COV-BARRIER: A Study of Baricitinib (LY3009104) in Participants With COVID-19

• Sponsor: Eli Lilly and Company (Industry)
• Overall Status: Completed
• CT.gov ID: NCT04421027
• Collaborator: (none)
• Enrollment: 1,525
• Locations: 96
• Arms: 2
• Actual Duration (Months): 11.9
• Patients Per Site: 15.9
• Patients Per Site Per Month: 1.3

Study Details

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.

Condition or Disease	Intervention/Treatment	Phase
COVID-19	Drug: Baricitinib; Drug: Placebo	Phase 3

Study Design

• Study Type: Interventional
• 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: Jun 12, 2020
• Actual Primary Completion Date: Feb 12, 2021
• Actual Study Completion Date: Jun 10, 2021

Arms and Interventions

Arm	Intervention/Treatment
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.	Drug: Baricitinib; Given orally; Other Names: LY3009104
Placebo Comparator: Placebo + SOC Placebo (given as two placebo tablets) administered orally QD with standard of care.	Drug: Placebo; Given orally

Outcome Measures

Primary Outcome Measures

1. 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).

2. 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

1. 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.

2. Number of Ventilator-Free Days [Day 1 to Day 28]

   Number of days free of invasive mechanical ventilation.

3. 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.)

4. 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.

5. 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.

6. 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.

7. 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.

8. Duration of Hospitalization [Days 1 to Day 28]

   Duration of hospitalization.

9. 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.

10. Overall Mortality [Day 1 to Day 28]

    Number of deaths by Day 28.

11. Duration of Stay in the Intensive Care Unit (ICU) in Days [Day 1 to Day 28]

    Duration of stay in the ICU in days.

12. 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.

13. 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).

14. 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.

15. 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.

16. 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.

17. Time to Independence From Oxygen Therapy in Days [Day 1 to Day 28]

    Time to independence from oxygen therapy in days.

18. Number of Days With Supplemental Oxygen Use [Day 1 to Day 28]

    Number of days with supplemental oxygen use.

19. 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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Hospitalized with coronavirus (SARS-CoV-2) infection, confirmed by polymerase chain reaction (PCR) test or other commercial or public health assay in any specimen, as documented by either of the following:

• PCR positive in sample collected <72 hours prior to randomization; OR

• PCR positive in sample collected ≥72 hours prior to randomization (but no more than 14 days prior to randomization), documented inability to obtain a repeat sample (for example, due to lack of testing supplies, limited testing capacity, results taking >24 hours, etc.) AND progressive disease suggestive of ongoing SARS-CoV-2 infection.

• Requires supplemental oxygen at the time of study entry and at randomization.

• Have indicators of risk of progression: at least 1 inflammatory markers >upper limit of normal (ULN) (C reactive protein [CRP], D dimer, lactate dehydrogenase [LDH], ferritin) with at least 1 instance of elevation >ULN within 2 days before study entry.

Exclusion Criteria:

• Are receiving cytotoxic or biologic treatments (such as tumor necrosis factor [TNF] inhibitors, anti-interleukin-1 [IL-1], anti-IL-6 [tocilizumab or sarilumab], T-cell or B-cell targeted therapies (rituximab), interferon, or Janus kinase (JAK) inhibitors for any indication at study entry. Note: A washout period 4 weeks (or 5 half-lives, whichever is longer) is required prior to screening.

• Have ever received convalescent plasma or intravenous immunoglobulin [IVIg]) for COVID-19.

• Have received high dose corticosteroids at doses >20 mg per day (or prednisone equivalent) administered for ≥14 consecutive days in the month prior to study entry.

• Strong inhibitors of OAT3 (such as probenecid) that cannot be discontinued at study entry.

• Have received neutralizing antibodies, such as bamlanivimab, casirivimab and imdevimab for COVID-19.

• Have diagnosis of current active tuberculosis (TB) or, if known, latent TB treated for less than 4 weeks with appropriate anti-tuberculosis therapy per local guidelines (by history only, no screening tests required).

• Suspected serious, active bacterial, fungal, viral, or other infection (besides COVID-19) that in the opinion of the investigator could constitute a risk when taking investigational product.

• Have received any live vaccine within 4 weeks before screening, or intend to receive a live vaccine during the study. Note: Use of nonlive (inactivated) vaccinations is allowed for all participants.

• Require invasive mechanical ventilation, including extracorporeal membrane oxygenation (ECMO) at study entry.

• Current diagnosis of active malignancy that, in the opinion of the investigator, could constitute a risk when taking investigational product.

• Have a history of venous thromboembolism (VTE) (deep vein thrombosis [DVT] and/or pulmonary embolism [PE]) within 12 weeks prior to randomization or have a history of recurrent (>1) VTE (DVT/PE).

• Anticipated discharge from the hospital, or transfer to another hospital (or another unit), which is not a study site within 72 hours after study entry.

• Have neutropenia (absolute neutrophil count <1000 cells/microliters).

• Have lymphopenia (absolute lymphocyte count <200 cells/microliters).

• Have alanine aminotransferase (ALT) or aspartate aminotransferase (AST) >5 times ULN.

• Estimated glomerular filtration rate (eGFR) (Modification of Diet in Renal Disease [MDRD]) <30 milliliter/minute/1.73 meters squared.

• Have a known hypersensitivity to baricitinib or any of its excipients.

• Are currently enrolled in any other clinical study involving an investigation product or any other type of medical research judged not to be scientifically or medically compatible with this study. Note: The participant should not be enrolled (started) in another clinical trial for the treatment of COVID-19 or SARS CoV-2 through Day 28.

• Are pregnant, or intend to become pregnant or breastfeed during the study.

• Are using or will use extracorporeal blood purification (EBP) device to remove proinflammatory cytokines from the blood such as a cytokine absorption or filtering device, for example, CytoSorb®.

