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

• ClinicalTrials.gov Identifier: NCT04322682
• Recruitment Status: Completed
• First Posted: March 26, 2020
• Last Update Posted: January 25, 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

Tracking Information

• First Submitted Date: March 23, 2020
• First Posted Date: March 26, 2020
• Last Update Posted Date: January 25, 2021
• Actual Study Start Date: March 23, 2020
• Actual Primary Completion Date: January 21, 2021 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 25, 2020)

Number of participants who die or require hospitalization due to COVID-19 infection [ Time Frame: 30 days post randomization ]

The primary endpoint will be the composite of death or the need for hospitalization due to COVID-19 infection in the first 30 days after randomization.

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: March 25, 2020)

• Number of participants who die [ Time Frame: 30 days post randomization ]
  The secondary endpoint is the occurrence of death in the 30 days following randomization.
• Number of participants requiring hospitalization due to COVID-19 infection [ Time Frame: 30 days post randomization ]
  The secondary endpoint is the need for hospitalization due to COVID-19 infection in the 30 days following randomization.
• Number of participants requiring mechanical ventilation [ Time Frame: 30 days post randomization ]
  The secondary endpoint is the need for mechanical ventilation in the 30 days following randomization.

• Original Secondary Outcome Measures: Same as current
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Colchicine Coronavirus SARS-CoV2 Trial (COLCORONA)
• Official Title: Colchicine Coronavirus SARS-CoV2 Trial (COLCORONA)
• 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.

• Study Type: Interventional
• Study Phase: Phase 3

Study Design

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

• Condition: Corona Virus Infection

Intervention

• 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
• 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.

Study Arms

• Active Comparator: Colchicine 0.5 mg
  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.
  Intervention: Drug: Colchicine
• 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.
  Intervention: Drug: Placebo oral tablet

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 21, 2021): 4506
• Original Estimated Enrollment (submitted: March 25, 2020): 6000
• Actual Study Completion Date: January 21, 2021
• Actual Primary Completion Date: January 21, 2021 (Final data collection date for primary outcome measure)

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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 40 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Brazil, Canada, South Africa, Spain, United States

Administrative Information

• NCT Number: NCT04322682
• Other Study ID Numbers: MHIPS-2020-001; 3R01HL146206-02S1 ( U.S. NIH Grant/Contract )
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• 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

• IPD Sharing Statement: Not Provided
• Responsible Party: Montreal Heart Institute
• Study Sponsor: Montreal Heart Institute

Collaborators

• 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

• PRS Account: Montreal Heart Institute
• Verification Date: January 2021