Clinical trial NCT04322682: Colchicine Coronavirus SARS-CoV2 Trial (COLCORONA)
Official title: Colchicine Coronavirus SARS-CoV2 Trial (COLCORONA)
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Corona Virus Infection
Lead sponsor: Montreal Heart Institute
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
name: Bill and Melinda Gates Foundation
name: The Government of Quebec
name: Dacima Software Inc.
First posted: 2020-03-26
Enrollment: 4506
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: This will be a randomized, double-blind, placebo-controlled, multi-center study. Following signature of the informed consent form, approximately 6000 subjects meeting all inclusion and no exclusion criteria will be randomized to receive either colchicine or placebo (1:1 allocation ratio) for 30 days. Follow-up phone or video assessments will occur at 15 and 30 days following randomization for evaluation of the occurrence of any trial endpoints or other adverse events.
Primary purpose: TREATMENT

Brief summary: This is a phase 3, randomized, double-blind, placebo-controlled multicenter study to evaluate the efficacy and safety of colchicine in adult patients diagnosed with COVID-19 infection and have at least one high-risk criterion. Approximately 6000 subjects meeting all inclusion and no exclusion criteria will be randomized to receive either colchicine or placebo tablets for 30 days.

Detailed description: The primary objective of this study is to determine whether short-term treatment with colchicine reduces the rate of death and lung complications related to COVID-19. The secondary objective is to determine the safety of treatment with colchicine in this patient population.

Approximately 6000 patients will be enrolled to receive either colchicine or placebo (1:1 allocation ratio) for 30 days. Follow-up assessments will occur at 15 and 30 days following randomization for evaluation of the occurrence of any trial endpoints or other adverse events.

Safety and efficacy will be based on data from randomized patients. An independent data and safety monitoring board (DSMB) will periodically review study results as well as the overall conduct of the study, and will make recommendations to the study Executive Steering Committee (ESC) to continue, stop or modify the study protocol.

Eligibility criteria: Inclusion Criteria:

1. Males and females, at least 40 years of age, capable and willing to provide informed consent;
2. Patient must have received a diagnosis of COVID-19 infection within the last 24 hours;
3. Outpatient setting (not currently hospitalized or under immediate consideration for hospitalization);
4. Patient must possess at least one of the following high-risk criteria: 70 years or more of age, obesity (BMI ≥ 30 kg/m2), diabetes mellitus, uncontrolled hypertension (systolic blood pressure ≥150 mm Hg), known respiratory disease (including asthma or chronic obstructive pulmonary disease), known heart failure, known coronary disease, fever of ≥38.4°C within the last 48 hours, dyspnea at the time of presentation, bicytopenia, pancytopenia, or the combination of high neutrophil count and low lymphocyte count;
5. Female patient is either not of childbearing potential, defined as postmenopausal for at least 1 year or surgically sterile, or is of childbearing potential and practicing at least one method of contraception and preferably two complementary forms of contraception including a barrier method (e.g. male or female condoms, spermicides, sponges, foams, jellies, diaphragm, intrauterine device (IUD)) throughout the study and for 30 days after study completion;
6. Patient must be able and willing to comply with the requirements of this study protocol.

Exclusion Criteria:

1. Patient currently hospitalized or under immediate consideration for hospitalization;
2. Patient currently in shock or with hemodynamic instability;
3. Patient with inflammatory bowel disease (Crohn's disease or ulcerative colitis), chronic diarrhea or malabsorption;
4. Patient with pre-existent progressive neuromuscular disease;
5. Estimated Glomerular filtration rate (eGFR), using the MDRD equation for all subjects being considered for enrollment, with a cut-off of \< 30 mL/m in/1.73m2;
6. Patient with a history of cirrhosis, chronic active hepatitis or severe hepatic disease;
7. Female patient who is pregnant, or breast-feeding or is considering becoming pregnant during the study or for 6 months after the last dose of study medication;
8. Patient currently taking colchicine for other indications (mainly chronic indications represented by Familial Mediterranean Fever or gout);
9. Patient with a history of an allergic reaction or significant sensitivity to colchicine;
10. Patient undergoing chemotherapy for cancer;
11. Patient is considered by the investigator, for any reason, to be an unsuitable candidate for the study.

