In hospitalized patients with severe COVID-19, the antiviral drug remdesivir reduced recovery time by about one-third, a large, multinational trial has found. Preliminary results were published today in the New England Journal of Medicine.
Early results are being released after a review by independent experts overseeing the trial's safety and conduct determined that patients who received the drug were clearly benefiting. Remdesivir inhibits the virus's ability to replicate by interfering with its ability to make copies of its RNA genome.
"The main take-home messages are that remdesivir is effective in reducing the duration of illness in people who are hospitalized with COVID-19-but it's obviously not a cure-all. There was still a very high mortality in both groups. It gives us something to work with, but we will need other treatments on top of this antiviral to really improve outcomes," said Dr. Helen Chu, a study co-author and an assistant professor of allergy and infectious diseases at the University of Washington School of Medicine.
The trial is being conducted by the Adaptive COVID-19 Treatment Trial (ACTT-1) Study Group, a collaboration sponsored by U.S. National Institutes of Allergy and Infectious Diseases. The study included medical centers in North America, Europe and Asia.
To be enrolled in the study, the patients had to be hospitalized, have laboratory-confirmed COVID-19 infections, and evidence that the infection had reached their lungs.
In the study, 1,063 patients were randomly assigned to two groups: 541 were assigned to receive remdesivir daily for 10 days and 522 were assigned to receive a placebo. The study was blinded: Neither the clinicians nor the patients knew who was receiving the placebo or the active drug.
Participants comprised a relatively high-risk group of patients. Their average age was 58.9 years, and 64.3% were men. Most had at least one (27.9%) or two or more (52.1%) chronic conditions that have been linked to poorer outcomes with COVID-19, such as high blood pressure (49.6%), obesity (37.0%) and type 2 diabetes (20.7%).
The interim analysis found that patients who had received remdesivir had a median recovery time of 11 days, compared with 15 days for those on the placebo. A patient was considered to have recovered if they could be discharged from the hospital or remained in the hospital but required no further medical care-such as patients who could not return to nursing homes because of caution toward the disease.
The death rate was also less among those who received the drug (7.1%) than among those in the placebo group (11.9%), but the difference was not statistically significant. Serious events were slightly higher among those on placebo but, again, the difference was not statistically significant. The investigators reported no deaths related to the drug treatment.
Benefit was observed both in patients that had been sick for shorter and longer durations before receiving the drug. The greatest benefit was seen in patients with disease severe enough to require supplemental oxygen, but not so ill that they required a ventilator or extracorporeal membrane oxygenation, a treatment in which the patient's blood is circulated through an artificial lung to maintain adequate oxygen.
Dr. Anna Wald, a UW professor of medicine, epidemiology and laboratory medicine, said it is important be mindful that this is an interim analysis.
"We will soon have a more complete analysis of the data from all the patients, and when that is done we might see other benefits and be better able to define which groups of patients benefit the most."
It was a challenge to conduct a trial in the midst of a pandemic, when staff were busy caring for many very sick patients, Chu said. "In that setting, people want to focus on providing care to their patients; performing all the extra tasks required to conduct a trial is difficult. But the fact that all the staff-the phlebotomists, the nurses, the doctors and others-did this study under these conditions is a testament to the fact that we work at a place where research is given the highest priority."
The trial was primarily funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health (UM1AI148684, UM1AI148576, UM1AI148573, UM1AI148575, UM1AI148452, UM1AI148685, UM1AI148450, UM1AI148689, 3UM1AI148573-01S1), and by the U.S. Department of Defense. Support also came from the governments of Japan, Mexico, Denmark, and Singapore; the Seoul National University Hospital in Seoul, Republic of Korea; and UK Medical Research Council (MRC UU 12023/23).
