COVID-19Phase 3COV-BARRIERNCT04421027
A Study of Baricitinib (LY3009104) in Participants With COVID-19
A Phase 3 study testing Baricitinib in people with COVID-19, run by Eli Lilly and Company at 96 sites in 13 countries.
Trial summary
The reason for this study is to see if the study drug baricitinib is effective in hospitalized participants with COVID-19. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- COVID-19
- What is being tested?
- Baricitinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,525 participants
- Where
- 96 sitesin 13 countries
- Study dates
- 12 Jun 2020to 10 Jun 2021
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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).
Show all 21Show fewer
- 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.
Trial locations and contacts
96 sites in 13 countries.
96 sites in 13 countries
United States25 sites
Grady Health System
Atlanta, Georgia, 30303
SUNY Downstate
Brooklyn, New York, 11203
Great Lakes Clinical Trials
Chicago, Illinois, 60640
Atlanta VA Medical Center
Decatur, Georgia, 30033
Henry Ford Hospital
Detroit, Michigan, 48202
Holy Cross Hospital Inc.
Fort Lauderdale, Florida, 33308
Parkview Regional Medical Center
Fort Wayne, Indiana, 46845
Dignity Health Mercy Gilbert Medical Center
Gilbert, Arizona, 85297
East Carolina University
Greenville, North Carolina, 27834
Community Hospital South
Indianapolis, Indiana, 46227
Franciscan St. Francis Health
Indianapolis, Indiana, 46237
Westchester General Hospital
Miami, Florida, 33155
Hoag Memorial Hospital Presbyterian
Newport Beach, California, 92663
Temple Univ School of Med
Philadelphia, Pennsylvania, 19140
Valleywise Health
Phoenix, Arizona, 85008
St Joseph's Hospital and Medical Center
Phoenix, Arizona, 85013
Oregon Health and Science University
Portland, Oregon, 97239
Renown Regional Med. Center
Reno, Nevada, 89502
Sharp Memorial Hospital
San Diego, California, 92123
San Francisco VA Medical Center
San Francisco, California, 94121
Swedish Medical Center
Seattle, Washington, 98104
MultiCare Good Samaritan Hospital
Tacoma, Washington, 98405
Torrance Memorial Medical Center
Torrance, California, 90505
OSU Med Intl Med Houston Ctr
Tulsa, Oklahoma, 74127
South Shore Hospital
Weymouth, Massachusetts, 02190
Brazil19 sites
Hospital Felício Rocho
Belo Horizonte, Minas Gerais, 30110-934
Upeclin - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - UNESP
Botucatu, São Paulo, 18618-687
IPECC - Instituto de Pesquisa Clinica de Campinas
Campinas, São Paulo, 13060-080
Hospital PUC-CAMPINAS
Campinas, São Paulo, 13060-904
Centro Hospitalar de Reabilitacao Ana Carolina Moura Xavier
Curitiba, Paraná, 80035-090
CEPETI Centro de Ensino e Pesquisa em Terapia Intensiva
Curitiba, Paraná, 82530-200
CECIP - Centro de Estudos do Interior Paulista
Jaú, São Paulo, 17201-130
Hospital Carlos Fernando Malzoni Matao
Matão, São Paulo, 15990-060
CPCLIN
Natal, Rio Grande do Norte, 59025-050
Hospital de Clinicas de Porto Alegre
Porto Alegre, Rio Grande do Sul, 90035-903
Faculdade de Medicina do ABC
Santo André, São Paulo, 09060-870
Pesquisare
Santo André, São Paulo, 09080-110
Praxis Pesquisa Medica
Santo André, São Paulo, 09090-790
CEMEC - Centro Multidisciplinar de Estudos Clinicos EPP Ltda
São Bernardo do Campo, São Paulo, 09715-090
Real e Benemerita Associação Portuguesa de Beneficiencia
São Paulo, 01323-900
Hospital Alemão Oswaldo Cruz
São Paulo, 01327-001
Universidade Federal de São Paulo - Escola Paulista de Medicina
São Paulo, 04037-002
Hospital Santa Paula
São Paulo, 04556-100
Casa de Saude Santa Marcelina - Centro de Pesquisa Clinica
São Paulo, 08270-120
Argentina11 sites
Hospital Z.G.A.D "Evita Pueblo"
Berazategui, Buenos Aires, 1884
Sanatorio de la Trinidad Mitre
CABA, Buenos Aires, C1039AAO
Fundacion Sanatorio Guemes
CABA, Buenos Aires, C1180AAX
Clinica Adventista Belgrano
CABA, Ciudad Autónoma de Buenos Aire, C1430EGF
Sanatorio Sagrado Corazón
Ciudad de Buenos Aires, AR, C1039AAC
ClÃ-nica Zabala
Ciudad de Buenos Aires, AR, C1426AAM
Hospital San Roque
Córdoba, 5000
Casa Hospital San Juan de Dios
Ramos Mejía, Buenos Aires, 1704
Hospital Interzonal General de Agudos "Eva Peron"
San Martín, Buenos Aires, B1650 NBN
Clinica Viedma
Viedma, Río Negro Province, 8500
Clinica Central S.A.
