Remdesivir: Published Preliminary Results Show Shorter Recovery in COVID-19 Patients
The median recovery time in patients hospitalized with COVID-19 was 11 days with remdesivir, vs. 15 days with placebo, according to the preliminary results of the first stage of the Adaptive Covid-19 Treatment Trial (ACCT-1) trial published May 22 in the New England Journal of Medicine.
Led by the National Institute of Allergy and Infectious Diseases, and using an adaptive platform to rapidly conduct a series of phase 3 randomized, double-blind, placebo-controlled trials, the ACCT-1 trial enrolled patients at 60 trial sites and 13 subsites around the world between Feb. 21 and April 19, 2020.
Eighty percent of patients were enrolled at sites in the U.S. The top line results from ACCT-1 were released on April 29 through a press release after the data and safety monitoring board recommended unblinding the results.
John H. Beigel, MD, and colleagues randomized 1,063 adults hospitalized with COVID-19 with evidence of lower respiratory tract involvement to intravenous remdesivir (200 mg loading dose on day one, followed by 100 mg daily for up to nine additional days) or placebo for up to 10 days, or a matching placebo administered using the same schedule and volume as the active drug.
The mean age of patients was 58.9 years and 64% were men; 53.2% were white, 20.6% were black and 23.4% were Hispanic or Latino. Most patients had prespecified coexisting conditions: 50% had hypertension, 37% had obesity and 30% had type 2 diabetes.
The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection control purposes only.
The preliminary results showed a shorter median time to recovery in the 538 patients randomized to remdesivir compared with the 521 patients randomized to placebo (11 days vs. 15 days; 95 confidence interval [CI], 9-12 days vs. 13-19 days). The rate ratio for recovery was 1.32 (95% CI, 1.12-1.55; p<0.001).
Kaplan-Meier morality estimates by 14 days were lower with remdesivir vs. placebo (7.1% vs. 11.9%; hazard ratio for death, 0.70; 95% CI, 0.47-1.04).
The rate ratio for recovery was 1.47 (95% CI, 1.17-1.84) in patients with a baseline ordinal score of 5 (421 patients); 1.38 (95% CI, 0.94-2.03) in patients with a baseline score of 4 (127 patients; and 1.20 (95% CI, 0.79-1.81) for a baseline score of 6 (197 patients).
In patients on mechanical ventilation or ECMO at enrollment (baseline ordinal scores of 7; 272 patients), the rate ratio for recovery was 0.95 (95% CI, 0.64 to 1.42). A test of interaction of treatment with baseline score on the ordinal scale was not significant.
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%).
"These preliminary findings support the use of remdesivir for patients who are hospitalized with COVID-19 and require supplemental oxygen therapy," write the authors. They note an update of results will be provided after the full statistical analysis of the entire study population.
They add, "However, given high mortality despite the use of remdesivir, it is clear that treatment with an antiviral drug alone is not likely to be sufficient."
Future strategies should evaluate antiviral agents in combination with other therapeutic approaches or combinations of antiviral agents to continue to improve patient outcomes in COVID-19.
Keywords: COVID-19, Coronavirus, Coronavirus Infections, Diabetes Mellitus, Type 2, Patient Discharge, Clinical Trials Data Monitoring Committees, Clinical Trials Data Monitoring Committees, Antiviral Agents, Respiration, Artificial, National Institute of Allergy and Infectious Diseases (U.S.), Extracorporeal Membrane Oxygenation, Random Allocation, severe acute respiratory syndrome coronavirus 2, Hispanic Americans
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