Good news in the fight against SARS-CoV-2 was published in the New England Journal of Medicine on Friday. Remdesivir, an antiviral drug, originally developed as a potential treatment for Ebola, has been shown to shorten the recovery time of patients infected with coronavirus. At the end of April, the first results of this phase 3 clinical trial suggested that remdesivir could be useful in the treatment of patients with COVID-19 – this new document confirms this. It is not a cure, but the drug has shortened recovery time from an average of 15 days to 11 days.
The trial involved 1,059 COVID-19 patients at 60 different sites in the United States, Europe and Asia. Five hundred thirty-eight patients were treated with a 10-day course of remdesivir; the other 521 patients received a placebo according to the same schedule. Patients were assessed daily, both to determine the severity of their symptoms as well as the side effects that could be caused by the drug, which interferes with the ability of the virus to copy its RNA.
What did this trial look like?
The main thing measured in this study was the time it took for a patient to recover, using an eight-point clinical scale that ranged from “out of hospital”, increasing the levels of care required and up to “death”. The secondary endpoints of the trial included mortality two and four weeks after starting treatment, as well as any serious side effects that occurred during the trial.
There had been some controversy about the trial because it began in February 2020. Initially, the main outcome measure was the performance of a patient on day 15. However, in late March, statisticians from the have changed this to a secondary result, replacing it with the result described above. But these statisticians did not have access to data showing which participants were receiving the drug and which placebo, nor were they aware of the results. The setting of the study parameters occurred due to an increasing awareness by scientists during these few weeks that COVID-19 was a more prolonged disease than previously thought, and it was therefore logical to study the recovery over 28 days, and not over 15.
At the end of April, it was time to look at the first results of the trial. And these results showed sufficient clinical benefit from the remdesivir that the researchers had an ethical obligation to share their initial results with the wider medical community. It also meant that patients receiving placebo could receive the drug.
Overall, treatment with remdesivir shortened a patient’s recovery time compared to the placebo group, from an average of 15 days to 11 days. Improvements have occurred whether or not the patient receives additional oxygen. In addition, the data help to dispel any concerns about remdesivir, which should be given very soon after symptoms appear. In fact, participants who participated in the trial more than 10 days after the onset of symptoms actually showed a better response to remdesivir than those who started treatment within the first 10 days of symptoms.
The main secondary outcome of the trial – the performance of a participant at day 15 – also showed that remdesivir was significantly better than placebo. And the total number of deaths was lower in the remdesivir group (21 versus 28) at this point, although this difference was not statistically significant. (An analysis of mortality on day 28 is still in progress, since enrollment in the study did not end until the end of April.)
Researchers note that treatment with remdesivir is unlikely to be sufficient on its own, as it has a moderate impact on mortality at best, so studies combining drug treatment with other therapies should be studied. But compared to another recent study on the effect of hydroxychlorquin on COVID-19 – which suggests the drug is causing a marked increase in mortality – this work should certainly be considered a success.
The New England Journal of Medicine, 2020. DOI: 10.1056 / NEJMoa2007764 (About DOI).