Villa Regina, Río Negro Province, R8336
India8 sites
Government Medical College (GMC) Aurangabad
Chhatrapati Sambhajinagar, Maharashtra, 431001
Medanta-The Medicity
Gurgaon, Haryana, 122001
Medica Superspecialty Hospital
Kolkata, West Bengal, 700099
Government Medical College
Nagpur, Maharashtra, 440003
Sir Ganga Ram Hospital
New Delhi, National Capital Territory of Delhi, 110060
Aakash Healthcare Super Speciality Hospital
New Delhi, 110075
Ruby Hall Clinic and Grant Medical Foundation
Pune, Maharashtra, 411001
Unity Hospital
Surat, Gujarat, 395010
Mexico7 sites
Instituto Nacional de Cancerologia
Mexico City, FD, 14080
Instituto Nacional de Ciencias Medicas y Nutrici Salva Zubir
Mexico City, Federal District, 14080
Instituto Nacional de Cardiologia Ignacio Chavez
Mexico City, Mexico City, 14080
Instituto Nacional de Enfermedades Respiratorias
Mexico City, Mexico City, 14080
Hospital Universitario "Dr. Jose Eleuterio Gonzalez"
Monterrey, Nuevo León, 64460
ITESM Campus Monterrey
Monterrey, Nuevo León, 64710
Hospital General Agustín O'Horán
Yucatán, Merida, 97000
Spain5 sites
Hospital Universitario Infanta Leonor-INTERNAL MED
Madrid, 28031
Hospital Clinico San Carlos
Madrid, 28040
Hospital Universitario Quironsalud Madrid
Pozuelo de Alarcón, Madrid, 28223
Hospital Clínico Universitario de Valencia
Valencia, 46010
Hospital Txagorritxu
Vitoria-Gasteiz, Alava, 01009
Germany4 sites
Klinikum Chemnitz gGmbH
Chemnitz, 09116
Universitätsklinikum Erlangen
Erlangen, Bavaria, 91054
Universitätsklinikum Schleswig-Holstein
Kiel, Schleswig-Holstein, 24105
Klinikum Rechts der Isar der TU München
München, Bavaria, 81675
South Korea4 sites
Korea University Ansan Hospital
Ansan-si, Gyeonggi-do, 15355
Seoul National University Boramae Medical Center
Seoul, Seoul, Korea, 07061
Seoul Medical Center
Seoul, 02053
Ajou University Hospital
Suwon, Gyeonggi-do, 16499
Italy3 sites
Ospedale Niguarda Ca Granda
Milan, 20162
Nuovo Ospedale di Prato S. Stefano
Prato, 59100
INMI Lazzaro Spallanzani
Roma, Rome, 00149
Japan3 sites
Edogawa Medicare Hospital
Edagawa, Tokyo, 133 0071
Tokyo Medical University Hachioji Medical Center
Hachiōji, Tokyo, 193-0998
Yokohama Municipal Citizen's Hospital
Yokohama, Kanagawa, 2210855
Russia3 sites
City Clinical Hospital #15 named after O.M. Filatov
Moscow, 111539
First Moscow State Medical University n.a. Sechenov
Moscow, 119991
Saint-Petersburg City Pokrovskaya Hospital
Saint Petersburg, 199106
United Kingdom3 sites
Barnet Hospital
Barnet, Herts, EN5 3DJ
St. George's University Hospitals NHS Foundation Trust
London, SW17 0QT
The Royal Cornwall Hospital
Truro, Cornwall, TR1 3LJ
About this study
Official title: A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase 3 Study of Baricitinib in Patients With COVID-19 Infection
The reason for this study is to see if the study drug baricitinib is effective in hospitalized participants with COVID-19.
- Conditions
- COVID-19
- Being tested
- Baricitinib, Placebo
- Keywords
- coronavirus, coronavirus infection, safety
- Medical subject headings
- COVID-19, Coronavirus Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
BaricitinibDrug
Also called LY3009104
Given orally
PlaceboDrug
Given orally
| Study group | Role | What they receive |
|---|---|---|
| Baricitinib + Standard of Care (SOC) | Experimental | 4 milligrams (mg) of baricitinib (given as two 2 mg tablets) administered orally every day (QD) with standard of care. Receives: Drug: Baricitinib |
| Placebo + SOC | Placebo comparator | Placebo (given as two placebo tablets) administered orally QD with standard of care. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: Day 1 to Day 28
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.