• Are, in the opinion of the investigator, unlikely to survive for at least 48 hours after screening.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Dignity Health Mercy Gilbert Medical Center	Gilbert	Arizona	United States	85297
2	Valleywise Health	Phoenix	Arizona	United States	85008
3	St Joseph's Hospital and Medical Center	Phoenix	Arizona	United States	85013
4	Hoag Memorial Hospital Presbyterian	Newport Beach	California	United States	92663
5	Sharp Memorial Hospital	San Diego	California	United States	92123
6	San Francisco VA Medical Center	San Francisco	California	United States	94121
7	Torrance Memorial Medical Center	Torrance	California	United States	90505
8	Holy Cross Hospital Inc.	Fort Lauderdale	Florida	United States	33308
9	Westchester General Hospital	Miami	Florida	United States	33155
10	Grady Health System	Atlanta	Georgia	United States	30303
11	Atlanta VA Medical Center	Decatur	Georgia	United States	30033
12	Great Lakes Clinical Trials	Chicago	Illinois	United States	60640
13	Parkview Regional Medical Center	Fort Wayne	Indiana	United States	46845
14	Community Hospital South	Indianapolis	Indiana	United States	46227
15	Franciscan St. Francis Health	Indianapolis	Indiana	United States	46237
16	South Shore Hospital	Weymouth	Massachusetts	United States	02190
17	Henry Ford Hospital	Detroit	Michigan	United States	48202
18	Renown Regional Med. Center	Reno	Nevada	United States	89502
19	SUNY Downstate	Brooklyn	New York	United States	11203
20	East Carolina University	Greenville	North Carolina	United States	27834
21	OSU Med Intl Med Houston Ctr	Tulsa	Oklahoma	United States	74127
22	Oregon Health and Science University	Portland	Oregon	United States	97239
23	Temple Univ School of Med	Philadelphia	Pennsylvania	United States	19140
24	Swedish Medical Center	Seattle	Washington	United States	98104
25	MultiCare Good Samaritan Hospital	Tacoma	Washington	United States	98405
26	Sanatorio Sagrado Corazón	Ciudad de Buenos Aires	AR	Argentina	C1039AAC
27	ClÃ-nica Zabala	Ciudad de Buenos Aires	AR	Argentina	C1426AAM
28	Hospital Z.G.A.D "Evita Pueblo"	Berazategui	Buenos Aires	Argentina	1884
29	Sanatorio de la Trinidad Mitre	Caba	Buenos Aires	Argentina	C1039AAO
30	Fundacion Sanatorio Guemes	Caba	Buenos Aires	Argentina	C1180AAX
31	Casa Hospital San Juan de Dios	Ramos Mejía	Buenos Aires	Argentina	1704
32	Hospital Interzonal General de Agudos "Eva Peron"	San Martin	Buenos Aires	Argentina	B1650 NBN
33	Clinica Adventista Belgrano	Caba	Ciudad Autónoma De Buenos Aire	Argentina	C1430EGF
34	Clinica Central S.A.	Villa Regina	Rio Negro	Argentina	R8336
35	Clinica Viedma	Viedma	Río Negro	Argentina	8500
36	Hospital San Roque	Cordoba		Argentina	5000
37	Hospital Felício Rocho	Belo Horizonte	Minas Gerais	Brazil	30110-934
38	Centro Hospitalar de Reabilitacao Ana Carolina Moura Xavier	Curitiba	Parana	Brazil	80035-090
39	CEPETI Centro de Ensino e Pesquisa em Terapia Intensiva	Curitiba	Paraná	Brazil	82530-200
40	CPCLIN	Natal	Rio Grande Do Norte	Brazil	59025-050
41	Hospital de Clinicas de Porto Alegre	Porto Alegre	RS	Brazil	90035-903
42	Hospital Carlos Fernando Malzoni Matao	Matao	Sao Paulo	Brazil	15990-060
43	Pesquisare	Santo Andre	Sao Paulo	Brazil	09080-110
44	Praxis Pesquisa Medica	Santo André	Sao Paulo	Brazil	09090-790
45	Faculdade de Medicina do ABC	Santo Andre	SP	Brazil	09060-870
46	Upeclin - Unidade de Pesquisa Clínica da Faculdade de Medicina de Botucatu - UNESP	Botucatu	São Paulo	Brazil	18618-687
47	IPECC - Instituto de Pesquisa Clinica de Campinas	Campinas	São Paulo	Brazil	13060-080
48	Hospital PUC-CAMPINAS	Campinas	São Paulo	Brazil	13060-904
49	CECIP - Centro de Estudos do Interior Paulista	Jaú	São Paulo	Brazil	17201-130
50	CEMEC - Centro Multidisciplinar de Estudos Clinicos EPP Ltda	São Bernardo do Campo	São Paulo	Brazil	09715-090
51	Real e Benemerita Associação Portuguesa de Beneficiencia	São Paulo		Brazil	01323-900
52	Hospital Alemão Oswaldo Cruz	São Paulo		Brazil	01327-001
53	Universidade Federal de São Paulo - Escola Paulista de Medicina	São Paulo		Brazil	04037-002
54	Hospital Santa Paula	São Paulo		Brazil	04556-100
55	Casa de Saude Santa Marcelina - Centro de Pesquisa Clinica	São Paulo		Brazil	08270-120
56	Universitätsklinikum Erlangen	Erlangen	Bayern	Germany	91054
57	Klinikum Rechts der Isar der TU München	München	Bayern	Germany	81675
58	Universitätsklinikum Schleswig-Holstein	Kiel	Schleswig-Holstein	Germany	24105
59	Klinikum Chemnitz gGmbH	Chemnitz		Germany	09116
60	Sir Ganga Ram Hospital	New Delhi	Delhi	India	110060
61	Unity Hospital	Surat	Gujarat	India	395010
62	Medanta-The Medicity	Gurgaon	Haryana	India	122001
63	Government Medical College (GMC) Aurangabad	Aurangabad	Maharashtra	India	431001
64	Government Medical College	Nagpur	Maharashtra	India	440003
65	Ruby Hall Clinic and Grant Medical Foundation	Pune	Maharashtra	India	411001
66	Medica Superspecialty Hospital	Kolkata	West Bengal	India	700099
67	Aakash Healthcare Super Speciality Hospital	New Delhi		India	110075
68	INMI Lazzaro Spallanzani	Roma	Rome	Italy	00149
69	Ospedale Niguarda Ca Granda	Milano		Italy	20162
70	Nuovo Ospedale di Prato S. Stefano	Prato		Italy	59100
71	Yokohama Municipal Citizen's Hospital	Yokohama	Kanagawa	Japan	2210855
72	Edogawa Medicare Hospital	Edagawa	Tokyo	Japan	133 0071
73	Tokyo Medical University Hachioji Medical Center	Hachioji	Tokyo	Japan	193-0998
74	Korea University Ansan Hospital	Ansan-si	Gyeonggi-do	Korea, Republic of	15355
75	Ajou University Hospital	Suwon	Gyeonggi-do	Korea, Republic of	16499
76	Seoul National University Boramae Medical Center	Seoul	Seoul, Korea	Korea, Republic of	07061
77	Seoul Medical Center	Seoul		Korea, Republic of	02053
78	Instituto Nacional de Cardiologia Ignacio Chavez	Mexico	DF	Mexico	14080
79	Instituto Nacional de Enfermedades Respiratorias	Mexico	DF	Mexico	14080
80	Instituto Nacional de Cancerologia	Mexico City	FD	Mexico	14080
81	Instituto Nacional de Ciencias Medicas y Nutrici Salva Zubir	Mexico City	Federal District	Mexico	14080
82	Hospital General Agustín O'Horán	Yucatan	Merida	Mexico	97000
83	ITESM Campus Monterrey	Monterrey	Nuevo Leon	Mexico	64710
84	Hospital Universitario "Dr. Jose Eleuterio Gonzalez"	Monterrey	Nuevo León	Mexico	64460
85	Advanced Clinical Research, LLC	Bayamon		Puerto Rico	00961
86	City Clinical Hospital #15 named after O.M. Filatov	Moscow		Russian Federation	111539
87	First Moscow State Medical University n.a. Sechenov	Moscow		Russian Federation	119991
88	Saint-Petersburg City Pokrovskaya Hospital	Saint-Petersburg		Russian Federation	199106
89	Hospital Txagorritxu	Vitoria	Alava	Spain	01009
90	Hospital Universitario Quironsalud Madrid	Pozuelo de Alarcon	Madrid	Spain	28223
91	Hospital Universitario Infanta Leonor-INTERNAL MED	Madrid		Spain	28031
92	Hospital Clinico San Carlos	Madrid		Spain	28040
93	Hospital Clínico Universitario de Valencia	Valencia		Spain	46010
94	The Royal Cornwall Hospital	Truro	Cornwall	United Kingdom	TR1 3LJ
95	Barnet Hospital	Barnet	Herts	United Kingdom	EN5 3DJ
96	St. George's University Hospitals NHS Foundation Trust	London		United Kingdom	SW17 0QT

