Current best evidence for clinical care (more info)
BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), none have yet been shown to be efficacious.
METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults hospitalized with Covid-19 with evidence of lower respiratory tract involvement. Patients were randomly assigned to receive either remdesivir (200 mg loading dose on day 1, followed by 100 mg daily for up to 9 additional days) or placebo for up to 10 days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only.
RESULTS: A total of 1063 patients underwent randomization. The data and safety monitoring board recommended early unblinding of the results on the basis of findings from an analysis that showed shortened time to recovery in the remdesivir group. Preliminary results from the 1059 patients (538 assigned to remdesivir and 521 to placebo) with data available after randomization indicated that those who received remdesivir had a median recovery time of 11 days (95% confidence interval [CI], 9 to 12), as compared with 15 days (95% CI, 13 to 19) in those who received placebo (rate ratio for recovery, 1.32; 95% CI, 1.12 to 1.55; P<0.001). The Kaplan-Meier estimates of mortality by 14 days were 7.1% with remdesivir and 11.9% with placebo (hazard ratio for death, 0.70; 95% CI, 0.47 to 1.04). Serious adverse events were reported for 114 of the 541 patients in the remdesivir group who underwent randomization (21.1%) and 141 of the 522 patients in the placebo group who underwent randomization (27.0%).
CONCLUSIONS: Remdesivir was superior to placebo in shortening the time to recovery in adults hospitalized with Covid-19 and evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACCT-1 ClinicalTrials.gov number, NCT04280705.).
|Discipline / Specialty Area||Score|
|Family Medicine (FM)/General Practice (GP)||
|General Internal Medicine-Primary Care(US)||
A very good study. The criteria for severity of COVID-19 should be in the text not in the supplementary data.
Disappointing that a much-touted drug was not more useful. The likelihood of significant improvement, however, was not met. The conclusions were rather wishy-washy.
Important and timely results.
This study offers clinical proof-of-concept for remdesivir in COVID-19 disease. There is a lot of missing data on co-existing conditions that could conceivably impact on the study outcomes. The Kaplan-Meier Estimates of Cumulative Recoveries indicate that although overall data show a clear-cut benefit of remdesivir over placebo, those receiving either high-flow oxygen or non-invasive mechanical ventilation and those receiving mechanical ventilation or ECMO demonstrate a lack or loss of separation of curves with time. This suggests that the benefit of remdesivir on recovery time could be of less prominence with increasing severity of illness. A larger sample size in a future study should specifically address this issue. Given the overlapping confidence intervals in some of the preliminary subgroup analyses (Figure 3), the full analysis of the completed data set is eagerly awaited as are further results of larger clinical trials.
Extremely important. I hope the final results are more adequately powered for mortality.
Important study but a shame that the DSMB decided to stop the study prematurely as the difference in mortality was not significant. We might miss the chance and never get the true value of treatment on mortality.