Benefits and harms of remdesivir in hospitalized adults with COVID-19 illness: A systematic review with meta-analysis of pivotal clinical trials.

Context: Remdesivir, a nucleotide inhibitor is widely used for treatment of COVID-19 infection. Pivotal phase III trials have been used by drug manufacturers to gain marketing approval for remdesivir. Several reviews have been published evaluating the effectiveness of remdesivir. However, there have been no reviews of the benefits and harms of remdesivir based on information in pivotal trials. Aims/Questions: To critically appraise and summarize the evidence for benefits and harms of remdesivir therapy for COVID-19 illness in adults, using evidence from pivotal clinical trials. Primary outcomes will include overall mortality and serious adverse events. Secondary outcomes will include length of hospital stay, time to death hospitalizations, and overall adverse events. Methods: I will conduct searches across drug regulatory websites and bibliographic databases (e.g. PubMed, the Cochrane COVID-19 trial registry, Embase, the International Clinical Trials Registry Platform from WHO). I will explore grey literature, pursue backward and forward reference searching to optimize enrollment of all pivotal RCTs, and contact corresponding authors of journal publications for additional data when needed. I will extract data from included trials onto customized Excel spreadsheets according to study type, and setting, participant characteristic(s), study duration, and effects of interventions. I will assess the risk of bias using the Cochrane criteria. Randomized participants who received at least one dose of medication will be included in a meta-analysis. I2 values will be used to assess heterogeneity. Sensitivity analyses and subgroup analyses will be used to test the robustness of the overall analyses. Significance: Results from this systematic review will provide an evidence-based summary to clinicians, public policy experts, and health economists on the benefits and harms of remdesivir therapy in COVID-19 positive adults.