Sponsors and Collaborators

• Eli Lilly and Company

Investigators

• 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

Study Documents (Full-Text)

• Study Protocol - Nov 25, 2020
• Statistical Analysis Plan - Mar 19, 2021

More Information

Additional Information:

• A Study of Baricitinib (LY3009104) in Participants With COVID-19 (COV-BARRIER)

Publications

None provided.

• Responsible Party: Eli Lilly and Company
• ClinicalTrials.gov Identifier: NCT04421027
• Other Study ID Numbers: 17830; I4V-MC-KHAA; 2020-001517-21
• First Posted: Jun 9, 2020
• Last Update Posted: Jul 28, 2022
• Last Verified: Jul 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Keywords provided by Eli Lilly and Company: coronavirus; coronavirus infection; safety
• Additional relevant MeSH terms: COVID-19

Study Results

Participant Flow

Arm/Group Title	Placebo + Standard of Care (SOC)	Baricitinib + SOC	Placebo + SOC Follow-Up	Baricitinib + SOC Follow-Up
Arm/Group Description	Placebo tablets administered orally every day (QD) with standard of care.	4 milligrams (mg) baricitinib administered orally QD with standard of care.	Participants did not receive drug during the Follow-Up Period.	Participants did not receive drug during the Follow-Up Period.
Period Title: Treatment Period
STARTED	761	764	0	0
Received at Least One Dose of Study Drug	752	750	0	0
COMPLETED	604	644	0	0
NOT COMPLETED	157	120	0	0
Period Title: Treatment Period
STARTED	0	0	613	645
COMPLETED	0	0	588	615
NOT COMPLETED	0	0	25	30

Baseline Characteristics

Arm/Group Title	Placebo +SOC	Baricitinib + SOC	Total
Arm/Group Description	Placebo administered orally QD with standard of care.	4 mg baricitinib administered orally QD with standard of care.	Total of all reporting groups
Overall Participants	761	764	1525
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	57.5 (13.8)	57.8 (14.3)	57.6 (14.1)
Sex: Female, Male (Count of Participants)
Female	288 37.8%	274 35.9%	562 36.9%
Male	473 62.2%	490 64.1%	963 63.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	168 22.1%	148 19.4%	316 20.7%
Asian	94 12.4%	80 10.5%	174 11.4%
Native Hawaiian or Other Pacific Islander	2 0.3%	3 0.4%	5 0.3%
Black or African American	36 4.7%	39 5.1%	75 4.9%
White	440 57.8%	480 62.8%	920 60.3%
More than one race	1 0.1%	2 0.3%	3 0.2%
Unknown or Not Reported	20 2.6%	12 1.6%	32 2.1%
Region of Enrollment (Count of Participants)
Puerto Rico	3 0.4%	8 1%	11 0.7%
Argentina	101 13.3%	107 14%	208 13.6%
United States	155 20.4%	154 20.2%	309 20.3%
Japan	19 2.5%	19 2.5%	38 2.5%
United Kingdom	7 0.9%	4 0.5%	11 0.7%
India	31 4.1%	19 2.5%	50 3.3%
Russia	54 7.1%	58 7.6%	112 7.3%
Spain	42 5.5%	45 5.9%	87 5.7%
South Korea	20 2.6%	16 2.1%	36 2.4%
Brazil	165 21.7%	172 22.5%	337 22.1%
Mexico	143 18.8%	138 18.1%	281 18.4%
Italy	10 1.3%	15 2%	25 1.6%
Germany	11 1.4%	9 1.2%	20 1.3%

