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Remdesivir for COVID-19: Preliminary Report
Quick Takes
- Hospitalized adults with COVID-19 who received intravenous remdesivir had a shorter time to recovery compared to placebo.
- While mortality was numerically lower in the remdesivir group (7%) compared to placebo (12%), the difference was not statistically significant.
- Findings are preliminary, as a significant number of participants were still receiving treatment at the time of database freeze.
Study Questions:
Does treatment with intravenous remdesivir for 10 days in adults hospitalized with coronavirus disease 2019 (COVID-19) lead to a short recovery time compared to placebo?
Methods:
The ACTT-1 (Adaptive Covid-19 Treatment Trial) was an international double-blind, randomized, placebo-controlled trial involving 60 trial sites (of which 45 were in the United States), which randomized 1,063 adults in a 1:1 fashion to intravenous remdesivir (200 mg loading dose then 100 mg daily from day 2 to 10 or discharge/death if earlier) or placebo with the same administration schedule. Other off-label or experimental treatments for COVID-19 were prohibited after enrollment in the trial. The primary outcome measure was time to recovery, defined as reaching categories 1, 2, or 3 (discharged or hospitalized but no longer on oxygen supplementation) on an 8-category ordinal scale for disease severity. Secondary outcomes were mortality at 14 and 28 days after enrollment and grade 3-4 adverse events. The study was funded by the National Institute of Allergy and Infectious Diseases (NIAID).
Results:
A decision to release preliminary results early was made at the recommendation of the Data and Safety Monitoring Board after the number of recoveries exceeded the estimated target. At that time, 391 patients in the remdesivir group and 340 in the placebo group had completed the trial. The analysis, however, included all patients with post-baseline data (n = 1,059; 538 in the remdesivir arm and 521 in the placebo arm), regardless if they had completed the trial. Most patients were enrolled in North America (80%). The mean age of patients was 59 years, 64% were male, 53% were white, and 21% were black. Patients in the remdesivir group had a shorter time to recovery than patients in the placebo group (median of 11 days compared with 15 days; rate ratio for recovery of 1.32; p < 0.001). The difference persisted after adjusting for baseline score of disease severity. In prespecific subgroup analyses, there was no difference in time to recovery among patients on mechanical ventilation or extracorporeal membrane oxygenation (ECMO) (rate ratio for recovery of 0.95). While mortality was numerically lower in the remdesivir group compared to the placebo group (7% vs. 12%), the difference was not statistically significant (95% confidence interval, 0.47-1.04). There were no major differences in drug-related adverse events between both groups.
Conclusions:
Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with COVID-19.
Perspective:
Deriving conclusive findings in a trial in which participants were enrolled at different times during their disease course and received various other therapies is tremendously challenging. Despite its limitations, ACTT-1 provides encouraging findings, with a clear reduction in time to recovery with remdesivir and a trend toward lower mortality. The timing of initiation of treatment and the underlying clinical status appear to have an important impact on therapy-related outcomes and needs to be further investigated in larger studies. What is clear, however, is that remdesivir does not represent a panacea for COVID-19 and should certainly not be the reason for decreased vigilance with regard to efforts in curbing the virus’ spread.
Clinical Topics: COVID-19 Hub, Prevention
Keywords: Coronavirus, Coronavirus Infections, COVID-19, Extracorporeal Membrane Oxygenation, Off-Label Use, Patient Discharge, Primary Prevention, remdesivir, Respiration, Artificial, severe acute respiratory syndrome coronavirus 2
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