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Randomized Controlled Trial
. 2022 Jun 30;72(720):e446-e455.
doi: 10.3399/BJGP.2022.0083. Print 2022 Jul.

Colchicine for COVID-19 in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial

Jienchi Dorward  1 , Ly-Mee Yu  2 , Gail Hayward  2 , Benjamin R Saville  3 , Oghenekome Gbinigie  2 , Oliver Van Hecke  2 , Emma Ogburn  2 , Philip H Evans  4 , Nicholas Pb Thomas  5 , Mahendra G Patel  2 , Duncan Richards  6 , Nicholas Berry  7 , Michelle A Detry  7 , Christina Saunders  7 , Mark Fitzgerald  7 , Victoria Harris  2 , Milensu Shanyinde  2 , Simon de Lusignan  8 , Monique I Andersson  9 , Christopher C Butler  2 , Fd Richard Hobbs  2 ; PRINCIPLE Trial Collaborative Group
Affiliations
Randomized Controlled Trial

Colchicine for COVID-19 in the community (PRINCIPLE): a randomised, controlled, adaptive platform trial

Jienchi Dorward et al. Br J Gen Pract. .

Abstract

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 self-reported 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 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).

Conclusion: Colchicine did not improve time to recovery in people at higher risk of complications with COVID-19 in the community.

Keywords: COVID-19; colchicine; community; primary health care; randomised controlled trial.

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Figures

Figure 1.
Figure 1.
Participant flow diagram. aParticipants provided no diary information. bAnalysis for secondary outcomes.
Figure 2.
Figure 2.
Time to first-reported recovery. a) SARS-CoV-2-positive primary analysis population. b) Concurrent randomisation SARS-CoV-2-positive population.
Figure 2.
Figure 2.
Time to first-reported recovery. a) SARS-CoV-2-positive primary analysis population. b) Concurrent randomisation SARS-CoV-2-positive population.
Figure 3.
Figure 3.
Forest plot of subgroup analysis of time to first-reported recovery (concurrent randomisation and eligible SARS-CoV-2-positive population. HR = hazard ratio. ICS = inhaled corticosteroids.
See this image and copyright information in PMC

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