Design and rationale of the colchicine/statin for the prevention of COVID-19 complications (COLSTAT) trial

Shah, Tayyab; McCarthy, Marianne; Nasir, Irem; Archer, Herb; Ragheb, Elio; Kluger, Jonathan; Kashyap, Nitu; Paredes, Carlos; Patel, Prashant; Lu, Jing; Kandel, Prakash; Song, Christopher; Khan, Mustafa; Haq, Faheem Ul; Ahmad, Rami; Howes, Christopher; Cambi, Brian; Lancaster, Gilead; Cleman, Michael; De La Cruz, Charles; Parise, Helen; Lansky, Alexandra

Background Despite improvement in the standard of care (SOC) for hospitalized COVID-19 patients, rates of morbidity and mortality remain high. There continues to be a need for easily available and cost-effective treatments. Colchicine and rosuvastatin are both safe and well-studied medications with anti-inflammatory and other pleiotropic effects that may provide additional benefits to hospitalized COVID-19 patients. Methods and results The Colchicine/Statin for the Prevention of COVID-19 Complications (COLSTAT) Trial is a pragmatic, open-label, multicenter, randomized trial comparing the combination of colchicine and rosuvastatin in addition to SOC to SOC alone in hospitalized COVID-19 patients. Four centers in the Yale New Haven Health network will enroll a total of 466 patients with 1:1 randomization. The trial will utilize the electronic health record (Epic® Systems, Verona, Wisconsin, USA) at all stages including screening, randomization, intervention, event ascertainment, and follow-up. The primary endpoint is the 30-day composite of progression to severe COVID-19 disease as defined by the World Health Organization ordinal scale of clinical improvement and arterial/venous thromboembolic events. The secondary powered endpoint is the 30-day composite of death, respiratory failure requiring intubation, and myocardial injury. Conclusions The COLSTAT trial will provide evidence on the efficacy of repurposing colchicine and rosuvastatin for the treatment of hospitalized COVID-19 patients. Moreover, it is designed to be a pragmatic trial that will demonstrate the power of using electronic health records to improve efficiency and enrollment in clinical trials in an adapting landscape. Clinical Trial Registration: NCT04472611 (https://clinicaltrials.gov/ct2/show/NCT04472611).