Measured: Day 1 to Day 28
Secondary outcomes (19)
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.
Measured: Day 10
Number of Ventilator-Free Days
Number of days free of invasive mechanical ventilation.
Measured: Day 1 to Day 28
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.)
Measured: Day 1 to Day 28
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:
- 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.
Measured: Day 4
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:
- 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.
Measured: Day 7
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:
- 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.
Measured: Day 10
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:
- 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.
Measured: Day 14
Duration of Hospitalization
Duration of hospitalization.
Measured: Days 1 to Day 28
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.
Measured: Day 10
Overall Mortality
Number of deaths by Day 28.
Measured: Day 1 to Day 28
Duration of Stay in the Intensive Care Unit (ICU) in Days
Duration of stay in the ICU in days.
Measured: Day 1 to Day 28
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.
Measured: Day 1 to Day 28
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).
Measured: Day 1 to Day 28
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.
Measured: Baseline, Day 4; Baseline, Day 7; Baseline, Day 10; Baseline, Day 14
Time to Definitive Extubation
Time to definitive extubation included participants who progressed to OS 7 at any time prior to Day 28.
Measured: Day 1 to Day 28
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.
Measured: Day 1 to Day 28
Time to Independence From Oxygen Therapy in Days
Time to independence from oxygen therapy in days.
Measured: Day 1 to Day 28
Number of Days With Supplemental Oxygen Use
Number of days with supplemental oxygen use.
Measured: Day 1 to Day 28
Number of Days of Resting Respiratory Rate <24 Breaths Per Minute
Number of days of resting respiratory rate <24 breaths per minute.
Measured: Day 1 to Day 28
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2020
- Study start12 Jun 2020
- Primary completion12 Feb 2021
- Study completion10 Jun 2021
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for COVID-19Studies of the same condition, open and under way.
- More trials run by Eli Lilly and CompanyThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 1,525 participants (actual)
Sponsor and investigators
- Lead sponsor
- Eli Lilly and Company
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Call 1-877-CTLILLY (1-877-265-4559 or 1-317-615-4559) Mon - Fri 9AM - 5PM Eastern Time (UTC/GMT - 5 hours, EST), Study director, Eli Lilly and Company
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04421027
- Sponsor's protocol ID
- 17830
- Other IDs
- I4V-MC-KHAA, 2020-001517-21
- Acronym
- COV-BARRIER
- Status last verified
- Jul 2022
- First submitted
- 5 Jun 2020
- Last updated
- 28 Jul 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: 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
Publications
Kramer A, Prinz C, Fichtner F, Fischer AL, Thieme V, Grundeis F, Spagl M, Seeber C, Piechotta V, Metzendorf MI, Golinski M, Moerer O, Stephani C, Mikolajewska A, Kluge S, Stegemann M, Laudi S, Skoetz N. Janus kinase inhibitors for the treatment of COVID-19. Cochrane Database Syst Rev. 2022 Jun 13;6(6):CD015209. doi: 10.1002/14651858.CD015209.
PubMed 35695334Ely EW, Ramanan AV, Kartman CE, de Bono S, Liao R, Piruzeli MLB, Goldman JD, Saraiva JFK, Chakladar S, Marconi VC; COV-BARRIER Study Group. Efficacy and safety of baricitinib plus standard of care for the treatment of critically ill hospitalised adults with COVID-19 on invasive mechanical ventilation or extracorporeal membrane oxygenation: an exploratory, randomised, placebo-controlled trial. Lancet Respir Med. 2022 Apr;10(4):327-336. doi: 10.1016/S2213-2600(22)00006-6. Epub 2022 Feb 3.
PubMed 35123660Marconi VC, Ramanan AV, de Bono S, Kartman CE, Krishnan V, Liao R, Piruzeli MLB, Goldman JD, Alatorre-Alexander J, de Cassia Pellegrini R, Estrada V, Som M, Cardoso A, Chakladar S, Crowe B, Reis P, Zhang X, Adams DH, Ely EW; COV-BARRIER Study Group. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Lancet Respir Med. 2021 Dec;9(12):1407-1418. doi: 10.1016/S2213-2600(21)00331-3. Epub 2021 Sep 1.
