BACKGROUND: Although several therapeutic agents have been evaluated for the treatment of coronavirus disease 2019 (Covid-19), no antiviral agents have yet been shown to be efficacious.
METHODS: We conducted a double-blind, randomized, placebo-controlled trial of intravenous remdesivir in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. 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 1062 patients underwent randomization (with 541 assigned to remdesivir and 521 to placebo). Those who received remdesivir had a median recovery time of 10 days (95% confidence interval [CI], 9 to 11), as compared with 15 days (95% CI, 13 to 18) among those who received placebo (rate ratio for recovery, 1.29; 95% CI, 1.12 to 1.49; P<0.001, by a log-rank test). In an analysis that used a proportional-odds model with an eight-category ordinal scale, the patients who received remdesivir were found to be more likely than those who received placebo to have clinical improvement at day 15 (odds ratio, 1.5; 95% CI, 1.2 to 1.9, after adjustment for actual disease severity). The Kaplan-Meier estimates of mortality were 6.7% with remdesivir and 11.9% with placebo by day 15 and 11.4% with remdesivir and 15.2% with placebo by day 29 (hazard ratio, 0.73; 95% CI, 0.52 to 1.03). Serious adverse events were reported in 131 of the 532 patients who received remdesivir (24.6%) and in 163 of the 516 patients who received placebo (31.6%).
CONCLUSIONS: Our data show that remdesivir was superior to placebo in shortening the time to recovery in adults who were hospitalized with Covid-19 and had evidence of lower respiratory tract infection. (Funded by the National Institute of Allergy and Infectious Diseases and others; ACTT-1 ClinicalTrials.gov number, NCT04280705.).
Bibliographical noteFunding Information:
The trial was sponsored and primarily funded by the NIAID, National Institutes of Health (NIH), Bethesda, MD. This trial has been funded in part with federal funds from the NIAID and the National Cancer Institute, NIH, under contract HHSN261200800001E 75N910D00024, task order number 75N91019F00130/75N91020F00010, and by the Department of Defense, Defense Health Program. This trial has been supported in part by the NIAID of the NIH under award numbers UM1AI148684, UM1AI148576, UM1AI148573, UM1AI148575, UM1AI148452, UM1AI148685, UM1AI148450, and UM1AI148689. The trial has also been funded in part by the governments of Denmark, Japan, Mexico, and Singapore. The trial site in South Korea received funding from the Seoul National University Hospital. Support for the London International Coordinating Centre was also provided by the United Kingdom Medical Research Council (MRC _UU_12023/23).
Dr. Chu reports receiving consulting fees from Merck and GlaxoSmithKline, grant support from Sanofi Pasteur, and research supplies from Cepheid, Ellume, and Genentech; Dr. Luetkemeyer, receiving grant support, paid to the University of California, San Francisco, from Gilead; Dr. Paredes, receiving grant support and advisory fees from Gilead Sciences, Merck Sharp and Dohme, and ViiV Healthcare; Dr. Touloumi, receiving grant support from Gilead Sciences Europe; Dr. Benfield, receiving grant support from Pfizer, Novo Nordisk Foundation, Simonsen Foundation, and Lundbeck Foundation, grant support and advisory board fees from GlaxoSmithKline, grant support and lecture fees from Pfizer, teaching fees from Boehringer Ingelheim, grant support and teaching fees from Gilead, and teaching fees and advisory board fees from Merck Sharp and Dohme; Dr. Fätkenheuer, receiving grant support, advisory board fees, and travel support from Gilead Sciences and Janssen and grant support and advisory board fees from Merck Sharp and Dohme and ViiV Healthcare; Dr. Kortepeter, receiving consulting fees and serving on a board for Integrum Scientific; Dr. Pett, receiving grant support from Gilead Sciences and ViiV Healthcare; and Dr. Osinusi, being employed by Gilead Sciences. No other potential conflict of interest relevant to this article was reported.
Copyright © 2020 Massachusetts Medical Society.
- Adenosine Monophosphate/administration & dosage
- Administration, Intravenous
- Alanine/administration & dosage
- Antiviral Agents/administration & dosage
- Coronavirus Infections/drug therapy
- Double-Blind Method
- Extracorporeal Membrane Oxygenation
- Kaplan-Meier Estimate
- Middle Aged
- Oxygen Inhalation Therapy
- Pneumonia, Viral/drug therapy
- Respiration, Artificial
- Time Factors
- Young Adult
PubMed: MeSH publication types
- Research Support, Non-U.S. Gov't
- Randomized Controlled Trial
- Clinical Trial, Phase III
- Journal Article
- Research Support, N.I.H., Extramural