Coronary Artery DiseasePhase 3COLCOTNCT02551094
Colchicine Cardiovascular Outcomes Trial (COLCOT)
A Phase 3 study testing colchicine in people with Coronary Artery Disease and Myocardial Infarction, run by Montreal Heart Institute at 1 site in Canada.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Coronary Artery Disease, Myocardial Infarction
- What is being tested?
- colchicine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4,745 participants
- Where
- 1 siteCanada
- Study dates
- 4 Dec 2015to 17 Jul 2019
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 16Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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.
Read the 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).
- Conditions
- Coronary Artery Disease, Myocardial Infarction
- Being tested
- colchicine, colchicine placebo
- Medical subject headings
- Coronary Artery Disease, Myocardial Infarction
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
colchicineDrug
Also called no other name
0.5 mg tablet taken once a day
colchicine placeboDrug
Also called no other name
sugar pill manufactured to mimic colchicine 0.5 mg tablet
| Study group | Role | What they receive |
|---|---|---|
| colchicine | Active comparator | 0.5 mg tablet of colchicine taken once a day Receives: Drug: colchicine |
| colchicine placebo | Placebo comparator | 0.5 mg tablet of placebo taken once a day Receives: Drug: colchicine placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
First Event of Cardiovascular Death, Resuscitated Cardiac Arrest, Acute Myocardial Infarction, Stroke, or Urgent Hospitalization for Angina Requiring Coronary Revascularization
The descriptive statistics are the number of participants having at least one of the composites of the primary endpoint.
Measured: From randomization to occurence of first event, assessed up to 3.5 years
Secondary outcomes (7)
Death (Total Mortality)
The descriptive statistics are the number of participants having deceased.
Measured: From randomization to death, assessed up to 3.5 years
Cardiovascular Death
The descriptive statistics are presented as the number of participants having had a cardiovascular death.
Measured: From randomization to death, assessed up to 3.5 years
Resuscitated Cardiac Arrest
The descriptive statistics are presented as the number of participants having had resuscitated cardiac arrest
Measured: From randomization to event, assessed up to 3.5 years
Myocardial Infarction
The descriptive statistics are presented as the number of participants having had myocardial infarction.
Measured: From randomization to event, assessed up to 3.5 years
Stroke
The descriptive statistics are presented as the number of participants having had a stroke.
Measured: From randomization to event, assessed up to 3.5 years
Urgent Hospitalization for Angina Requiring Coronary Revascularization
The descriptive statistics are presented as the number of participants having had urgent hospitalization for angina requiring coronary revascularization.
Measured: From randomization to event, assessed up to 3.5 years
First Event of Cardiovascular Death, Resuscitated Cardiac Arrest, Acute MI or Stroke.
The descriptive statistics are presented as the number of participants having had a first event of cardiovascular death, resuscitated cardiac arrest, acute MI or stroke.
Measured: From randomization to occurence of first event, assessed up to 3.5 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Sep 2015 (estimated)
- Study start4 Dec 2015
- Primary completion17 Jul 2019
- Study completion17 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Coronary Artery DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 4,745 participants (actual)
Sponsor and investigators
- Lead sponsor
- Montreal Heart Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Jean-Claude Tardif, MD, Principal investigator, Montreal Heart InstituteAndreas Orfanos, MD, Study director, Montreal Health Innovations Coordinating Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02551094
- Sponsor's protocol ID
- MHIPS-003
- Acronym
- COLCOT
- Status last verified
- Sep 2020
- First submitted
- 26 Aug 2015
- Last updated
- 19 Oct 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Bouabdallaoui N, Tardif JC, Waters DD, Pinto FJ, Maggioni AP, Diaz R, Berry C, Koenig W, Lopez-Sendon J, Gamra H, Kiwan GS, Blondeau L, Orfanos A, Ibrahim R, Gregoire JC, Dube MP, Samuel M, Morel O, Lim P, Bertrand OF, Kouz S, Guertin MC, L'Allier PL, Roubille F. Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT). Eur Heart J. 2020 Nov 7;41(42):4092-4099. doi: 10.1093/eurheartj/ehaa659.
PubMed 32860034Tardif JC, Kouz S, Waters DD, Bertrand OF, Diaz R, Maggioni AP, Pinto FJ, Ibrahim R, Gamra H, Kiwan GS, Berry C, Lopez-Sendon J, Ostadal P, Koenig W, Angoulvant D, Gregoire JC, Lavoie MA, Dube MP, Rhainds D, Provencher M, Blondeau L, Orfanos A, L'Allier PL, Guertin MC, Roubille F. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med. 2019 Dec 26;381(26):2497-2505. doi: 10.1056/NEJMoa1912388. Epub 2019 Nov 16.
