Covid-19 living Data

Colchicine vs Standard care/Placebo (RCT)

Mild outpatients

FOREST PLOTS -2022-04-29

Studies description

Trial ISRCTN86534580
Publication PRINCIPLE - Dorward J, medRxiv (2021) (preprint)
Dates: 2021-03-04 to 2021-05-26
Funding: Public/non profit (UK Research and Innovation and the Department of Health and Social Care through the National Institute for Health Research)
Conflict of interest: No

Methods
	RCT Blinding: Unblinded
	Location : Multicenter / UK Follow-up duration (days): 28
Inclusion criteria	Aged ≥65 years, or 50-65 years with comorbidities ongoing symptoms from polymerase chain reaction (PCR) confirmed or suspected COVID-19 (high temperature and/or new, continuous cough and/or change in sense of smell/taste), which had started within the previous 14 days aged 18-65 years with comorbidities (heart disease hypertension asthma or lung disease diabetes hepatic impairment stroke or neurological problems weakened immune system e.g. chemotherapy and self-reported obesity or body mass index ≥35 kg/m2) or shortness of breath.
Exclusion criteria	Already taking colchicine or colchicine contraindicated according to the British National Formulary
Interventions
	Treatment Colchicine 500 mcg orally once a day for 14 days
	Control Standard care
Participants
	Randomized NR Analyzed 276 participants Colchicine=156 Standard care=120
	Characteristics of participants N= 276 Mean age : NR 145 males Severity : Mild: n= 314/ Asymptomatic: n=0
Primary outcome
	In the register Hospital admission or mortality related to suspected COVID-19.
	In the report 1) time to first reported recovery defined as the first instance that a participant reports feeling recovered; and 2) hospitalisation or death related to COVID-19
Documents avalaible	Protocol Yes. In English Statistical plan Yes Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the pre-print article, the trial registry, protocol, statistical analysis plan and supplementary results were used in data extraction and assessment of risk of bias. The primary outcome indicated in registry does not reflect the primary outcome reported in the paper but is reflected in the protocol amendment. The article reports on a colchicine/usual care comparison that is part of an ongoing multi-treatment platform study. Results have been extracted for the population concurrently randomized to colchicine or usual care to mitigate the potential effect of temporal changes in risk. Recruitment to the colchicine arm was terminated after interim analysis revealed futility.

Trial NCT04322682
Publication COLCORONA - Tardif JC, Lancet Respir Med (2021) (published paper)
Dates: 2020-03-23 to 2020-12-22
Funding: Public/non profit ( The Government of Quebec, the Bill & Melinda Gates Foundation, the National Heart, Lung, and Blood Institute of the US National Institutes of Health, the Montreal Heart Institute Foundation, the NYU Grossman School of Medicine, the Rudin Family Foundation, and philanthropist Sophie Desmarais.)
Conflict of interest: Yes

Methods
	RCT Blinding: double blinding
	Location : Multicenter / Brazil, Canada, Greece, South Africa, Spain, USA Follow-up duration (days): 30
Inclusion criteria	Patients ≥ 40 years of age received a diagnosis of COVID-19 within 24 hours of enrollment not currently hospitalized and not under immediate consideration for hospitalization presented at least one of the following high-risk criteria: age of 70 years or older, obesity (body-mass index of 30 kg/m2 or more), diabetes, uncontrolled hypertension (systolic blood pressure ≥150 mm Hg), known respiratory disease, known heart failure, known coronary disease, fever of at least 38.4°C within the last 48 hours, dyspnea at the time of presentation, bicytopenia, pancytopenia, or the combination of high neutrophil and low lymphocyte counts women not of childbearing potential or practicing adequate contraception
Exclusion criteria	Inflammatory bowel disease, chronic diarrhea or malabsorption pre-existent progressive neuromuscular disease estimated glomerular filtration rate less than 30 ml/minute/1.73 m2 severe liver disease current treatment with colchicine current chemotherapy for cancer history of significant sensitivity to colchicine
Interventions
	Treatment Colchicine 0.5 mg twice daily days 1-3, then once daily the following 27 days.
	Control Placebo
Participants
	Randomized NR Analyzed 4488 participants Colchicine=2235 Placebo=2253
	Characteristics of participants N= 4488 Mean age : NR 2067 males Severity : Mild: n= / Asymptomatic: n=
Primary outcome
	In the register Number of participants who die or require hospitalization due to COVID-19 infection [ Time Frame: 30 days post randomization ]
	In the report Composite of death or hospitalization due to COVID-19 infection in the 30 days following randomization
Documents avalaible	Protocol NR Statistical plan NR Data-sharing willing stated in the publication: Yes
Risk of bias Overall The overall risk of bias reported in the table corresponds to the highest risk of bias for the outcomes assessed for the systematic review	Some concerns
General comment	In addition to the pre-print article, the prospective trial registry and study website were used in data extraction and assessment of risk of bias. There were no substantive differences between the pre-print article and the trial registry. The study was terminated early due to logistical issues related to maintaining the central study call center active 24 hours per day for a prolonged period of time, as well as the need to provide healthcare systems with study results in a timely fashion given the state of the COVID-19 pandemic. At termination, 75% of the planned patients were recruited and had completed the 30-day follow-up.