• 

WHO’s Solidarity Therapeutics Trial, the largest randomised control trial carried out in the world during the pandemic, has found that four repurposed drugs — remdesivir, interferon, hydroxychloroquine and lopinavir/ritonavir regimes — for the treatment of COVID-19 are not effective.

WHO’s Solidarity Therapeutics Trial, the largest randomised control trial carried out in the world during the pandemic, has found that four repurposed drugs — remdesivir, interferon, hydroxychloroquine and lopinavir/ritonavir regimes — for the treatment of COVID-19 are not effective.

Interim results from the Solidarity Therapeutics Trial, coordinated by the World Health Organization, have now indicated that remdesivir and interferon regimens too appeared to have little or no effect on 28-day mortality or the in-hospital course of COVID-19 among hospitalised patients.

In early July, the interim trial results showed that both hydroxychloroquine and lopinavir/ritonavir produce little or no reduction in the mortality of hospitalised COVID-19 patients when compared to standard of care. As a result, the trial of these two drugs was interrupted with immediate effect. 

ICMR Director-General Dr. Balram Bhargava in a press release said: “The interim
results show that no study drug definitely reduced mortality (in unventilated patients or any other subgroup of entry characteristics) or initiation of ventilation in hospitalized COVID19 patients.”

Posted on preprint server, WHO website

“Remdesivir, hydroxychloroquine, lopinavir and interferon regimens appeared to have little or no effect on hospitalised COVID-19, as indicated by overall mortality, initiation of ventilation and duration of hospital stay,” says a preprint posted on medRxiv server on October 15. Preprints are yet to be peer-reviewed. However, on the same day, the WHO posted on its website the highlights of the trial saying none of the four repurposed drugs were found to effective in either reducing mortality or hospital stay.

“The unpromising overall findings from the regimens tested suffice to refute early hopes, based on smaller or non-randomised studies, that any will substantially reduce inpatient mortality, initiation of ventilation or hospitalisation duration,” the preprint says.

The study, which spans more than 30 countries, looked at the effects of these treatments on overall mortality, initiation of ventilation, and duration of hospital stay in hospitalized patients. “The drug regimens appeared to have little or no effect on hospitalized COVID-19, as indicated by overall mortality, initiation of ventilation and duration of hospital stay,” the preprint says. 

Remdesivir not effective 

The confidence interval (0.79-1.05), which shows the range of death rate ratios comfortably compatible with the weighted average of the findings from all trials “absolutely excludes the suggestion that Remdesivir can prevent a substantial fraction of all deaths”. “Narrower confidence intervals would be helpful (particularly for Remdesivir), but the main need is for better treatments,” the preprint says.

“Other uses of the drugs, for example in treatment of patients in the community or for prevention, would have to be examined using different trials,” WHO says on its website.

The trial was carried out between March 22 and October 4, in 405 hospitals in 30 countries and over 11,200 adults were randomised to get one of the four drugs or standard of care only (control arm) The trial involved 2,750 who received remdesivir, over 950 who received hydroxychloroquine, over 1,400 lopinavir, over 650 interferon plus lopinavir, over 1,400 only interferon, and nearly 4,100 got only standard of care (control arm). 

The primary objective of the trial was to assess effects on whether any of four re-purposed antivirals could at least moderately affect inhospital mortality, and whether any effects differed between moderate and severe disease. (subsequently defined as ventilated when randomised). The secondary outcomes were initiation of ventilation and hospitalisation duration.

Gilead’s stand

However, On October 8, Gilead Sciences Chairman and CEO Daniel O’Day in an open letter said: “Hospitalised patients receiving remdesivir recovered five days faster on average, and in patients with severe disease, seven days faster. These severely ill patients made up 85% of the total study population… Remdesivir [also] reduced the likelihood of patients progressing to more severe stages of the disease where they would require new or additional oxygen support. And thirdly, in the largest group of patients in the study, those on low-flow oxygen, there was a significant reduction in mortality in a post-hoc analysis. In the overall population, the results showed a trend in mortality reduction.”

In a paper published on October 8 in the New England Journal of Medicine (NEJM), the authors note that those who received remdesivir had a “median recovery time of 10 days as compared with 15 days among those who received placebo”. And in the  case of mortality, the paper found that mortality was 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.