[Summary text]
We have used version 2 of the Cochrane risk-of-bias tool for randomised trials (RoB 2) to assess the risk of bias in the trials included in this meta-analysis. In RoB 2, judgement[s] can be 'Low' or 'High' risk of bias, or can express 'Some concerns' for each of the domains assessed FOR EACH RESULT within a study, and for the overall risk-of-bias assessment for each study RESULT. The Risk of Bias tables in RevMan v5 use the domain judgements from version 1 of the Cochrane risk-of-bias tool: Low, High, Unclear. Therefore an Unclear judgement in the tables in this RevMan file equate[s] to a judgement of Some concerns for RoB 2.
Study design: Randomized controlled trial
Study grouping:
Baseline Characteristics
Baricitinib plus remdesivir
Remdesivir
Overall
Included criteria: 1. Admitted to a hospital with symptoms suggestive of COVID-19.2. Subject (or legally authorized representative) provides informed consent prior toinitiation of any study procedures.3. Subject (or legally authorized representative) understands and agrees to comply withplanned study procedures.4. Male or non-pregnant female adult ≥18 years of age at time of enrollment.5. Has laboratory-confirmed SARS-CoV-2 infection as determined by PCR or othercommercial or public health assay in any specimen6. Illness of any duration, and at least one of the following:• Radiographic infiltrates by imaging (chest x-ray, CT scan, etc.), OR• SpO2 ≤ 94% on room air, OR• Requiring supplemental oxygen, OR• Requiring mechanical ventilation.7. Women of childbearing potential must agree to either abstinence or use at least oneprimary form of contraception not including hormonal contraception from the time ofscreening through Day 29.8. Agrees to not participate in another clinical trial for the treatment of COVID-19 orSARS-CoV-2 through Day 29.
Excluded criteria: ALT or AST > 5 times the upper limit of normal.2. Estimated glomerular filtration rate (eGFR) < 30 ml/min (including patients receivinghemodialysis or hemofiltration).3. Pregnancy or breastfeeding.4. Anticipated discharge from the hospital or transfer to another hospital which is not astudy site within 72 hours.5. Allergy to any study medication.
Pretreatment:
Intervention Characteristics
Baricitinib plus remdesivir
Remdesivir
All-cause mortality (Day 28)
All-cause mortality (Day 14)
Invasive mechanical ventilation
NIV / HFNO
Serious adverse events
Adverse events
Clinical recovery
Sponsorship source: Division of Microbiology and Infectious Diseases (DMID),National Institute of Allergy and Infectious Diseases,National Institutes of Health
Country: United States of America
Setting: Hospital
Comments:
Authors name: A.C. Kalil
Institution: University of Nebraska Medical Center
Email: akalil@unmc.edu
Address: University of Nebraska MedicalCenter, 985400 Nebraska Medicine,Omaha, NE 68198-5400
Clinical trial identifier: ClinicalTrials.gov number,NCT04421027
Preprint or peer reviewed: Peer reviewed
Single centre or multi-centre (no. of centres): Multi-centre 67 trial sites in 8 countries:the United States (55 sites), Singapore (4),South Korea (2), Mexico (2), Japan (1), Spain (1),the United Kingdom (1), and Denmark (1).
Included
Median duration of initial hospitalization (IQR) — days Bricitinib 8 (5 to 15) vs placebo 8 (5 to 20)Median time to recovery (95% CI) — days Bricitinib 7 (6–8) vs placebo 8 (7–9)
Included
New use of Mechanical ventilation No. of patients/total no. Baricitinib+RDV 46/461 vs Placebo+RDV 70/461.
We have used version 2 of the Cochrane risk-of-bias tool for randomised trials (RoB 2) to assess the risk of bias for this study. Refer to Main text > Published notes for more details.
Selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence
Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment
Performance bias due to knowledge of the allocated interventions by participants and personnel during the study
Detection bias due to knowledge of the allocated interventions by outcome assessors
Attrition bias due to amount, nature or handling of incomplete outcome data
Reporting bias due to selective outcome reporting
Bias due to problems not covered elsewhere in the table
"Randomisation was stratified by study site and disease severity at enrollment and was performed using a web-based Internet Data Entry System, Advantage eClinical".
Allocation sequence concealed
Randomisation performed using a web-based internet data entry system, Advantage eClinical.
"The trial team was unaware of the trial-group assignments until after all data queries were resolved and the database was locked."
The majority of patients received intended intervention.
Results reported for intention to treat population.