Outcome Measures

1. Primary Outcome

Title	Percentage of Participants Who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (Including Extracorporeal Membrane Oxygenation [ECMO])
Description	Percentage of participants who die or require non-invasive ventilation/high-flow oxygen or invasive mechanical ventilation (including ECMO).
Time Frame	Day 1 to Day 28

Outcome Measure Data

Analysis Population Description

All participants randomly assigned to study intervention. Participants with missing baseline ordinal scale values were excluded.

Arm/Group Title	Placebo + SOC	Baricitinib + SOC
Arm/Group Description	Placebo administered orally QD with standard of care.	4 mg baricitinib administered orally QD with standard of care.
Measure Participants	756	762
Number (95% Confidence Interval) [percentage of participants]	30.5 4%	27.8 3.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1800
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.85
	Confidence Interval	(2-Sided) 95%; 0.67 to 1.08
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Percentage of Participants Who Die or Require Non-Invasive Ventilation/High-Flow Oxygen or Invasive Mechanical Ventilation (Including Extracorporeal Membrane Oxygenation [ECMO] Population 2
Description	Percentage of participants who die or require non-invasive ventilation or invasive mechanical ventilation, including ECMO.
Time Frame	Day 1 to Day 28

Outcome Measure Data

Analysis Population Description

All participants randomly assigned to study intervention who at baseline required oxygen supplementation and did not receive dexamethasone, or other systemic corticosteroids for the primary study condition.

Arm/Group Title	Placebo + SOC	Baricitinib + SOC
Arm/Group Description	Placebo administered orally QD with standard of care.	4 mg baricitinib administered orally QD with standard of care.
Measure Participants	109	96
Number (95% Confidence Interval) [percentage of participants]	27.1 3.6%	28.9 3.8%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7280
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.12
	Confidence Interval	(2-Sided) 95%; 0.58 to 2.16
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Secondary Outcome

Title	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
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.
Time Frame	Day 10

Outcome Measure Data

Analysis Population Description

All participants randomly assigned to study intervention. Participants with missing baseline ordinal scale values were excluded.

Arm/Group Title	Placebo + SOC	Baricitinib + SOC
Arm/Group Description	Placebo administered orally QD with standard of care.	4 mg baricitinib administered orally QD with standard of care.
Measure Participants	756	762
Number (95% Confidence Interval) [percentage of participants]	63.5 8.3%	65.0 8.5%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.5444
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.07
	Confidence Interval	(2-Sided) 95%; 0.86 to 1.34
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Number of Ventilator-Free Days
Description	Number of days free of invasive mechanical ventilation.
Time Frame	Day 1 to Day 28

Outcome Measure Data

Analysis Population Description

All participants randomly assigned to study intervention. Participants with missing baseline ordinal scale values were excluded.

Arm/Group Title	Placebo + SOC	Baricitinib + SOC
Arm/Group Description	Placebo administered orally QD with standard of care.	4 mg baricitinib administered orally QD with standard of care.
Measure Participants	756	762
Least Squares Mean (Standard Error) [days]	23.7 (0.39)	24.5 (0.39)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0586
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean difference (net)
	Estimated Value	0.75
	Confidence Interval	(2-Sided) 95%; -0.0 to 1.5
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.399
	Estimation Comments

5. Secondary Outcome

Title	Time to Recovery
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.)
Time Frame	Day 1 to Day 28

Outcome Measure Data

Analysis Population Description

All participants randomly assigned to study intervention.

Arm/Group Title	Placebo + SOC	Baricitinib + SOC
Arm/Group Description	Placebo administered orally QD with standard of care.	4 mg baricitinib administered orally QD with standard of care.
Measure Participants	761	764
Median (95% Confidence Interval) [days]	11.0	10.0

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1453
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.11
	Confidence Interval	(2-Sided) 95%; 0.99 to 1.24
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at 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.
Time Frame	Day 4

Outcome Measure Data

Analysis Population Description

All participants randomly assigned to study intervention. Participants with missing baseline ordinal scale were excluded.

Arm/Group Title	Placebo + SOC	Baricitinib + SOC
Arm/Group Description	Placebo administered orally QD with standard of care.	4 mg baricitinib administered orally QD with standard of care.
Measure Participants	756	762
Day 4 NIAID-OS 1	4.6 0.6%	5.2 0.7%
Day 4 NIAID-OS 2	1.5 0.2%	1.5 0.2%
Day 4 NIAID-OS 3	0.8 0.1%	0.3 0%
Day 4 NIAID-OS 4	19.4 2.5%	23.6 3.1%
Day 4 NIAID-OS 5	41.0 5.4%	39.0 5.1%
Day 4 NIAID-OS 6	22.4 2.9%	21.8 2.9%
Day 4 NIAID-OS 7	8.9 1.2%	8.1 1.1%
Day 4 NIAID-OS 8	1.4 0.2%	0.4 0.1%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments	Day 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0464
	Comments
	Method	Proportional Odds Model
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.21
	Confidence Interval	(2-Sided) 95%; 1.00 to 1.47
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at 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.
Time Frame	Day 7

Outcome Measure Data

Analysis Population Description

All participants randomly assigned to study intervention. Participants with missing baseline ordinal scale were excluded.

