frame: Day 1 to Day 28 ]Number of deaths by Day 28.
- Duration of Stay in the Intensive Care Unit (ICU) in Days [ Time Frame: Day 1 to Day 28 ]Duration of stay in the ICU in days.
- Time to Clinical Deterioration (One-category Increase on the NIAID-OS) [ Time Frame: 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 [ Time Frame: 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) [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: Day 1 to Day 28 ]Time to independence from oxygen therapy in days.
- Number of Days With Supplemental Oxygen Use [ Time Frame: Day 1 to Day 28 ]Number of days with supplemental oxygen use.
- Number of Days of Resting Respiratory Rate <24 Breaths Per Minute [ Time Frame: Day 1 to Day 28 ]Number of days of resting respiratory rate <24 breaths per minute.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.
| Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
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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.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04421027
Show 96 study locations
| Study Director: | Call 1-877-CTLILLY (1-877-265-4559 or 1-317-615-4559) Mon - Fri 9AM - 5PM Eastern Time (UTC/GMT - 5 hours, EST) | Eli Lilly and Company |
Documents provided by Eli Lilly and Company:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Eli Lilly and Company |
| ClinicalTrials.gov Identifier: | NCT04421027 |
| Other Study ID Numbers: |
17830 I4V-MC-KHAA ( Other Identifier: Eli Lilly and Company ) 2020-001517-21 ( EudraCT Number ) |
| First Posted: | June 9, 2020 Key Record Dates |
| Results First Posted: | March 24, 2022 |
| Last Update Posted: | July 28, 2022 |
| Last Verified: | July 2022 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Anonymized individual patient level data will be provided in a secure access environment upon approval of a research proposal and a signed data sharing agreement |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (SAP) Clinical Study Report (CSR) |
| Time Frame: | Data are available 6 months after the primary publication and approval of the indication studied in the US and European Union (EU), whichever is later. Data will be indefinitely available for requesting |
| Access Criteria: | Data are available 6 months after the primary publication and approval of the indication studied in the US and EU, whichever is later. Data will be indefinitely available for requesting |
| URL: | http://vivli.org/ |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
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coronavirus coronavirus infection safety |
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COVID-19 Pneumonia, Viral Pneumonia Respiratory Tract Infections Infections Virus Diseases |
Coronavirus Infections Coronaviridae Infections Nidovirales Infections RNA Virus Infections Lung Diseases Respiratory Tract Diseases |