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- 1 Clinical Question
- 2 Bottom Line
- 3 Major Points
- 4 Guidelines
- 5 Design
- 6 Population
- 7 Interventions
- 8 Outcomes
- 9 Criticisms
- 10 Funding
- 11 Further Reading
Among patients hospitalized for Covid-19 with lower respiratory tract infection, does remdesivir plus baricitinib lower the time to recovery compared to remdesivir alone?
Baricitinib plus remdesivir lower recovery time and improves clinical status among Covid-19 patients hospitalized who require high-flow oxygen or noninvasive ventilation.
No guidelines have been published that reflect the results of this trial.
- International, multicenter, double-blind, placebo-controlled, randomized controlled trial
- N=1,033 patients with Covid-19
- Remdesivir plus Baricitinib (n=515)
- Remdesivir plus placeboStandard (n=518)
- Setting: 67 trial sites in 8 countries including Unites States (55), Singapore (4), South Korea (2), Mexico (2), Japan (1), Spain (1), the United Kingdom (1), and Denmark (1).
- Setting: 60 trial sites and 13 subsites in the United States, Denmark, the United Kingdom, Greece, Germany, Korea, Mexico, Spain, Japan, and Singapore
- Enrollment: 8 May 2020 to 19 July 2020
- Analysis: Intention-to-treat
- Primary outcome: Time to recovery
Eligibility criteria are included in the Supplemental Appendix.
- Age ≥18 years
- Laboratory-confirmed SARS-CoV-2 infection (as determined by a PCR)
- Evidence of lower respiratory tract infection at the time of enrollment based on one of the following:
- Radiographic infiltrates by imaging study
- SpO2 ≤94% on room air
- Requiring supplemental oxygen, mechanical ventilation, or ECMO
- No limit to the duration of symptoms prior to enrollment
- Not participating in another Covid-19 treatment clinical trial through Day 29
- Practicing heterosexual abstinence or using study-specified contraception through Day 29 for women of childbearing potential
- ALT or AST >5x ULN
- Impaired renal function by eGFR or need for hemodialysis or hemofiltration
- Allergy to study product
- Pregnancy or breast-feeding
- Anticipated discharge from the hospital or transfer to another hospital within 72 hours of enrollment
- Mean age: 55.4 years
- Male sex: 63.1%
- Number of co-existing conditions: none 15.6%, one 27.2%, two or more 57.2%
- Median time from symptom onset to randomization: 8 days
- Ordinal score of disease severity: (4) 13.7%, (5) 54.6%, (6) 20.9%, (7) 10.7%, (missing score) 0.1%
- 1:1 randomization to remdesivir plus baricitinib or remdesivir plus placebo
- Remdesivir: IV 200-mg loading dose on day 1, followed by IV 100 mg/d on days 2 through 10 or until hospital discharge or death
- Baricitinib: 4-mg/d (either PO or NG tube) for 14 days or until hospital discharge; 2-mg/d if eGFR < 60 mL/min
- Remdesivir+placebo: matching placebo administered according to the same schedule
Comparisons are remdesivir plus baricitinib vs. remdesivir plus placebo.
- Time to recovery
- 7 vs. 8 days (RR 1.16, 95% CI 1.01–1.32; P=0.03)
- Improvement in clinical status at day 15
- Odds ratio 1.3 (95% CI 1.4-3.6)
Subgroup analyses were conducted
- Serious adverse events
- 16.0% vs 21.0%
- Respiratory failure
- 3.7% vs 6.3%
- Grade 3-4 adverse events
- 40.7% vs. 46.8%
- National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH)
- Gilead Sciences, which is the manufacturer of remdesivir, provided the drug for use but did not provide any financial support.
- Eli Lilly, which is the manufacturer of baricitinib, provided the drug but did not provide any financial support.