Arm/Group Title	Placebo + SOC	Baricitinib + SOC
Arm/Group Description	Placebo administered orally QD with standard of care.	4 mg baricitinib administered orally QD with standard of care.
Measure Participants	756	762
Day 7 NIAID-OS 1	20.2 2.7%	25.2 3.3%
Day 7 NIAID-OS 2	6.6 0.9%	5.8 0.8%
Day 7 NIAID-OS 3	0.5 0.1%	0.2 0%
Day 7 NIAID-OS 4	21.2 2.8%	20.6 2.7%
Day 7 NIAID-OS 5	22.5 3%	22.5 2.9%
Day 7 NIAID-OS 6	14.5 1.9%	13.8 1.8%
Day 7 NIAID-OS 7	11.2 1.5%	10.8 1.4%
Day 7 NIAID-OS 8	3.3 0.4%	1.2 0.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0172
	Comments
	Method	Proportional Odds Model
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.25
	Confidence Interval	(2-Sided) 95%; 1.04 to 1.49
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at 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.
Time Frame	Day 10

Outcome Measure Data

Analysis Population Description

All participants randomly assigned to study intervention. Participants with missing baseline ordinal scale were excluded.

Arm/Group Title	Placebo + SOC	Baricitinib + SOC
Arm/Group Description	Placebo administered orally QD with standard of care.	4 mg baricitinib administered orally QD with standard of care.
Measure Participants	756	762
Day 10 NIAID-OS 1	37.7 5%	40.4 5.3%
Day 10 NIAID-OS 2	9.4 1.2%	10.9 1.4%
Day 10 NIAID-OS 3	0.1 0%	0.1 0%
Day 10 NIAID-OS 4	16.2 2.1%	14.1 1.8%
Day 10 NIAID-OS 5	12.8 1.7%	12.4 1.6%
Day 10 NIAID-OS 6	8.1 1.1%	8.9 1.2%
Day 10 NIAID-OS 7	10.6 1.4%	10.4 1.4%
Day 10 NIAID-OS 8	5.1 0.7%	2.6 0.3%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0921
	Comments
	Method	Proportional Odds Model
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.17
	Confidence Interval	(2-Sided) 95%; 0.97 to 1.41
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Percentage of Participants at Each Clinical Status Using the National Institute of Allergy and Infectious Diseases Ordinal Scale (NIAID-OS) at Day 14
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.
Time Frame	Day 14

Outcome Measure Data

Analysis Population Description

All participants randomly assigned to study intervention. Participants with missing baseline ordinal scale were excluded.

Arm/Group Title	Placebo + SOC	Baricitinib + SOC
Arm/Group Description	Placebo administered orally QD with standard of care.	4 mg baricitinib administered orally QD with standard of care.
Measure Participants	756	762
Day 14 NIAID-OS 1	51.6 6.8%	56.3 7.4%
Day 14 NIAID-OS 2	11.2 1.5%	11.1 1.5%
Day 14 NIAID-OS 3	0.3 0%	0.1 0%
Day 14 NIAID-OS 4	8.0 1.1%	7.6 1%
Day 14 NIAID-OS 5	8.4 1.1%	7.3 1%
Day 14 NIAID-OS 6	3.6 0.5%	3.7 0.5%
Day 14 NIAID-OS 7	9.4 1.2%	8.9 1.2%
Day 14 NIAID-OS 8	7.5 1%	4.9 0.6%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0168
	Comments
	Method	Proportional Odds Model
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.28
	Confidence Interval	(2-Sided) 95%; 1.05 to 1.56
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Duration of Hospitalization
Description	Duration of hospitalization.
Time Frame	Days 1 to Day 28

Outcome Measure Data

Analysis Population Description

All participants randomly assigned to study intervention. Participants with missing baseline ordinal scale were excluded.

Arm/Group Title	Placebo + SOC	Baricitinib + SOC
Arm/Group Description	Placebo administered orally QD with standard of care.	4 mg baricitinib administered orally QD with standard of care.
Measure Participants	756	762
Least Squares Mean (Standard Error) [days]	13.7 (0.40)	12.9 (0.40)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0626
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Net)
	Estimated Value	-0.76
	Confidence Interval	(2-Sided) 95%; -1.6 to 0.0
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.408
	Estimation Comments

11. Secondary Outcome

Title	Percentage of Participants With a Change in Oxygen Saturation From < 94% to ≥ 94% From Baseline
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.
Time Frame	Day 10

Outcome Measure Data

Analysis Population Description

All participants randomly assigned to study intervention whose oxygen saturation (based on National Early Warning Score) is < 94% at baseline and have non-missing baseline and at least 1 postbaseline observation are in this population.

Arm/Group Title	Placebo + SOC	Baricitinib + SOC
Arm/Group Description	Placebo administered orally QD with standard of care.	4 mg baricitinib administered orally QD with standard of care.
Measure Participants	282	282
Number (95% Confidence Interval) [percentage of participants]	52.5 6.9%	56.7 7.4%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.4290
	Comments
	Method	Regression, Logistic
	Comments
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	1.15
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.63
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Overall Mortality
Description	Number of deaths by Day 28.
Time Frame	Day 1 to Day 28

Outcome Measure Data

Analysis Population Description

All participants randomly assigned to study intervention.

Arm/Group Title	Placebo + SOC	Baricitinib + SOC
Arm/Group Description	Placebo administered orally QD with standard of care.	4 mg baricitinib administered orally QD with standard of care.
Measure Participants	761	764
Number [event of death]	104	65

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0018
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.57
	Confidence Interval	(2-Sided) 95%; 0.41 to 0.78
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Duration of Stay in the Intensive Care Unit (ICU) in Days
Description	Duration of stay in the ICU in days.
Time Frame	Day 1 to Day 28

Outcome Measure Data

Analysis Population Description

All participants randomly assigned to study intervention with non-missing baseline NIAID OS and at least 1 postbaseline NIAID OS observation.

