A Study of Baricitinib (LY3009104) in Participants With COVID-19
- Registration Number
- NCT04421027
- Lead Sponsor
- Eli Lilly and Company
- Brief Summary
The reason for this study is to see if the study drug baricitinib is effective in hospitalized participants with COVID-19.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 1525
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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.
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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.
- 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.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Placebo + SOC Placebo Placebo (given as two placebo tablets) administered orally QD with standard of care. Baricitinib + Standard of Care (SOC) Baricitinib 4 milligrams (mg) of baricitinib (given as two 2 mg tablets) administered orally every day (QD) with standard of care.
- Primary Outcome Measures
Name Time Method 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 Outcome Measures
Name Time Method 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.
Number of Ventilator-Free Days Day 1 to Day 28 Number of days free of invasive mechanical ventilation.
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.
Duration of Stay in the Intensive Care Unit (ICU) in Days Day 1 to Day 28 Duration of stay in the ICU in days.
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).
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.
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.
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.
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.
Trial Locations
- Locations (96)
Grady Health System
🇺🇸Atlanta, Georgia, United States
Westchester General Hospital
🇺🇸Miami, Florida, United States
Community Hospital South
🇺🇸Indianapolis, Indiana, United States
Franciscan St. Francis Health
🇺🇸Indianapolis, Indiana, United States
Sir Ganga Ram Hospital
🇮🇳New Delhi, Delhi, India
Swedish Medical Center
🇺🇸Seattle, Washington, United States
Tokyo Medical University Hachioji Medical Center
🇯🇵Hachioji, Tokyo, Japan
Ruby Hall Clinic and Grant Medical Foundation
🇮🇳Pune, Maharashtra, India
Edogawa Medicare Hospital
🇯🇵Edagawa, Tokyo, Japan
Instituto Nacional de Ciencias Medicas y Nutrici Salva Zubir
🇲🇽Mexico City, Federal District, Mexico
Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
🇲🇽Monterrey, Nuevo León, Mexico
Hospital General Agustín O'Horán
🇲🇽Yucatan, Merida, Mexico
ITESM Campus Monterrey
🇲🇽Monterrey, Nuevo Leon, Mexico
Government Medical College
🇮🇳Nagpur, Maharashtra, India
Hospital Carlos Fernando Malzoni Matao
🇧🇷Matao, Sao Paulo, Brazil
Faculdade de Medicina do ABC
🇧🇷Santo Andre, SP, Brazil
Real e Benemerita Associação Portuguesa de Beneficiencia
🇧🇷São Paulo, Brazil
Valleywise Health
🇺🇸Phoenix, Arizona, United States
Dignity Health Mercy Gilbert Medical Center
🇺🇸Gilbert, Arizona, United States
Hoag Memorial Hospital Presbyterian
🇺🇸Newport Beach, California, United States
Torrance Memorial Medical Center
🇺🇸Torrance, California, United States
Holy Cross Hospital Inc.
🇺🇸Fort Lauderdale, Florida, United States
Renown Regional Med. Center
🇺🇸Reno, Nevada, United States
East Carolina University
🇺🇸Greenville, North Carolina, United States
Sharp Memorial Hospital
🇺🇸San Diego, California, United States
SUNY Downstate
🇺🇸Brooklyn, New York, United States
Atlanta VA Medical Center
🇺🇸Decatur, Georgia, United States
MultiCare Good Samaritan Hospital
🇺🇸Tacoma, Washington, United States
CPCLIN
🇧🇷Natal, Rio Grande Do Norte, Brazil
INMI Lazzaro Spallanzani
🇮🇹Roma, Rome, Italy
Universitätsklinikum Erlangen
🇩🇪Erlangen, Bayern, Germany
Hospital Felício Rocho
🇧🇷Belo Horizonte, Minas Gerais, Brazil
CEPETI Centro de Ensino e Pesquisa em Terapia Intensiva
🇧🇷Curitiba, Paraná, Brazil
Government Medical College (GMC) Aurangabad
🇮🇳Aurangabad, Maharashtra, India
Klinikum Chemnitz gGmbH
🇩🇪Chemnitz, Germany
Hospital Alemão Oswaldo Cruz