PubMed 31733140
Study at a glance
From the registry record, last updated by the sponsor on 19 Oct 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Colchicine Cardiovascular Outcomes Trial (COLCOT)
- ClinicalTrials.gov ID
- NCT02551094
- Acronym / sponsor ID
- COLCOT / MHIPS-003
- Conditions
- Coronary Artery Disease, Myocardial Infarction
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 4,745 participants (actual)
- Lead sponsor
- Montreal Heart InstituteUniversity, hospital or other
- Study start
- 4 Dec 2015 (actual)
- Primary completion
- 17 Jul 2019 (actual)
- Study completion
- 17 Jul 2019 (actual)
- First posted
- 16 Sep 2015 (estimated)
- Results
- Posted 19 Oct 2020
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| colchicine | Active comparator | Drug: colchicine0.5 mg tablet of colchicine taken once a day |
| colchicine placebo | Placebo comparator | Drug: colchicine placebo0.5 mg tablet of placebo taken once a day |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (16 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| colchicineAlso: no other name0.5 mg tablet taken once a day | Drug | colchicine |
| colchicine placeboAlso: no other namesugar pill manufactured to mimic colchicine 0.5 mg tablet | Drug | colchicine placebo |
Primary outcome
First Event of Cardiovascular Death, Resuscitated Cardiac Arrest, Acute Myocardial Infarction, Stroke, or Urgent Hospitalization for Angina Requiring Coronary Revascularization
Time frame: From randomization to occurence of first event, assessed up to 3.5 years
The descriptive statistics are the number of participants having at least one of the composites of the primary endpoint.
7 secondary outcomes
Death (Total Mortality)
Time frame: From randomization to death, assessed up to 3.5 years
Cardiovascular Death
Time frame: From randomization to death, assessed up to 3.5 years
Resuscitated Cardiac Arrest
Time frame: From randomization to event, assessed up to 3.5 years
Myocardial Infarction
Time frame: From randomization to event, assessed up to 3.5 years
Stroke
Time frame: From randomization to event, assessed up to 3.5 years
Urgent Hospitalization for Angina Requiring Coronary Revascularization
Time frame: From randomization to event, assessed up to 3.5 years
First Event of Cardiovascular Death, Resuscitated Cardiac Arrest, Acute MI or Stroke.
Time frame: From randomization to occurence of first event, assessed up to 3.5 years
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 19 Oct 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 32860034Bouabdallaoui N, Tardif JC, Waters DD, Pinto FJ, Maggioni AP, Diaz R, Berry C, Koenig W, Lopez-Sendon J, Gamra H, Kiwan GS, Blondeau L, Orfanos A, Ibrahim R, Gregoire JC, Dube MP, Samuel M, Morel O, Lim P, Bertrand OF, Kouz S, Guertin MC, L'Allier PL, Roubille F. Time-to-treatment initiation of colchicine and cardiovascular outcomes after myocardial infarction in the Colchicine Cardiovascular Outcomes Trial (COLCOT). Eur Heart J. 2020 Nov 7;41(42):4092-4099. doi: 10.1093/eurheartj/ehaa659.
- Derived from this study: PubMed 31733140Tardif JC, Kouz S, Waters DD, Bertrand OF, Diaz R, Maggioni AP, Pinto FJ, Ibrahim R, Gamra H, Kiwan GS, Berry C, Lopez-Sendon J, Ostadal P, Koenig W, Angoulvant D, Gregoire JC, Lavoie MA, Dube MP, Rhainds D, Provencher M, Blondeau L, Orfanos A, L'Allier PL, Guertin MC, Roubille F. Efficacy and Safety of Low-Dose Colchicine after Myocardial Infarction. N Engl J Med. 2019 Dec 26;381(26):2497-2505. doi: 10.1056/NEJMoa1912388. Epub 2019 Nov 16.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jean-Claude Tardif, MD principal investigator
Montreal Heart Institute
Andreas Orfanos, MD study director
Montreal Health Innovations Coordinating Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing colchicine in people with Coronary Artery Disease and Myocardial Infarction, run by Montreal Heart Institute at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 19 Oct 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 19 Oct 2020). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
First Event of Cardiovascular Death, Resuscitated Cardiac Arrest, Acute Myocardial Infarction, Stroke, or Urgent Hospitalization for Angina Requiring Coronary Revascularization (time frame: From randomization to occurence of first event, assessed up to 3.5 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02551094, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 19 Oct 2020.