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Colchicine Cardiovascular Outcomes Trial (COLCOT) (COLCOT)

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ClinicalTrials.gov Identifier: NCT02551094
Recruitment Status : Completed
First Posted : September 16, 2015
Last Update Posted : October 15, 2019
Sponsor:
Information provided by (Responsible Party):
Montreal Heart Institute

Brief Summary:
The study evaluates whether long-term treatment with colchicine reduces rates of cardiovascular events in patients after myocardial infarction. Patients who have suffered a documented acute myocardial infarction within the last 30 days, are treated according to the national guidelines and after having completed any planned percutaneous revascularization procedures associated with their initial infarction will receive either colchicine (0.5 mg per day) or matching placebo (1:1 allocation ratio) for an estimated 2 years period or until the target of 301 primary endpoints has been reached.

Condition or disease Intervention/treatment Phase
Coronary Artery Disease Myocardial Infarction Drug: colchicine Drug: colchicine placebo Phase 3

Detailed Description:
Atherosclerosis is the most common cause of myocardial infarction, stroke and peripheral arterial disease. Research has clearly demonstrated that inflammation plays a key role in the initiation, progression and manifestations of atherosclerosis. Atherosclerotic lesions begin as an accumulation of lipid-laden cells (primarily macrophages) beneath the endothelium, and progress with the further accumulation of cells, connective-tissue elements, lipids and debris through immunological and inflammatory activation. Neutrophils and other inflammatory cells have been shown to invade culprit atherosclerotic lesions in acute coronary syndromes. It is likely that the inflammatory process is responsible for the high rate of cardiovascular events despite significant advances in the treatment of risk factors such as hypercholesterolemia and hypertension. It is vital to improve our understanding of the inflammatory nature of atherosclerotic disease and modify the inflammatory process with targeted therapies. Prospective cohort studies have consistently shown that high sensitivity C-reactive protein (hs-CRP) and several other biomarkers of inflammation are independently associated with increasing risk of future cardiovascular events in different populations. This together with animal models showing that reduced inflammation has anti-atherosclerotic effects, create the impetus to test the hypothesis that treatment of the underlying inflammatory process will contribute to improved cardiovascular clinical outcomes. Colchicine is an inexpensive, yet potent, anti-inflammatory drug approved for acute use in patients with gout and chronic use in patients with Familial Mediterranean Fever. The mechanism of action is through the inhibition of tubulin polymerization and potentially also through effects on cellular adhesion molecules and inflammatory chemokines. Colchicine may also have direct anti-inflammatory effects by inhibiting key inflammatory signaling networks known as the inflammasome and pro-inflammatory cytokines. Through the disruption of the cytoskeleton, colchicine is believed to suppress secretion of cytokines and chemokines as well as in vitro platelet aggregation. Considerable work has highlighted the potential of colchicine in the treatment of cardiovascular diseases mediated by pro-inflammatory processes. More recently colchicine has been evaluated for its effect on cardiovascular events in patients with coronary artery disease (CAD).

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 4745 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: Colchicine Cardiovascular Outcomes Trial (COLCOT)
Actual Study Start Date : December 4, 2015
Actual Primary Completion Date : July 17, 2019
Actual Study Completion Date : July 17, 2019

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Heart Attack
Drug Information available for: Colchicine

Arm Intervention/treatment
Active Comparator: colchicine
0.5 mg tablet of colchicine taken once a day
Drug: colchicine
0.5 mg tablet taken once a day
Other Name: no other name

Placebo Comparator: colchicine placebo
0.5 mg tablet of placebo taken once a day
Drug: colchicine placebo
sugar pill manufactured to mimic colchicine 0.5 mg tablet
Other Name: no other name




Primary Outcome Measures :
  1. Time from randomization to the first event of cardiovascular death, resuscitated cardiac arrest, acute myocardial infarction, stroke, or urgent hospitalization for angina requiring coronary revascularization [ Time Frame: approximately 1.5 to 3.5 years ]

Secondary Outcome Measures :
  1. Time from randomization to death (total mortality) [ Time Frame: approximately 1.5 to 3.5 years ]
  2. Time from randomization to cardiovascular death [ Time Frame: approximately 1.5 to 3.5 years ]
  3. Time from randomization to resuscitated cardiac arrest [ Time Frame: approximately 1.5 to 3.5 years ]
  4. Time from randomization to myocardial infarction [ Time Frame: approximately 1.5 to 3.5 years ]
  5. Time from randomization to stroke [ Time Frame: approximately 1.5 to 3.5 years ]
  6. Time from randomization to urgent hospitalization for angina requiring coronary revascularization [ Time Frame: approximately 1.5 to 3.5 years ]
  7. Time from randomization to the first event of cardiovascular death, resuscitated cardiac arrest, acute MI or stroke. [ Time Frame: approximately 1.5 to 3.5 years ]

