Colchicine Coronavirus SARS-CoV2 Trial (COLCORONA)

Study Overview
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Brief Summary
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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
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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.

Official Title
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Colchicine Coronavirus SARS-CoV2 Trial (COLCORONA)

Conditions
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Corona Virus Infection

Intervention / Treatment
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* Drug: Colchicine
* Drug: Placebo oral tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Males and females, at least 40 years of age, capable and willing to provide informed consent; Patient must have received a diagnosis of COVID-19 infection within the last 24 hours; Outpatient setting (not currently hospitalized or under immediate consideration for hospitalization); 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; 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; Patient must be able and willing to comply with the requirements of this study protocol. Exclusion Criteria: Patient currently hospitalized or under immediate consideration for hospitalization; Patient currently in shock or with hemodynamic instability; Patient with inflammatory bowel disease (Crohn's disease or ulcerative colitis), chronic diarrhea or malabsorption; Patient with pre-existent progressive neuromuscular disease; 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; Patient with a history of cirrhosis, chronic active hepatitis or severe hepatic disease; 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; Patient currently taking colchicine for other indications (mainly chronic indications represented by Familial Mediterranean Fever or gout); Patient with a history of an allergic reaction or significant sensitivity to colchicine; Patient undergoing chemotherapy for cancer; Patient is considered by the investigator, for any reason, to be an unsuitable candidate for the study.

Ages Eligible for Study
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Minimum Age: 40 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional 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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Colchicine<br>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<br>* 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.<br>* Other names: Immuno-modulatory;|
| Placebo Comparator: Placebo<br>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<br>* 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.<br>|

What is the study measuring?
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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 |