PubMed 34480861
Study at a glance
From the registry record, last updated by the sponsor on 28 Jul 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Phase 3 Study of Baricitinib in Patients With COVID-19 Infection
- ClinicalTrials.gov ID
- NCT04421027
- Acronym / sponsor ID
- COV-BARRIER / 17830
- Conditions
- COVID-19
- Keywords
- coronavirus, coronavirus infection, safety
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,525 participants (actual)
- Lead sponsor
- Eli Lilly and CompanyIndustry (pharma, biotech, devices)
- Study start
- 12 Jun 2020 (actual)
- Primary completion
- 12 Feb 2021 (actual)
- Study completion
- 10 Jun 2021 (actual)
- First posted
- 9 Jun 2020 (actual)
- Results
- Posted 24 Mar 2022
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The reason for this study is to see if the study drug baricitinib is effective in hospitalized participants with COVID-19.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Baricitinib + Standard of Care (SOC) | Experimental | Drug: Baricitinib4 milligrams (mg) of baricitinib (given as two 2 mg tablets) administered orally every day (QD) with standard of care. |
| Placebo + SOC | Placebo comparator | Drug: PlaceboPlacebo (given as two placebo tablets) administered orally QD with standard of care. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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:
- 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.
Key exclusion criteria (21 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| BaricitinibAlso: LY3009104Given orally | Drug | Baricitinib + Standard of Care (SOC) |
| PlaceboGiven orally | Drug | Placebo + SOC |
Primary outcome
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.
19 secondary outcomes
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
Number of Ventilator-Free Days
Time frame: Day 1 to Day 28
Time to Recovery
Time frame: Day 1 to Day 28
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
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
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
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
Duration of Hospitalization
Time frame: Days 1 to Day 28
Percentage of Participants With a Change in Oxygen Saturation From < 94% to ≥ 94% From Baseline
Time frame: Day 10
Overall Mortality
Time frame: Day 1 to Day 28
Duration of Stay in the Intensive Care Unit (ICU) in Days
Time frame: Day 1 to Day 28
Time to Clinical Deterioration (One-category Increase on the NIAID-OS)
Time frame: Day 1 to Day 28
Time to Resolution of Fever in Participants With Fever at Baseline
Time frame: Day 1 to Day 28
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
Time to Definitive Extubation
Time frame: Day 1 to Day 28
Time to Independence From Non-Invasive Mechanical Ventilation
Time frame: Day 1 to Day 28
Time to Independence From Oxygen Therapy in Days
Time frame: Day 1 to Day 28
Number of Days With Supplemental Oxygen Use
Time frame: Day 1 to Day 28
Number of Days of Resting Respiratory Rate <24 Breaths Per Minute
Time frame: Day 1 to Day 28
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Jul 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 35695334Kramer A, Prinz C, Fichtner F, Fischer AL, Thieme V, Grundeis F, Spagl M, Seeber C, Piechotta V, Metzendorf MI, Golinski M, Moerer O, Stephani C, Mikolajewska A, Kluge S, Stegemann M, Laudi S, Skoetz N. Janus kinase inhibitors for the treatment of COVID-19. Cochrane Database Syst Rev. 2022 Jun 13;6(6):CD015209. doi: 10.1002/14651858.CD015209.
- Derived from this study: PubMed 35123660Ely EW, Ramanan AV, Kartman CE, de Bono S, Liao R, Piruzeli MLB, Goldman JD, Saraiva JFK, Chakladar S, Marconi VC; COV-BARRIER Study Group. Efficacy and safety of baricitinib plus standard of care for the treatment of critically ill hospitalised adults with COVID-19 on invasive mechanical ventilation or extracorporeal membrane oxygenation: an exploratory, randomised, placebo-controlled trial. Lancet Respir Med. 2022 Apr;10(4):327-336. doi: 10.1016/S2213-2600(22)00006-6. Epub 2022 Feb 3.
- Derived from this study: PubMed 34480861Marconi VC, Ramanan AV, de Bono S, Kartman CE, Krishnan V, Liao R, Piruzeli MLB, Goldman JD, Alatorre-Alexander J, de Cassia Pellegrini R, Estrada V, Som M, Cardoso A, Chakladar S, Crowe B, Reis P, Zhang X, Adams DH, Ely EW; COV-BARRIER Study Group. Efficacy and safety of baricitinib for the treatment of hospitalised adults with COVID-19 (COV-BARRIER): a randomised, double-blind, parallel-group, placebo-controlled phase 3 trial. Lancet Respir Med. 2021 Dec;9(12):1407-1418. doi: 10.1016/S2213-2600(21)00331-3. Epub 2021 Sep 1.
- A Study of Baricitinib (LY3009104) in Participants With COVID-19 (COV-BARRIER)Link provided by the sponsor.
- Individual participant dataSharing planned: Yes. 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
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Call 1-877-CTLILLY (1-877-265-4559 or 1-317-615-4559) Mon - Fri 9AM - 5PM Eastern Time (UTC/GMT - 5 hours, EST) study director
Eli Lilly and Company
96 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Baricitinib in people with COVID-19, run by Eli Lilly and Company at 96 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 21 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 28 Jul 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 96 sites in United States, Brazil, Argentina, India, Mexico and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 24 Mar 2022). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04421027, which also lists 3 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Jul 2022.