COVID-19 infection is lacking efficacious treatment at the moment. Many therapeutic approaches are still on development while some others, already known for their efficacy in similar virus based diseases, are still under consideration. Remdesivir is an inhibitor of the viral RNA-dependent, RNA polymerase with in vitro inhibitory activity against SARS-CoV-1 and the Middle East respiratory syndrome (MERS-CoV). It has also the ability to inhibit SARS-CoV-2 in vitro. The current study represents an update of a preliminary report after complete follow-up.
The study was designed as a double-blind, randomized, placebo-controlled trial. All patients were hospitalized due to COVID-19 infection. 1062 patients were almost equally randomized to receive intravenous Remdesivir or placebo. Remdesivir was administered with the following schedule: On day 1, 200 mg followed by 100 mg daily for up to 9 additional days. The primary outcome was the time to recovery, defined by either discharge from the hospital or hospitalization for infection-control purposes only at day 29 considering the current available information on COVID-19. Patients’ clinical status was assessed by pre-defined clinical scores. As secondary outcomes multiple parameters were used and mainly attributed to the use of supplemental oxygen, the use of non invasive ventilation, the use of mechanical ventilation or ECMO and finally mortality assessed at days 14 and 29.
The mean age of patients was 58 years old, 64% were males while the median time from symptoms onset to randomization was 9 days. The major co-morbidity was Hypertension, while 45% were considered as suffering from obesity.
Patients in the remdesivir group had a shorter time to recovery than patients in the placebo group (median, 10 days, as compared to 15 days). The above statistical significant difference remained in the severe diseases stratum. The above difference was further amplified when Remdesivir was administered at an earlier stage of the disease. For those patients who were not receiving noninvasive ventilation, high-flow oxygen, invasive ventilation, or ECMO at baseline, the incidence of new related interventions was lower in the Remdesivir group. Interestingly, for those patients who received the above interventions at baseline the whole time period was lower for those who received Remdesivir.
Mortality was lower in the Remdesivir group but lacking statistically significant difference. The incidence of these adverse events was generally similar in the Remdesivir and placebo groups.
###Comments:
The main message from this study is that we have to consider the early administration of drugs like Remdesivir. This could help us to clearly identify any beneficial effect for our patients. Another critical issue is whether the above treatment approach is affected by co-infections which may alter the pre-defined outcomes.