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

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.

Study Overview

• Status: Terminated
• Conditions: Corona Virus Infection
• Intervention / Treatment: Drug: Colchicine; Drug: Placebo oral tablet

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 Type: Interventional
• Enrollment (Actual): 4506
• Phase: Phase 3

Contacts and Locations

Study Locations

• Brazil
  • Bragança Paulista, Brazil, 12916-542
    • Hospital Universitário Bragança Paulista
  • Cruz Alta, Brazil, 98005-020
    • Instituto Cruzaltense de Cardiologia
  • Passo Fundo, Brazil, 99010-260
    • Hospital de Clínicas de Passo Fundo
  • Porto Alegre, Brazil, 90035-903
    • Hospital de Clínicas de Porto Alegre
  • São Paulo, Brazil, 01232-010
    • Hospital Samaritano Higienópolis
  • Sao Paulo
    • São Paulo, Sao Paulo, Brazil, 05403-900
      • Instituto do Coração (InCor), School of Medicine, University of Sao Paulo
• Canada
  • Quebec
    • Montreal, Quebec, Canada, H1T 1C8
      • Montreal Heart Institute
• Greece
  • Kozáni, Greece, 50131
    • General Hospital of Kozani "Mamatsio"
  • Athens
    • Chaïdári, Athens, Greece, 12462
      • University General Hospital of Athens "ATTIKON"
• South Africa
  • Cape Town, South Africa, 7500
    • Tread Research, Tygerberg Hospital
• Spain
  • Madrid, Spain, 28040
    • Fundacion Jimenez Diaz
  • Madrid, Spain, 28034
    • Hospital Universitario Ramon y Cajal
  • Madrid, Spain, 28041
    • Hospital Universitario 12 de Octubre
  • Madrid, Spain, 28006
    • Hospital Universitario de La Princesa
  • Madrid, Spain, 28222
    • Hospital Universitario Puerta de Hierro Majadahonda
  • Madrid
    • La Paz, Madrid, Spain, 28046
      • Hospital Universitario La Paz, IdiPAZ
• United States
  • Arizona
    • Phoenix, Arizona, United States, 85054
      • Mayo Clinic - Phoenix
    • Yuma, Arizona, United States, 85364
      • Yuma Regional Medical Center Cancer Center
  • California
    • Bakersfield, California, United States, 93308
      • Centric Health Resources Inc.
    • Beverly Hills, California, United States, 90211
      • Westside Medical Associates of Los Angeles
    • Downey, California, United States, 90242
      • Rancho Research Institute
    • San Francisco, California, United States, 94110
      • University of California San Francisco - Zuckerberg San Francisco General Hospital
  • Florida
    • Jacksonville, Florida, United States, 32224
      • Mayo Clinic - Jacksonville
    • Medley, Florida, United States, 33166
      • South Florida Research Organization
    • Miami Beach, Florida, United States, 33140
      • Miami Center for Advanced Cardiology
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Mayo Clinic - Rochester
  • Mississippi
    • Tupelo, Mississippi, United States, 38801
      • North Mississippi Medical Clinics, Inc.
  • New York
    • New York, New York, United States, 10010
      • New York Langone Health
  • North Carolina
    • Chapel Hill, North Carolina, United States, 27599
      • University of North Carolina at Chapel Hill
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor Scott & White Research Institute - Pharmacy
    • Dallas, Texas, United States, 75390
      • University of Texas(UT) Southwestern Medical Center
    • Houston, Texas, United States, 77002
      • Spring Clinical Research

Participation Criteria

Eligibility Criteria

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

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / 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 Names: 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.

What is the study measuring?

Primary Outcome Measures

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

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Deaths in the 30 Days Following Randomization.	The secondary endpoint consisted of two components of the composite primary endpoint and included death in the 30 days following randomization.	30 days post randomization
Number of Participants Who Were Hospitalized Due to COVID-19 Infection in the 30 Days Following 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.	30 days post randomization
Number of Participants Who Required Mechanical Ventilation in the 30 Days Following Randomization.	The secondary endpoint is the need for mechanical ventilation in the 30 days following randomization.	30 days post randomization

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	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.	30 Days post randomization

Collaborators and Investigators

• Sponsor: Montreal Heart Institute
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); Bill and Melinda Gates Foundation; The Government of Quebec; DACIMA Software
• Investigators: Study Director: Zohar Bassevitch, B.SC., Montreal Health Innovations Coordinating Center

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Actual): March 23, 2020
• Primary Completion (Actual): January 21, 2021
• Study Completion (Actual): January 21, 2021

Study Registration Dates

• First Submitted: March 23, 2020
• First Submitted That Met QC Criteria: March 25, 2020
• First Posted (Actual): March 26, 2020

Study Record Updates

• Last Update Posted (Actual): September 8, 2021
• Last Update Submitted That Met QC Criteria: September 3, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Coronaviridae Infections; Nidovirales Infections; RNA Virus Infections; Virus Diseases; Infections; Coronavirus Infections; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: MHIPS-2020-001; 3R01HL146206-02S1 (U.S. NIH Grant/Contract)

Drug and device information, study documents

• 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