Arm/Group Title	Placebo + SOC	Baricitinib + SOC
Arm/Group Description	Placebo administered orally QD with standard of care.	4 mg baricitinib administered orally QD with standard of care.
Measure Participants	754	758
Least Squares Mean (Standard Error) [days]	3.17 (0.313)	3.19 (0.315)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.9526
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Net)
	Estimated Value	0.02
	Confidence Interval	(2-Sided) 95%; -0.62 to 0.65
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.323
	Estimation Comments

14. Secondary Outcome

Title	Time to Clinical Deterioration (One-category Increase on the NIAID-OS)
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.
Time Frame	Day 1 to Day 28

Outcome Measure Data

Analysis Population Description

All participants randomly assigned to study intervention. Participants with missing baseline ordinal scale values were excluded from analysis.

Arm/Group Title	Placebo + SOC	Baricitinib + SOC
Arm/Group Description	Placebo administered orally QD with standard of care.	4 mg baricitinib administered orally QD with standard of care.
Measure Participants	761	764
Median (95% Confidence Interval) [days]	NA	NA

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1831
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.887
	Confidence Interval	(2-Sided) 95%; 0.741 to 1.061
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Time to Resolution of Fever in Participants With Fever at Baseline
Description	Time to resolution of fever in participants with fever at baseline was calculated using cox proportional hazard regression model adjusted for baseline disease severity (OS 4, OS 5, OS 6), age (<65 years, >=65 years), region (United States, Europe, rest of world), and systemic corticosteroids used at baseline for primary study condition (Yes/No).
Time Frame	Day 1 to Day 28

Outcome Measure Data

Analysis Population Description

All participants randomly assigned to study intervention who had a fever at baseline.

Arm/Group Title	Placebo + SOC	Baricitinib + SOC
Arm/Group Description	Placebo administered orally QD with standard of care.	4 mg baricitinib administered orally QD with standard of care.
Measure Participants	354	357
Median (95% Confidence Interval) [days]	4.00	3.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.0243
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.202
	Confidence Interval	(2-Sided) 95%; 1.017 to 1.421
	Parameter Dispersion	Type: Value:
	Estimation Comments

16. Secondary Outcome

Title	Mean Change From Baseline on the National Early Warning Score (NEWS)
Description	The NEWS score is used to detect and report changes in illness severity in participants with acute illness to identify participants at risk for poor outcomes. The score is based on six physiological parameters (Respiration rate; oxygen saturation; temperature; systolic blood pressure; heart (pulse) rate, and level of consciousness). A score is assigned to each parameter, and the sum of the score represents the participant's risk of poor outcomes with a minimum score of 0 representing the better outcome, a score of 7 or greater reflects high clinical risk for worsening and maximum score of 19 representing the worse outcome.
Time Frame	Baseline, Day 4; Baseline, Day 7; Baseline, Day 10; Baseline, Day 14

Outcome Measure Data

Analysis Population Description

All participants randomly assigned to study intervention with baseline and 1 postbaseline observation.

Arm/Group Title	Placebo + SOC	Baricitinib + SOC
Arm/Group Description	Placebo administered orally QD with standard of care.	4 mg baricitinib administered orally QD with standard of care.
Measure Participants	636	647
Day 4	-0.59 (0.127)	-0.76 (0.125)
Day 7	-0.86 (0.145)	-1.04 (0.143)
Day 10	-1.33 (0.160)	-1.45 (0.158)
Day 14	-1.41 (0.183)	-1.66 (0.182)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments	Day 4
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.191
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 95%; -0.42 to 0.08
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.128
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments	Day 7
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.278
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	-0.17
	Confidence Interval	(2-Sided) 95%; -0.49 to 0.14
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.161
	Estimation Comments

Statistical Analysis 3

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments	Day 10
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.496
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	-0.13
	Confidence Interval	(2-Sided) 95%; -0.49 to 0.24
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.187
	Estimation Comments

Statistical Analysis 4

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments	Day 14
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.263
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Final Values)
	Estimated Value	-0.25
	Confidence Interval	(2-Sided) 95%; -0.70 to 0.19
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.226
	Estimation Comments

17. Secondary Outcome

Title	Time to Definitive Extubation
Description	Time to definitive extubation included participants who progressed to OS 7 at any time prior to Day 28.
Time Frame	Day 1 to Day 28

Outcome Measure Data

Analysis Population Description

All participants randomly assigned to study intervention who were intubated at some point during the study.

Arm/Group Title	Placebo + SOC	Baricitinib + SOC
Arm/Group Description	Placebo administered orally QD with standard of care.	4 mg baricitinib administered orally QD with standard of care.
Measure Participants	136	125
Median (95% Confidence Interval) [days]	NA	NA

18. Secondary Outcome

Title	Time to Independence From Non-Invasive Mechanical Ventilation
Description	Time to independence from non-invasive mechanical ventilation was measured in days among participants who required non-invasive ventilation.
Time Frame	Day 1 to Day 28

Outcome Measure Data

Analysis Population Description

All participants randomly assigned to study intervention whose baseline OS was 6 and were on non-invasive mechanical ventilation.

Arm/Group Title	Placebo + SOC	Baricitinib + SOC
Arm/Group Description	Placebo administered orally QD with standard of care.	4 mg baricitinib administered orally QD with standard of care.
Measure Participants	187	183
Median (95% Confidence Interval) [days]	11.00	12.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.6436
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.090
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

19. Secondary Outcome

Title	Time to Independence From Oxygen Therapy in Days
Description	Time to independence from oxygen therapy in days.
Time Frame	Day 1 to Day 28

Outcome Measure Data

Analysis Population Description

All randomized participants who had an ordinal scale score of 5 or 6 at baseline.

