Remdesivir failed to reduce mortality in patients with COVID-19 already on ventilators but did exert a slight protective effect against advancement to ventilation or mortality in other hospitalized patients. These findings were reported in the final WHO Solidarity Trial results and updated meta-analyses recently published in Lancet.
The World Health Organization (WHO) initiated the open-label Solidarity Trials (registered with ISRCTN [ISRCTN83971151] and ClinicalTrials.gov [Identifier: NCT04315948]) in March 2020 to compare the efficacy of 4 drugs — lopinavir, hydroxychloroquine, interferon-beta (IFN- β)1a, and remdesivir — in hospitalized patients with severe COVID-19. Notably, all 4 drugs were already approved for other conditions, and 3 of them — lopinavir, hydroxychloroquine, and IFN-β1a — have already been shown to have no value in preventing death from COVID-19 illness.
The Solidarity investigators enlisted 14,304 hospitalized COVID-19 patients from March 22, 2020 through January 29, 2021, from more than 400 hospitals in 35 countries representing all 6 WHO regions. A total of 83 (0.6%) patients were excluded because of an erroneous COVID-19 diagnosis or consent issues, leaving 14,221 participants. For the remdesivir trial, investigators assigned 8275 patients (1:1) to receive remdesivir (n=4146, 10 daily infusions) or a control drug (n=4129). Placebo was not used. The primary outcome was in-hospital mortality and the secondary outcomes were initiation of ventilation and length of hospital stay.
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With respect to mortality, the investigators found that, of the patients receiving remdesivir, 602 (14.5%) died, whereas 643 (15.6%) of those allocated to the control drug died (mortality rate ratio [RR], 0.91; 95% CI, .82-1.02; P =.12). In those already ventilated, 151 (42.1%) of 359 receiving remdesivir expired, compared with 134 (38.6%) of 347 receiving the control drug (RR, 1.13; 95% CI, 0.89-1.42; P =.32).
The data also revealed that 14.6% of all patients who were not ventilated but receiving oxygen and remdesivir died, compared with 16.3% in the control group (RR, 0.87; 95% CI, 0.76-0.99; P =.03). In the 1730 patients not originally receiving oxygen, 2.9% receiving remdesivir expired, compared with 3.8% of the control group (RR, 0.76; 95% CI, 0.46-1.28; P =.30).
Overall, in those not ventilated initially, 11.9% receiving remdesivir expired, vs 13.5% of control (RR, 0.86; 95% CI, 0.76-0.98; P =.02), and 14.1% compared with 15.7% went on to ventilation (RR, 0.88; 95% CI, 0.77-1.00; P =.04). Death or advancement to ventilation was observed in 19.6% of patients in the remdesivir group vs 22.5% in the control group (RR, 0.84; 95% CI, 0.75-0.93; P =.001).
In addition to the Solidarity remdesivir trial, researchers performed meta-analyses of mortality findings in all randomized trials of remdesivir collected by a collaboration among WHO, 5 Cochrane Centers, and 10 additional groups since March, 2020. The meta-analyses produced similar results, confirming remdesivir’s lack of significant positive effects for already ventilated patients in the hospital.
The size of the study was its main limitation, making it difficult for researchers to disprove moderate effects, said study authors; the unavailability of ventilation in some locations also limited the study, they added.
Uncertainty remains the chief attribute of trials involving COVID-19 treatments, the authors noted. “Regardless of how these findings are interpreted, better drugs to treat COVID-19 will continue to be needed,” they concluded. “Oral antiviral agents, various immune modulators, and monoclonal antibodies against currently circulating variants of concern are now emerging that might prove more effective, more convenient, or less expensive than daily remdesivir infusions, but large-scale randomized evidence will be needed to evaluate and compare them,” they advised.
Reference
WHO Solidarity Trial Consortium. Remdesivir and three other drugs for hospitalised patients with COVID-19: final results of the WHO Solidarity randomised trial and updated meta-analyses. Lancet. Published online May 2, 2022. doi:10.1016/S0140-6736(22)00519-0
