Τίτλος:
Colchicine for community-treated patients with COVID-19 (COLCORONA): a
phase 3, randomised, double-blinded, adaptive, placebo-controlled,
multicentre trial
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Background Evidence suggests a role for excessive inflammation in
COVID-19 complications. Colchicine is an oral anti-inflammatory
medication beneficial in gout, pericarditis, and coronary disease. We
aimed to investigate the effect of colchicine on the composite of
COVID-19-related death or hospital admission. Methods The present study
is a phase 3, randomised, double-blind, adaptive, placebo-controlled,
multicentre trial. The study was done in Brazil, Canada, Greece, South
Africa, Spain, and the USA, and was led by the Montreal Heart Institute.
Patients with COVID-19 diagnosed by PCR testing or clinical criteria who
were not being treated in hospital were eligible if they were at least
40 years old and had at least one high-risk characteristic. The
randomisation list was computer-generated by an unmasked
biostatistician, and masked randomisation was centralised and done
electronically through an automated interactive web-response system. The
allocation sequence was unstratified and used a 1:1 ratio with a
blocking schema and block sizes of six. Patients were randomly assigned
to receive orally administered colchicine (0middot5 mg twice per day for
3 days and then once per day for 27 days thereafter) or matching
placebo. The primary efficacy endpoint was the composite of death or
hospital admission for COVID-19. Vital status at the end of the study
was available for 97middot9% of patients. The analyses were done
according to the intention-to-treat principle. The COLCORONA trial is
registered with ClinicalTrials.gov (NCT04322682) and is now closed to
new participants. Findings Trial enrolment began in March 23, 2020, and
was completed in Dec 22, 2020. A total of 4488 patients (53middot9%
women; median age 54middot0 years, IQR 47middot0-61middot0) were
enrolled and 2235 patients were randomly assigned to colchicine and 2253
to placebo. The primary endpoint occurred in 104 (4middot7%) of 2235
patients in the colchicine group and 131 (5middot8%) of 2253 patients
in the placebo group (odds ratio [OR] 0middot79, 95middot1% CI
0middot61-1middot03; p=0middot081). Among the 4159 patients with
PCR-confirmed COVID-19, the primary endpoint occurred in 96 (4middot6%)
of 2075 patients in the colchicine group and 126 (6middot0%) of 2084
patients in the placebo group (OR 0middot75, 0middot57-0middot99;
p=0middot042). Serious adverse events were reported in 108 (4middot9%)
of 2195 patients in the colchicine group and 139 (6middot3%) of 2217
patients in the placebo group (p=0middot051); pneumonia occurred in 63
(2middot9%) of 2195 patients in the colchicine group and 92
(4middot1%) of 2217 patients in the placebo group (p=0middot021).
Diarrhoea was reported in 300 (13middot7%) of 2195 patients in the
colchicine group and 161 (7middot3%) of 2217 patients in the placebo
group (p<0middot0001). Interpretation In community-treated patients
including those without a mandatory diagnostic test, the effect of
colchicine on COVID-19-related clinical events was not statistically
significant. Among patients with PCR-confirmed COVID-19, colchicine led
to a lower rate of the composite of death or hospital admission than
placebo. Given the absence of orally administered therapies to prevent
COVID-19 complications in community-treated patients and the benefit of
colchicine in patients with PCR-proven COVID-19, this safe and
inexpensive anti-inflammatory agent could be considered for use in those
at risk of complications.
Notwithstanding these considerations, replication in other studies of
PCR-positive community-treated patients is recommended. Funding 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. Copyright (c) 2021 The Author(s). Published by Elsevier Ltd.
This is an Open Access article under the CC BY 4.0 license.
Συγγραφείς:
Tardif, Jean-Claude
Bouabdallaoui, Nadia
L'Allier, Philippe L.
and Gaudet, Daniel
Shah, Binita
Pillinger, Michael H. and
Lopez-Sendon, Jose
da Luz, Protasio
Verret, Lucie
Audet,
Sylvia
Dupuis, Jocelyn
Denault, Andre
Pelletier, Martin and
Tessier, Philippe A.
Samson, Sarah
Fortin, Denis
Tardif,
Jean-Daniel
Busseuil, David
Goulet, Elisabeth
Lacoste,
Chantal
Dubois, Anick
Joshi, Avni Y.
Waters, David D. and
Hsue, Priscilla
Lepor, Norman E.
Lesage, Frederic
Sainturet,
Nicolas
Roy-Clavel, Eve
Bassevitch, Zohar
Orfanos, Andreas
and Stamatescu, Gabriela
Gregoire, Jean C.
Busque, Lambert and
Lavallee, Christian
Hetu, Pierre-Olivier
Paquette,
Jean-Sebastien
Deftereos, Spyridon G.
Levesque, Sylvie and
Cossette, Marieve
Nozza, Anna
Chabot-Blanchet, Malorie
Dube,
Marie-Pierre
Guertin, Marie-Claude
Boivin, Guy
COLCORONA
Investigators
Περιοδικό:
The Lancet Respiratory Medicine
Εκδότης:
Elsevier Sci Ltd, Exeter, United Kingdom
DOI:
10.1016/S2213-2600(21)00222-8
