eligibility Criteria: 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.
healthy Volunteers: false
minimum Age: 18 Years
sex: ALL
std Ages: ADULT
OLDER_ADULT

Treatment arms and interventions

arm Groups

description
4 milligrams (mg) of baricitinib (given as two 2 mg tablets) administered orally every day (QD) with standard of care.
intervention Names
Drug: Baricitinib
label
Baricitinib + Standard of Care (SOC)
type
EXPERIMENTAL
description
Placebo (given as two placebo tablets) administered orally QD with standard of care.
intervention Names
Drug: Placebo
label
Placebo + SOC
type
PLACEBO_COMPARATOR

interventions

arm Group Labels
Baricitinib + Standard of Care (SOC)
description
Given orally
name
Baricitinib
other Names
LY3009104
type
DRUG
arm Group Labels
Placebo + SOC
description
Given orally
name
Placebo
type
DRUG

Study design

allocation

RANDOMIZED

intervention Model

PARALLEL

masking Info

masking: DOUBLE
who Masked: PARTICIPANT
INVESTIGATOR

primary Purpose

TREATMENT

Enrollment

count: 1525
type: ACTUAL

Registered outcome plans (not posted results)

primary Outcomes

description
Percentage of participants who die or require non-invasive ventilation/high-flow oxygen or invasive mechanical ventilation (including ECMO).
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
description
Percentage of participants who die or require non-invasive ventilation or invasive mechanical ventilation, including ECMO.
measure
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

secondary Outcomes

description
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.
measure
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
description
Number of days free of invasive mechanical ventilation.
measure
Number of Ventilator-Free Days
time Frame
Day 1 to Day 28
description
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.)
measure
Time to Recovery
time Frame
Day 1 to Day 28
description
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.
measure
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
description
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.
measure
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
description
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.
measure
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
description
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.
measure
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
description
Duration of hospitalization.
measure
Duration of Hospitalization
time Frame
Days 1 to Day 28
description
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.
measure
Percentage of Participants With a Change in Oxygen Saturation From < 94% to ≥ 94% From Baseline
time Frame
Day 10
description
Number of deaths by Day 28.
measure
Overall Mortality
time Frame
Day 1 to Day 28
description
Duration of stay in the ICU in days.
measure
Duration of Stay in the Intensive Care Unit (ICU) in Days
time Frame
Day 1 to Day 28
description
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.
measure
Time to Clinical Deterioration (One-category Increase on the NIAID-OS)
time Frame
Day 1 to Day 28

Full study description

brief Summary: The reason for this study is to see if the study drug baricitinib is effective in hospitalized participants with COVID-19.

Source references

references

citation
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.
pmid
35695334
type
DERIVED
citation
Ely 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.
pmid
35123660
type
DERIVED
citation
Marconi 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.
pmid
34480861
type
DERIVED