Remdesivir does not reduce mortality in ventilated patients with COVID-19
1. No significant decrease in mortality risk was seen in ventilated patients with COVID-19 on remdesivir compared to control.
2. In patients infected with COVID-19 who were not ventilated at the time of randomization, there was a modest reduction in mortality for patients on remdesevir compared to control (p=0.02).
Evidence Rating Level: 1 (Excellent)
Study Rundown: The Solidarity trial is a large, previously reported study on four potential drug treatments for COVID-19 conducted by the World Health Organization (WHO). The drugs included were remdesivir, hydroxychloroquine, lopinavir, and IFN-β1a. Due to lack of supporting evidence, all three drugs other than remdesivir were discontinued after the interim report; therefore, the follow-up results focus solely on remdesivir. Patients were randomized to receive standard of care plus either remdesivir or no drug (control). This study found no statistically significant difference in all-cause mortality between the remdesivir group and the control group. Patients were further stratified by disease severity defined by use of ventilator support or supplemental oxygen. When disease severity is accounted for, it was found that remdesivir conferred a reduced risk of mortality in less severe disease (no oxygen or ventilator support). In patients that were not ventilated, remdesivir significantly reduced mortality risk and risk of progression to ventilation, but this benefit was small. Limitations of this study include lack of placebo and therefore inherently open-label design. Nonetheless, drug trials during the COVID-19 pandemic were a necessity to evaluate promising drugs and therefore necessitated a more flexible design. This study demonstrates the need for further therapy to effectively combat COVID-19 infection.
Click to read the study in the Lancet
Relevant Reading: Repurposed antiviral drugs for COVID-19—interim WHO Solidarity trial results
In-Depth [randomized controlled trial]: The Solidarity trial enrolled 14 221 patients between Mar 22, 2020, and Jan 29, 2021. Patients were aged 18 years old with a clinical diagnosis of COVID-19 with no positive PCR test required. Disease severity was defined by use of ventilation and supplemental oxygen. Participants were randomized to receive remdesivir, hydroxychloroquine, lopinavir, IFN-β1a or no study drug (no placebo) in addition to standard of care. Control groups were created for each drug using the participants given no study drug. The study eventually only continued with remdesivir and dropped the other drugs due to lack of efficacy. In total, 4146 patients received remdesivir and 4129 patients received no study drug (control). In terms of all-cause mortality, there was no statistically significant benefit seen with remdesivir compared to control (rate ratio [RR] 0.91 [95% CI 0.82-1.02], p=0.12). When stratifying by disease severity, the RR for remdesivir versus control was 0.76 in those not on oxygen (p=0.30), 0.87 for those on supplemental oxygen (p=0.03) and 1.13 for those already on ventilator support (p=0.32). This suggests that remdesivir may have a greater effect in less severe cases (p=0.05). Remdesivir was associated with a lower risk of progressing to ventilator support in those not already ventilated compared to the control group (RR 0.88, p=0.04). When combining the outcomes of death and progression to ventilation in those not on ventilator support, there was a lower risk seen with remdesivir compared to control (0.84, p=0.001), but this effect is small (19.6% vs 22.5%).
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