Ivermectin for COVID-19 in Adults in the Community (PRINCIPLE): an Open, Randomised, Controlled, Adaptive Platform Trial of Short- and Longer-Term Outcomes

BackgroundColchicine has been proposed as a COVID-19 treatment.AimTo determine whether colchicine reduces time to recovery and COVID-19-related admissions to hospital and/or deaths among people in the community.Design and settingProspective, multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial (PRINCIPLE).MethodAdults aged ≥65 years or ≥18 years with comorbidities or shortness of breath, and unwell for ≤14 days with suspected COVID-19 in the community, were randomised to usual care, usual care plus colchicine (500 µg daily for 14 days), or usual care plus other interventions. The co-primary endpoints were time to first self-reported recovery and admission to hospital/death related to COVID-19, within 28 days, analysed using Bayesian models.ResultsThe trial opened on 2 April 2020. Randomisation to colchicine started on 4 March 2021 and stopped on 26 May 2021 because the prespecified time to recovery futility criterion was met. The primary analysis model included 2755 participants who were SARS-CoV-2 positive, randomised to colchicine (n = 156), usual care (n = 1145), and other treatments (n = 1454). Time to first self-reported recovery was similar in the colchicine group compared with usual care with an estimated hazard ratio of 0.92 (95% credible interval (CrI) = 0.72 to 1.16) and an estimated increase of 1.4 days in median time to self-reported recovery for colchicine versus usual care. The probability of meaningful benefit in time to recovery was very low at 1.8%. COVID-19-related admissions to hospital/deaths were similar in the colchicine group versus usual care, with an estimated odds ratio of 0.76 (95% CrI = 0.28 to 1.89) and an estimated difference of −0.4% (95% CrI = −2.7 to 2.4).ConclusionColchicine did not improve time to recovery in people at higher risk of complications with COVID-19 in the community.