Other Outcome Measures:
  1. Time from randomization to the first event of deep venous thrombosis or pulmonary embolus [ Time Frame: approximately 1.5 to 3.5 years ]
  2. Time from randomization to atrial fibrillation [ Time Frame: approximately 1.5 to 3.5 years ]
  3. Time from randomization to heart failure hospitalization [ Time Frame: approximately 1.5 to 3.5 years ]
  4. Time from randomization to coronary revascularization [ Time Frame: approximately 1.5 to 3.5 years ]


Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Males and females of at least 18 years of age capable and willing to provide informed consent
  • Patient must have suffered a documented acute myocardial infarction within the last 30 days
  • Patient must be treated according to national guidelines (including anti-platelet therapy, statin, renin-angiotensin-aldosterone system inhibitor (preferably angiotensin-converting enzyme) and beta-blocker when indicated)
  • Patient must have completed any planned percutaneous revascularization procedures associated with his or her qualifying myocardial infarction
  • Female patient is either not of childbearing potential, defined as postmenopausal for at least one year or surgically sterile, or is of childbearing potential and practicing at least one method of contraception and preferably two complementary forms of contraception
  • Patient is judged to be in good general health as determined by the principal investigator
  • Patient must be able and willing to comply with the requirements of this study protocol

Exclusion Criteria:

  • Patient with a poorly controlled medical condition, such as New York Heart Association Class III-IV heart failure, a left ventricular ejection fraction of less than 35%, recent stroke (within the past 3 months), or any other condition which in the opinion of the investigator, would put the patient at risk if participating in this study
  • Patient with a Type 2 index MI (secondary to ischemic imbalance)
  • Patient with a prior coronary artery bypass graft within the past 3 years, or planned
  • Patient currently in cardiogenic shock or with hemodynamic instability
  • Patient with a history of cancer or lymphoproliferative disease within the last 3 years other than a successfully treated non-metastatic cutaneous squamous cell or basal cell carcinoma and or localized carcinoma in situ of the cervix
  • Patient with inflammatory bowel disease (Crohn's disease or ulcerative colitis) or patient with chronic diarrhea
  • Patient with pre-existent progressive neuromuscular disease or patient with creatine phosphokinase level greater than 3 times the upper limit of normal (unless due to myocardial infarction which is allowed) as measured within the past 30 days and determined to be non-transient through repeat testing
  • Patient with any of the following as measured within the past 30 days, and determined to be non-transient through repeat testing: hemoglobin less than 115 grams/L, white blood cell count less than 3.0 X 10(9)/L,platelet count less than 110 X 10(9)/L, alanine aminotransferase greater than 3 times the upper limit of normal, total bilirubin greater than 2 times the upper limit of normal (unless due to Gilbert syndrome, which is allowed), creatinine greater than 2 times the upper limit of normal
  • Patient with a history of cirrhosis, chronic active hepatitis or sever 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 with a history of clinically significant drug or alcohol abuse in the last year
  • Patient is currently using or plan to begin chronic systemic steroid therapy (oral or intravenous) during the study (topical or inhaled steroids are allowed)
  • Patient currently taking colchicine for other indications (mainly chronic indications represented by Familial Mediterranean Fever or gout); there is no wash-out period required for patients who have been treated with colchicine and stopped treatment prior to enrollment
  • Patient with history of an allergic reaction or significant sensitivity to colchicine
  • Patient who has used an investigational chemical agent less than 30 days or 5 half-lives prior to the screening visit (whichever is longer)
  • Patient is considered by he investigator, for any reason, to be an unsuitable candidate for the study

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02551094


Locations
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Canada, Quebec
Montreal Heart Institute
Montreal, Quebec, Canada, H1T1C8
Sponsors and Collaborators
Montreal Heart Institute
Investigators
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Principal Investigator: Jean-Claude Tardif, MD Montreal Heart Institute

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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Responsible Party: Montreal Heart Institute
ClinicalTrials.gov Identifier: NCT02551094     History of Changes
Other Study ID Numbers: MHIPS-003
First Posted: September 16, 2015    Key Record Dates
Last Update Posted: October 15, 2019
Last Verified: October 2019
Additional relevant MeSH terms:
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Coronary Artery Disease
Coronary Disease
Myocardial Ischemia
Myocardial Infarction
Infarction
Ischemia
Pathologic Processes
Necrosis
Heart Diseases
Cardiovascular Diseases
Arteriosclerosis
Arterial Occlusive Diseases
Vascular Diseases
Colchicine
Gout Suppressants
Antirheumatic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents