Colchicine Coronavirus SARS-CoV2 Trial (COLCORONA)

NCT ID: NCT04322682

Last Updated: 2024-12-13

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 4506 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-03-23
• Study Completion Date: 2021-01-21

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.

Conditions

Corona Virus Infection

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

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.

Group Type: ACTIVE_COMPARATOR

Colchicine

Intervention Type: DRUG

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.

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.

Group Type: PLACEBO_COMPARATOR

Placebo oral tablet

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: DRUG

Other Intervention Names

Immuno-modulatory

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.

• Minimum Eligible Age: 40 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role: collaborator

Bill and Melinda Gates Foundation

OTHER

Sponsor Role: collaborator

The Government of Quebec

OTHER_GOV

Sponsor Role: collaborator

Dacima Software Inc.

INDUSTRY

Sponsor Role: collaborator

Montreal Heart Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Jean-Claude Tardif, MD

Role: PRINCIPAL_INVESTIGATOR

Montreal Heart Institute

Zohar Bassevitch, B.SC.

Role: STUDY_DIRECTOR

Montreal Health Innovations Coordinating Center

Locations

Mayo Clinic - Phoenix

Phoenix, Arizona, United States

Yuma Regional Medical Center Cancer Center

Yuma, Arizona, United States

Centric Health Resources Inc.

Bakersfield, California, United States

Westside Medical Associates of Los Angeles

Beverly Hills, California, United States

Rancho Research Institute

Downey, California, United States

University of California San Francisco - Zuckerberg San Francisco General Hospital

San Francisco, California, United States

Mayo Clinic - Jacksonville

Jacksonville, Florida, United States

South Florida Research Organization

Medley, Florida, United States

Miami Center for Advanced Cardiology

Miami Beach, Florida, United States

Mayo Clinic - Rochester

Rochester, Minnesota, United States

North Mississippi Medical Clinics, Inc.

Tupelo, Mississippi, United States

New York Langone Health

New York, New York, United States

University of North Carolina at Chapel Hill

Chapel Hill, North Carolina, United States

Baylor Scott & White Research Institute - Pharmacy

Dallas, Texas, United States

University of Texas(UT) Southwestern Medical Center

Dallas, Texas, United States

Spring Clinical Research

Houston, Texas, United States

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

São Paulo, São Paulo, Brazil

Hospital Universitário Bragança Paulista

Bragança Paulista, , Brazil

Instituto Cruzaltense de Cardiologia

Cruz Alta, , Brazil

Hospital de Clínicas de Passo Fundo

Passo Fundo, , Brazil

Hospital de Clinicas de Porto Alegre

Porto Alegre, , Brazil

Hospital Samaritano Higienópolis

São Paulo, , Brazil

Montreal Heart Institute

Montreal, Quebec, Canada

University General Hospital of Athens "Attikon"

Chaïdári, Athens, Greece

General Hospital of Kozani "Mamatsio"

Kozani, , Greece

Tread Research, Tygerberg Hospital

Cape Town, , South Africa

Hospital Universitario La Paz, IdiPaz

La Paz, Madrid, Spain

Hospital Universitario de La Princesa

Madrid, , Spain

Hospital Universitario Ramón y Cajal

Madrid, , Spain

Fundación Jiménez Díaz

Madrid, , Spain

Hospital Universitario 12 de Octubre

Madrid, , Spain

Hospital Universitario Puerta de Hierro Majadahonda

Madrid, , Spain

Countries

United States; Brazil; Canada; Greece; South Africa; Spain

References

Alfehaid LS, Farah S, Omer A, Weber BN, Alkhezi O, Tawfik YMK, Shah AM, Libby P, Buckley LF. Drug-Drug Interactions and the Clinical Tolerability of Colchicine Among Patients With COVID-19: A Secondary Analysis of the COLCORONA Randomized Clinical Trial. JAMA Netw Open. 2024 Sep 3;7(9):e2431309. doi: 10.1001/jamanetworkopen.2024.31309.

Reference Type: DERIVED

PMID: 39240567 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34658014 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 34051877 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Statistical Analysis Plan

View Document

Other Identifiers

3R01HL146206-02S1

Identifier Type: NIH

Identifier Source: secondary_id

View Link

MHIPS-2020-001

Identifier Type: -

Identifier Source: org_study_id