Arm/Group Title	Placebo + SOC	Baricitinib + SOC
Arm/Group Description	Placebo administered orally QD with standard of care.	4 mg baricitinib administered orally QD with standard of care.
Measure Participants	659	673
Median (95% Confidence Interval) [days]	8.00	8.00

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.1270
	Comments
	Method	Log Rank
	Comments
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.124
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

20. Secondary Outcome

Title	Number of Days With Supplemental Oxygen Use
Description	Number of days with supplemental oxygen use.
Time Frame	Day 1 to Day 28

Outcome Measure Data

Analysis Population Description

All participants randomly assigned to study intervention who have non-missing baseline and at least 1 postbaseline observation.

Arm/Group Title	Placebo + SOC	Baricitinib + SOC
Arm/Group Description	Placebo administered orally QD with standard of care.	4 mg baricitinib administered orally QD with standard of care.
Measure Participants	754	758
Least Squares Mean (Standard Error) [days]	4.60 (0.221)	4.37 (0.222)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.3058
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Net)
	Estimated Value	-0.23
	Confidence Interval	(2-Sided) 95%; -0.68 to 0.21
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.228
	Estimation Comments

21. Secondary Outcome

Title	Number of Days of Resting Respiratory Rate <24 Breaths Per Minute
Description	Number of days of resting respiratory rate <24 breaths per minute.
Time Frame	Day 1 to Day 28

Outcome Measure Data

Analysis Population Description

All participants randomly assigned to study intervention who had non-missing baseline and at least 1 postbaseline respiratory rate.

Arm/Group Title	Placebo + SOC	Baricitinib + SOC
Arm/Group Description	Placebo administered orally QD with standard of care.	4 mg baricitinib administered orally QD with standard of care.
Measure Participants	743	745
Least Squares Mean (Standard Error) [days]	9.62 (0.300)	9.73 (0.304)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Placebo + SOC, Baricitinib + SOC
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.7073
	Comments
	Method	ANOVA
	Comments
Method of Estimation	Estimation Parameter	LS Mean Difference (Net)
	Estimated Value	0.11
	Confidence Interval	(2-Sided) 95%; -0.49 to 0.72
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 0.306
	Estimation Comments

