Individual Patient Data Meta-Analysis evaluating Camostat Mesilate to Treat COVID-19 in Community Settings

Abstract

Background: In the COVID-19 pandemic, a number of phase II and III randomized trials were launched to evaluate the effectiveness of camostat, an orally administered TMPRSS2 inhibitor previously approved for other indications, for treating SARS-CoV-2 infections. Owing to the rapidly changing landscape during the pandemic, many of these trials were unable to reach completion. Further, methods for synthesizing data for trials that were launched and not completed were critical. Methods: This study aimed to consolidate global evidence by identifying placebo-controlled, randomized trials of camostat and analyzing their collective clinical and virologic impact on SARS-CoV-2 through an individual participant data meta-analysis. We harmonized data from the included studies and utilized Bayesian statistical models to assess virologic outcomes (measured by the rate of change in viral shedding) and clinical outcomes (based on the time to the first of two consecutive symptom-free days), adjusting for age and sex. Findings: The meta-analysis incorporated data from six countries, totaling 431 patients across the studies; 118 patients contributed data for the primary virologic outcome and 240 for the clinical symptom outcome. Camostat did not improve the rate of change in viral load (difference in rate of change = 0.11 Ct value/day higher, 95% credible interval 2.04 lower to 2.23 higher) or time to symptom resolution (hazard ratio = 0.87, 95% credible interval 0.51, 1.55) when compared to placebo. Interpretation: In a meta-analysis prompted by a fast-changing landscape during the pandemic, we jointly synthesized evidence across multiple trials that did not meet their original recruitment goals. Despite its theoretically promising mode of action, camostat did not demonstrate a statistically significant virologic or clinical benefit in treating COVID-19, highlighting the complexity of drug repurposing in emergency health situations.