Colchicine for COVID-19 in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial
Dorward J., Yu LM., Hayward G., Saville BR., Gbinigie O., Van Hecke O., Ogburn E., Evans PH., Thomas NPB., Patel MG., Richards D., Berry N., Detry MA., Saunders C., Fitzgerald M., Harris V., Shanyinde M., de Lusignan S., Andersson MI., Butler CC., Hobbs FDR.
Background Colchicine has been proposed as a COVID-19 treatment. Aim To determine whether colchicine reduces time to recovery and COVID-19-related admissions to hospital and/or deaths among people in the community. Design and setting Prospective, multicentre, open-label, multi-arm, randomised, controlled, adaptive platform trial (PRINCIPLE). Method Adults 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 selfreported recovery and admission to hospital/death related to COVID-19, within 28 days, analysed using Bayesian models. Results The 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 selfreported 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). Conclusion Colchicine did not improve time to recovery in people at higher risk of complications with COVID- 19 in the community.