Adverse Events

Time Frame	Baseline up to 119 days Gender specific events occurring only in male or female participants have had the number of participants At Risk adjusted accordingly.
Adverse Event Reporting Description	All randomized participants who received at least 1 dose of study drug including participants who entered the post-treatment follow-up (f/u) period. The main study period included all events from the start of first dose to 28 days post dose. One participant receiving baricitinib had 2 events with fatal outcomes. One event occurred in the main study period and the second event occurred in the f/u period which resulted in the participant death being counted in both the main study and f/u periods.
Arm/Group Title	Placebo		4 Milligrams (mg) Baricitinib		Placebo Follow-up		4mg Baricitinib Follow-up
Arm/Group Description	Placebo tablets administered orally every day (QD) with standard of care.		4 milligrams (mg) baricitinib administered orally QD with standard of care.		Participants did not receive drug during the Follow-Up Period.		Participants did not receive drug during the Follow-Up Period.
All Cause Mortality
	Placebo		4 Milligrams (mg) Baricitinib		Placebo Follow-up		4mg Baricitinib Follow-up
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	104/752 (13.8%)		65/750 (8.7%)		16/613 (2.6%)		18/645 (2.8%)
Serious Adverse Events
	Placebo		4 Milligrams (mg) Baricitinib		Placebo Follow-up		4mg Baricitinib Follow-up
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	135/752 (18%)		110/750 (14.7%)		12/613 (2%)		18/645 (2.8%)
Blood and lymphatic system disorders
Anaemia	0/752 (0%)	0	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Disseminated intravascular coagulation	1/752 (0.1%)	1	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Lymphopenia	2/752 (0.3%)	2	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Thrombocytopenia	1/752 (0.1%)	1	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Cardiac disorders
Acute coronary syndrome	1/752 (0.1%)	1	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Acute myocardial infarction	1/752 (0.1%)	1	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Atrial fibrillation	1/752 (0.1%)	1	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Bradycardia	1/752 (0.1%)	1	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Cardiac arrest	3/752 (0.4%)	3	0/750 (0%)	0	1/613 (0.2%)	1	0/645 (0%)	0
Cardio-respiratory arrest	6/752 (0.8%)	6	3/750 (0.4%)	3	1/613 (0.2%)	1	1/645 (0.2%)	1
Cardiogenic shock	1/752 (0.1%)	1	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Cardiopulmonary failure	1/752 (0.1%)	1	2/750 (0.3%)	2	0/613 (0%)	0	0/645 (0%)	0
Coronary artery thrombosis	1/752 (0.1%)	1	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Myocardial infarction	0/752 (0%)	0	1/750 (0.1%)	1	1/613 (0.2%)	1	0/645 (0%)	0
Eye disorders
Diplopia	0/752 (0%)	0	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Gastrointestinal disorders
Acute abdomen	0/752 (0%)	0	0/750 (0%)	0	0/613 (0%)	0	1/645 (0.2%)	1
General disorders
Hypothermia	0/752 (0%)	0	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Multiple organ dysfunction syndrome	5/752 (0.7%)	5	4/750 (0.5%)	4	1/613 (0.2%)	1	1/645 (0.2%)	1
Infections and infestations
Bacteraemia	1/752 (0.1%)	1	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Bacterial infection	1/752 (0.1%)	1	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Covid-19	10/752 (1.3%)	10	8/750 (1.1%)	8	1/613 (0.2%)	1	1/645 (0.2%)	1
Covid-19 pneumonia	21/752 (2.8%)	21	21/750 (2.8%)	21	0/613 (0%)	0	0/645 (0%)	0
Device related bacteraemia	1/752 (0.1%)	1	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Empyema	0/752 (0%)	0	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Endocarditis staphylococcal	0/752 (0%)	0	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Enterobacter bacteraemia	0/752 (0%)	0	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Klebsiella bacteraemia	0/752 (0%)	0	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Klebsiella sepsis	0/752 (0%)	0	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Pneumonia	10/752 (1.3%)	10	8/750 (1.1%)	8	0/613 (0%)	0	1/645 (0.2%)	1
Pneumonia bacterial	3/752 (0.4%)	3	4/750 (0.5%)	5	0/613 (0%)	0	0/645 (0%)	0
Pneumonia staphylococcal	1/752 (0.1%)	1	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Pneumonia viral	2/752 (0.3%)	2	2/750 (0.3%)	2	0/613 (0%)	0	1/645 (0.2%)	1
Pulmonary sepsis	0/752 (0%)	0	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Sepsis	4/752 (0.5%)	4	3/750 (0.4%)	3	0/613 (0%)	0	0/645 (0%)	0
Septic shock	24/752 (3.2%)	24	13/750 (1.7%)	13	4/613 (0.7%)	4	5/645 (0.8%)	5
Severe acute respiratory syndrome	3/752 (0.4%)	3	1/750 (0.1%)	1	0/613 (0%)	0	1/645 (0.2%)	1
Staphylococcal bacteraemia	0/752 (0%)	0	2/750 (0.3%)	2	0/613 (0%)	0	0/645 (0%)	0
Staphylococcal infection	0/752 (0%)	0	2/750 (0.3%)	2	0/613 (0%)	0	0/645 (0%)	0
Staphylococcal sepsis	1/752 (0.1%)	1	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Systemic candida	0/752 (0%)	0	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Urinary tract infection	2/752 (0.3%)	2	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Investigations
Fibrin d dimer increased	0/752 (0%)	0	0/750 (0%)	0	0/613 (0%)	0	1/645 (0.2%)	1
Hepatic enzyme increased	1/752 (0.1%)	1	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Transaminases increased	0/752 (0%)	0	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Metabolism and nutrition disorders
Hyperglycaemia	0/752 (0%)	0	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Metabolic acidosis	1/752 (0.1%)	1	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Musculoskeletal and connective tissue disorders
Muscular weakness	0/752 (0%)	0	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Breast neoplasm	0/752 (0%)	0	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Nervous system disorders
Cerebral infarction	1/752 (0.1%)	1	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Cerebrovascular accident	1/752 (0.1%)	1	0/750 (0%)	0	0/613 (0%)	0	1/645 (0.2%)	1
Depressed level of consciousness	1/752 (0.1%)	1	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Guillain-barre syndrome	0/752 (0%)	0	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Haemorrhage intracranial	0/752 (0%)	0	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Ischaemic stroke	0/752 (0%)	0	2/750 (0.3%)	2	0/613 (0%)	0	0/645 (0%)	0
Neuralgia	1/752 (0.1%)	1	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Paresis	1/752 (0.1%)	1	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Subarachnoid haemorrhage	1/752 (0.1%)	1	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Renal and urinary disorders
Acute kidney injury	10/752 (1.3%)	10	7/750 (0.9%)	7	1/613 (0.2%)	1	0/645 (0%)	0
Renal failure	3/752 (0.4%)	3	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Renal impairment	1/752 (0.1%)	1	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Reproductive system and breast disorders
Acquired phimosis	0/473 (0%)	0	0/490 (0%)	0	1/377 (0.3%)	1	0/415 (0%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome	3/752 (0.4%)	3	2/750 (0.3%)	2	1/613 (0.2%)	1	1/645 (0.2%)	1
Acute respiratory failure	29/752 (3.9%)	29	17/750 (2.3%)	17	1/613 (0.2%)	1	2/645 (0.3%)	2
Dyspnoea	1/752 (0.1%)	1	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Pneumomediastinum	0/752 (0%)	0	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Pneumothorax	2/752 (0.3%)	2	6/750 (0.8%)	6	0/613 (0%)	0	0/645 (0%)	0
Pulmonary embolism	7/752 (0.9%)	7	12/750 (1.6%)	12	0/613 (0%)	0	0/645 (0%)	0
Respiratory distress	4/752 (0.5%)	4	3/750 (0.4%)	3	0/613 (0%)	0	0/645 (0%)	0
Respiratory failure	17/752 (2.3%)	17	10/750 (1.3%)	10	0/613 (0%)	0	1/645 (0.2%)	1
Surgical and medical procedures
Palliative care	1/752 (0.1%)	1	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Vascular disorders
Deep vein thrombosis	5/752 (0.7%)	5	4/750 (0.5%)	4	0/613 (0%)	0	0/645 (0%)	0
Dry gangrene	1/752 (0.1%)	1	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Embolism venous	0/752 (0%)	0	0/750 (0%)	0	0/613 (0%)	0	1/645 (0.2%)	1
Hypotension	1/752 (0.1%)	1	2/750 (0.3%)	2	0/613 (0%)	0	0/645 (0%)	0
Peripheral artery thrombosis	0/752 (0%)	0	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Peripheral embolism	0/752 (0%)	0	1/750 (0.1%)	1	0/613 (0%)	0	0/645 (0%)	0
Shock	0/752 (0%)	0	2/750 (0.3%)	2	0/613 (0%)	0	0/645 (0%)	0
Shock haemorrhagic	1/752 (0.1%)	1	0/750 (0%)	0	0/613 (0%)	0	0/645 (0%)	0
Other (Not Including Serious) Adverse Events
	Placebo		4 Milligrams (mg) Baricitinib		Placebo Follow-up		4mg Baricitinib Follow-up
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/752 (0%)		0/750 (0%)		0/613 (0%)		0/645 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is more than 60 days but less than or equal to 180 days. The sponsor cannot require changes to the communication and cannot extend the embargo.