Primary outcomes:
measure: Number of Participants Who Died or Were Hospitalized Due to COVID-19 Infection in the 30 Days Following Randomization.
timeFrame: 30 days post randomization
Secondary outcomes:
measure: Number of Deaths in the 30 Days Following Randomization.
timeFrame: 30 days post randomization
measure: Number of Participants Who Were Hospitalized Due to COVID-19 Infection in the 30 Days Following Randomization.
timeFrame: 30 days post randomization
measure: Number of Participants Who Required Mechanical Ventilation in the 30 Days Following Randomization.
timeFrame: 30 days post randomization
Other outcomes:
measure: Number of Participants Who Died or Were Hospitalized Due to COVID-19 Infection in the 30 Days Following Randomization in the Subgroup of Patients With PCR-confirmed COVID-19.
timeFrame: 30 Days post randomization
measure: Number of Participants Who Died or Were Hospitalized Due to COVID-19 Infection in the 30 Days Following Randomization by Sex
timeFrame: 30 Days post randomization
measure: Number of Participants Who Died or Were Hospitalized Due to COVID-19 Infection in the 30 Days Following Randomization by Race
timeFrame: 30 Days post randomization
measure: Number of Participants Who Died or Were Hospitalized Due to COVID-19 Infection in the 30 Days Following Randomization by Ethnicity.
timeFrame: 30 Days post randomization
Locations:
city: Phoenix
country: United States
facility: Mayo Clinic - Phoenix
state: Arizona
city: Yuma
country: United States
facility: Yuma Regional Medical Center Cancer Center
state: Arizona
city: Bakersfield
country: United States
facility: Centric Health Resources Inc.
state: California
city: Beverly Hills
country: United States
facility: Westside Medical Associates of Los Angeles
state: California
city: Downey
country: United States
facility: Rancho Research Institute
state: California
city: San Francisco
country: United States
facility: University of California San Francisco - Zuckerberg San Francisco General Hospital
state: California
city: Jacksonville
country: United States
facility: Mayo Clinic - Jacksonville
state: Florida
city: Medley
country: United States
facility: South Florida Research Organization
state: Florida
city: Miami Beach
country: United States
facility: Miami Center for Advanced Cardiology
state: Florida
city: Rochester
country: United States
facility: Mayo Clinic - Rochester
state: Minnesota
city: Tupelo
country: United States
facility: North Mississippi Medical Clinics, Inc.
state: Mississippi
city: New York
country: United States
facility: New York Langone Health
state: New York
city: Chapel Hill
country: United States
facility: University of North Carolina at Chapel Hill
state: North Carolina
city: Dallas
country: United States
facility: Baylor Scott & White Research Institute - Pharmacy
state: Texas
city: Dallas
country: United States
facility: University of Texas(UT) Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: Spring Clinical Research
state: Texas
city: São Paulo
country: Brazil
facility: Instituto do Coração (InCor), School of Medicine, University of Sao Paulo
state: Sao Paulo
city: Bragança Paulista
country: Brazil
facility: Hospital Universitário Bragança Paulista
city: Cruz Alta
country: Brazil
facility: Instituto Cruzaltense de Cardiologia
city: Passo Fundo
country: Brazil
facility: Hospital de Clínicas de Passo Fundo
city: Porto Alegre
country: Brazil
facility: Hospital de Clinicas de Porto Alegre
city: São Paulo
country: Brazil
facility: Hospital Samaritano Higienópolis
city: Montreal
country: Canada
facility: Montreal Heart Institute
state: Quebec
city: Chaïdári
country: Greece
facility: University General Hospital of Athens "Attikon"
state: Athens
city: Kozáni
country: Greece
facility: General Hospital of Kozani "Mamatsio"
city: Cape Town
country: South Africa
facility: Tread Research, Tygerberg Hospital
city: La Paz
country: Spain
facility: Hospital Universitario La Paz, IdiPaz
state: Madrid
city: Madrid
country: Spain
facility: Hospital Universitario de La Princesa
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Madrid
country: Spain
facility: Fundación Jiménez Díaz
city: Madrid
country: Spain
facility: Hospital Universitario 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Puerta de Hierro Majadahonda
Study officials:
affiliation: Montreal Heart Institute
name: Jean-Claude Tardif, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Montreal Health Innovations Coordinating Center
name: Zohar Bassevitch, B.SC.
role: STUDY_DIRECTOR
References:
citation: Mikolajewska A, Fischer AL, Piechotta V, Mueller A, Metzendorf MI, Becker M, Dorando E, Pacheco RL, Martimbianco ALC, Riera R, Skoetz N, Stegemann M. Colchicine for the treatment of COVID-19. Cochrane Database Syst Rev. 2021 Oct 18;10(10):CD015045. doi: 10.1002/14651858.CD015045.
citation: Tardif JC, Bouabdallaoui N, L'Allier PL, Gaudet D, Shah B, Pillinger MH, Lopez-Sendon J, da Luz P, Verret L, Audet S, Dupuis J, Denault A, Pelletier M, Tessier PA, Samson S, Fortin D, Tardif JD, Busseuil D, Goulet E, Lacoste C, Dubois A, Joshi AY, Waters DD, Hsue P, Lepor NE, Lesage F, Sainturet N, Roy-Clavel E, Bassevitch Z, Orfanos A, Stamatescu G, Gregoire JC, Busque L, Lavallee C, Hetu PO, Paquette JS, Deftereos SG, Levesque S, Cossette M, Nozza A, Chabot-Blanchet M, Dube MP, Guertin MC, Boivin G; COLCORONA Investigators. Colchicine for community-treated patients with COVID-19 (COLCORONA): a phase 3, randomised, double-blinded, adaptive, placebo-controlled, multicentre trial. Lancet Respir Med. 2021 Aug;9(8):924-932. doi: 10.1016/S2213-2600(21)00222-8. Epub 2021 May 27.