🇧🇷São Paulo, Brazil
Universidade Federal de São Paulo - Escola Paulista de Medicina
🇧🇷São Paulo, Brazil
Medica Superspecialty Hospital
🇮🇳Kolkata, West Bengal, India
Hospital PUC-CAMPINAS
🇧🇷Campinas, São Paulo, Brazil
CEMEC - Centro Multidisciplinar de Estudos Clinicos EPP Ltda
🇧🇷São Bernardo do Campo, São Paulo, Brazil
Pesquisare
🇧🇷Santo Andre, Sao Paulo, Brazil
First Moscow State Medical University n.a. Sechenov
🇷🇺Moscow, Russian Federation
Aakash Healthcare Super Speciality Hospital
🇮🇳New Delhi, India
Universitätsklinikum Schleswig-Holstein
🇩🇪Kiel, Schleswig-Holstein, Germany
Korea University Ansan Hospital
🇰🇷Ansan-si, Gyeonggi-do, Korea, Republic of
Hospital Santa Paula
🇧🇷São Paulo, Brazil
Klinikum Rechts der Isar der TU München
🇩🇪München, Bayern, Germany
Casa de Saude Santa Marcelina - Centro de Pesquisa Clinica
🇧🇷São Paulo, Brazil
Unity Hospital
🇮🇳Surat, Gujarat, India
Ospedale Niguarda Ca Granda
🇮🇹Milano, Italy
Nuovo Ospedale di Prato S. Stefano
🇮🇹Prato, Italy
Yokohama Municipal Citizen's Hospital
🇯🇵Yokohama, Kanagawa, Japan
Instituto Nacional de Cancerologia
🇲🇽Mexico City, FD, Mexico
City Clinical Hospital #15 named after O.M. Filatov
🇷🇺Moscow, Russian Federation
St. George's University Hospitals NHS Foundation Trust
🇬🇧London, United Kingdom
The Royal Cornwall Hospital
🇬🇧Truro, Cornwall, United Kingdom
Hospital Universitario Quironsalud Madrid
🇪🇸Pozuelo de Alarcon, Madrid, Spain
Hospital Universitario Infanta Leonor-INTERNAL MED
🇪🇸Madrid, Spain
Barnet Hospital
🇬🇧Barnet, Herts, United Kingdom
Hospital Clinico San Carlos
🇪🇸Madrid, Spain
St Joseph's Hospital and Medical Center
🇺🇸Phoenix, Arizona, United States
San Francisco VA Medical Center
🇺🇸San Francisco, California, United States
Henry Ford Hospital
🇺🇸Detroit, Michigan, United States
Oregon Health and Science University
🇺🇸Portland, Oregon, United States
Ajou University Hospital
🇰🇷Suwon, Gyeonggi-do, Korea, Republic of
Hospital Clínico Universitario de Valencia
🇪🇸Valencia, Spain
Clinica Adventista Belgrano
🇦🇷Caba, Ciudad Autónoma De Buenos Aire, Argentina
Fundacion Sanatorio Guemes
🇦🇷Caba, Buenos Aires, Argentina
Medanta-The Medicity
🇮🇳Gurgaon, Haryana, India
Great Lakes Clinical Trials
🇺🇸Chicago, Illinois, United States
South Shore Hospital
🇺🇸Weymouth, Massachusetts, United States
Parkview Regional Medical Center
🇺🇸Fort Wayne, Indiana, United States
OSU Med Intl Med Houston Ctr
🇺🇸Tulsa, Oklahoma, United States
Temple Univ School of Med
🇺🇸Philadelphia, Pennsylvania, United States
ClÃ-nica Zabala
🇦🇷Ciudad de Buenos Aires, AR, Argentina
Sanatorio Sagrado Corazón
🇦🇷Ciudad de Buenos Aires, AR, Argentina
Hospital Z.G.A.D "Evita Pueblo"
🇦🇷Berazategui, Buenos Aires, Argentina
Sanatorio de la Trinidad Mitre
🇦🇷Caba, Buenos Aires, Argentina
Hospital Interzonal General de Agudos "Eva Peron"
🇦🇷San Martin, Buenos Aires, Argentina
Clinica Viedma
🇦🇷Viedma, Río Negro, Argentina
Casa Hospital San Juan de Dios
🇦🇷Ramos Mejía, Buenos Aires, Argentina
Clinica Central S.A.
🇦🇷Villa Regina, Rio Negro, Argentina
Hospital San Roque
🇦🇷Cordoba, Argentina
Centro Hospitalar de Reabilitacao Ana Carolina Moura Xavier
🇧🇷Curitiba, Parana, Brazil
Hospital de Clinicas de Porto Alegre
🇧🇷Porto Alegre, RS, Brazil
Upeclin - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - UNESP
🇧🇷Botucatu, São Paulo, Brazil
Praxis Pesquisa Medica
🇧🇷Santo André, Sao Paulo, Brazil
CECIP - Centro de Estudos do Interior Paulista
🇧🇷Jaú, São Paulo, Brazil
Instituto Nacional de Cardiologia Ignacio Chavez
🇲🇽Mexico, DF, Mexico
Seoul National University Boramae Medical Center
🇰🇷Seoul, Seoul, Korea, Korea, Republic of
Instituto Nacional de Enfermedades Respiratorias
🇲🇽Mexico, DF, Mexico
Advanced Clinical Research, LLC
🇵🇷Bayamon, Puerto Rico
Hospital Txagorritxu
🇪🇸Vitoria, Alava, Spain
Saint-Petersburg City Pokrovskaya Hospital
🇷🇺Saint-Petersburg, Russian Federation
IPECC - Instituto de Pesquisa Clinica de Campinas
🇧🇷Campinas, São Paulo, Brazil
Seoul Medical Center
🇰🇷Seoul, Korea, Republic of