Colchicine Coronavirus SARS-CoV2 Trial (COLCORONA) (COVID-19)

• ClinicalTrials.gov Identifier: NCT04322682
• Recruitment Status: Terminated
• First Posted: March 26, 2020
• Results First Posted: September 8, 2021
• Last Update Posted: September 8, 2021
• Sponsor: Montreal Heart Institute
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Bill and Melinda Gates Foundation; The Government of Quebec; DACIMA Software
• Information provided by (Responsible Party): Montreal Heart Institute

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Corona Virus Infection	Drug: Colchicine; Drug: Placebo oral tablet	Phase 3

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 4506 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• 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.
• Masking: Triple (Participant, Care Provider, Investigator)
• Primary Purpose: Treatment
• Official Title: Colchicine Coronavirus SARS-CoV2 Trial (COLCORONA)
• Actual Study Start Date: March 23, 2020
• Actual Primary Completion Date: January 21, 2021
• Actual Study Completion Date: January 21, 2021

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Colchicine; Patients will receive study medication colchicine 0.5 mg per os (PO) twice daily for the first 3 days and then once daily for the last 27 days. If a dose is missed, it should not be replaced.	Drug: Colchicine; Patients in this arm will receive study medication colchicine 0.5 mg per os (PO) twice daily for the first 3 days and then once daily for the last 27 days. If a dose is missed, it should not be replaced.; Other Name: Immuno-modulatory
Placebo Comparator: Placebo; Patients will receive a placebo per os (PO) twice daily for the first 3 days and then once daily for the last 27 days. If a dose is missed, it should not be replaced.	Drug: Placebo oral tablet; Patients will receive the placebo 0.5 mg per os (PO) twice daily for the first 3 days and then once daily for the last 27 days. If a dose is missed, it should not be replaced.

Outcome Measures

Primary Outcome Measures :

1. Number of Participants Who Died or Were Hospitalized Due to COVID-19 Infection in the 30 Days Following Randomization. [ Time Frame: 30 days post randomization ]
   The primary endpoint will be the composite of death or hospitalization due to COVID-19 infection in the 30 days following randomization.

Secondary Outcome Measures :

1. Number of Deaths in the 30 Days Following Randomization. [ Time Frame: 30 days post randomization ]
   The secondary endpoint consisted of two components of the composite primary endpoint and included death in the 30 days following randomization.
2. Number of Participants Who Were Hospitalized Due to COVID-19 Infection in the 30 Days Following Randomization. [ Time Frame: 30 days post randomization ]
   The secondary endpoint consisted of two components of the composite primary endpoint and included hospitalization due to COVID-19 infection in the 30 days following randomization.
3. Number of Participants Who Required Mechanical Ventilation in the 30 Days Following Randomization. [ Time Frame: 30 days post randomization ]
   The secondary endpoint is the need for mechanical ventilation in the 30 days following randomization.

Other Outcome Measures:

1. 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. [ Time Frame: 30 Days post randomization ]
   In the prespecified analysis of the 4159 patients with Covid-19 confirmed by PCR, the primary endpoint (composite of death or hospitalization due to Covid-19 infection in the 30 Days following randomization) was compared between the two treatment groups.

Eligibility Criteria

• Ages Eligible for Study: 40 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

United States, Arizona

Mayo Clinic - Phoenix

Phoenix, Arizona, United States, 85054

Yuma Regional Medical Center Cancer Center

Yuma, Arizona, United States, 85364

United States, California

Centric Health Resources Inc.

Bakersfield, California, United States, 93308

Westside Medical Associates of Los Angeles

Beverly Hills, California, United States, 90211

Rancho Research Institute

Downey, California, United States, 90242

University of California San Francisco - Zuckerberg San Francisco General Hospital

San Francisco, California, United States, 94110

United States, Florida

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States, 32224

South Florida Research Organization

Medley, Florida, United States, 33166

Miami Center for Advanced Cardiology

Miami Beach, Florida, United States, 33140

United States, Minnesota

Mayo Clinic - Rochester

Rochester, Minnesota, United States, 55905

United States, Mississippi

North Mississippi Medical Clinics, Inc.

Tupelo, Mississippi, United States, 38801

United States, New York

New York Langone Health

New York, New York, United States, 10010

United States, North Carolina

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States, 27599

United States, Texas

Baylor Scott & White Research Institute - Pharmacy

Dallas, Texas, United States, 75246

University of Texas(UT) Southwestern Medical Center

Dallas, Texas, United States, 75390

Spring Clinical Research

Houston, Texas, United States, 77002

Brazil

Instituto do Coração (InCor), School of Medicine, University of Sao Paulo

São Paulo, Sao Paulo, Brazil, 05403-900

Hospital Universitário Bragança Paulista

Bragança Paulista, Brazil, 12916-542

Instituto Cruzaltense de Cardiologia

Cruz Alta, Brazil, 98005-020

Hospital de Clínicas de Passo Fundo

Passo Fundo, Brazil, 99010-260

Hospital de Clinicas de Porto Alegre

Porto Alegre, Brazil, 90035-903

Hospital Samaritano Higienópolis

São Paulo, Brazil, 01232-010

Canada, Quebec

Montreal Heart Institute

Montreal, Quebec, Canada, H1T 1C8

Greece

University General Hospital of Athens "Attikon"

Chaïdári, Athens, Greece, 12462

General Hospital of Kozani "Mamatsio"

Kozáni, Greece, 50131

South Africa

Tread Research, Tygerberg Hospital

Cape Town, South Africa, 7500

Spain

Hospital Universitario La Paz, IdiPaz

La Paz, Madrid, Spain, 28046

Hospital Universitario de La Princesa

Madrid, Spain, 28006

Hospital Universitario Ramón y Cajal

Madrid, Spain, 28034

Fundación Jiménez Díaz

Madrid, Spain, 28040

Hospital Universitario 12 de Octubre

Madrid, Spain, 28041

Hospital Universitario Puerta de Hierro Majadahonda

Madrid, Spain, 28222

Sponsors and Collaborators

Montreal Heart Institute

National Heart, Lung, and Blood Institute (NHLBI)

Bill and Melinda Gates Foundation

The Government of Quebec

DACIMA Software

Investigators

• Principal Investigator: Jean-Claude Tardif, MD; Montreal Heart Institute
• Study Director: Zohar Bassevitch, B.SC.; Montreal Health Innovations Coordinating Center

  Study Documents (Full-Text)

Documents provided by Montreal Heart Institute:

Study Protocol  [PDF] May 29, 2020

Statistical Analysis Plan  [PDF] November 25, 2020

More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

• Responsible Party: Montreal Heart Institute
• ClinicalTrials.gov Identifier: NCT04322682
• Other Study ID Numbers: MHIPS-2020-001; 3R01HL146206-02S1 ( U.S. NIH Grant/Contract )
• First Posted: March 26, 2020
• Results First Posted: September 8, 2021
• Last Update Posted: September 8, 2021
• Last Verified: September 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:

Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Colchicine; Gout Suppressants; Antirheumatic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents