Efficacy and Safety of Colchicine and Carbaspirin Calcium in Cardiovascular Outcomes for Type 2 Diabetes Patients Without Prior Cardiovascular Events
- Trial ID
- 2024-516646-19-00
- Protocol
- MHICC-2021-001
- Sponsor
- Montreal Heart Institute
Trial statistics
Diseases & Conditions
Objectives
The primary objective of this study is to evaluate the **efficacy** and **safety** of colchicine and non-enteric coated aspirin, either combined or alone, in improving cardiovascular outcomes in high-risk patients with type 2 diabetes. This is clinically relevant as it aims to determine whether low-dose colchicine or non-enteric coated aspirin, when added to standard care, can effectively reduce the risk of a composite of cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, non-fatal stroke, or urgent hospitalization for angina requiring coronary revascularization in adults with diabetes but no evident cardiovascular disease.
Secondary objectives include:
- Determining the efficacy of study treatments on each cardiovascular event of the primary objective, and on the composite of cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, or non-fatal stroke.
- Evaluating the effect of study treatments on the rate of neurocognitive decline using the Montreal Cognitive Assessment (MoCA) test.
- Determining the safety of long-term treatment with colchicine and aspirin, combined or alone, in this patient population.
Participants
The clinical trial involves a total of **5150 participants** who are **type 2 diabetic patients** with no prior cardiovascular events. The study population comprises both **men and women** aged between **55 to 80 years**. Participants were selected based on specific criteria, including a diagnosis of type 2 diabetes treated according to national guidelines and no previous history of coronary artery disease-related clinical events. The trial includes individuals with at least one additional risk factor such as a duration of diabetes of five years or more, elevated HbA1c levels, active cigarette smoking, high hs-CRP, or high coronary calcium score, among others. Participants are required to have the capacity to provide informed consent. Women of childbearing potential must have a negative pregnancy test at screening and agree to use effective birth control throughout the study. The trial population is characterized by a high-risk profile for cardiovascular disease, with lifestyle considerations such as smoking being relevant to the study. The selection process ensures a focus on individuals who are at increased risk for cardiovascular complications, thereby aligning with the trial's objective to evaluate the efficacy and safety of colchicine and non-enteric coated aspirin in improving cardiovascular outcomes.
Plans and Procedures
The clinical trial is designed to evaluate the efficacy and safety of **colchicine** and non-enteric coated aspirin, either combined or alone, in improving cardiovascular outcomes in high-risk patients with type 2 diabetes. This study is a randomized, double-blind, controlled trial, with an estimated duration from January 2025 to December 2027. Participants will be randomly assigned to receive either the active treatment or a placebo, with the primary endpoint being the time from randomization to the first event of a composite of cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, non-fatal stroke, or urgent hospitalization for angina requiring coronary revascularization.
The trial will include several study visits, beginning with a screening visit to assess eligibility based on criteria such as age, diabetes management, and absence of prior coronary artery disease-related clinical events. Following successful screening, participants will undergo randomization and commence treatment. Follow-up visits will occur at regular intervals to monitor safety, efficacy, and any adverse events. The end-of-study visit will conclude the trial, where final assessments will be conducted to evaluate the outcomes.
Participant involvement is expected to last up to 54 weeks, with conditions for early termination including the occurrence of serious adverse events or withdrawal of consent. The trial will adhere to rigorous scientific standards to ensure the reliability and validity of the results, contributing valuable insights into the management of cardiovascular risk in patients with type 2 diabetes.
Treatment
The clinical trial involves the administration of **MIGOUTINE**, a film-coated tablet containing **colchicine** as the active substance. The pharmaceutical form is a film-coated tablet, and the medication is administered orally. The dosage is 0.5 mg per tablet, with a maximum daily dose of 0.5 mg. The treatment period extends up to 54 weeks. Colchicine is a chemical substance with anti-inflammatory properties, and its administration is monitored to ensure compliance with the dosing schedule.
Another experimental treatment in the trial is **carbasalate calcium**, which is administered in a non-enteric coated form. This substance is also given orally, with a maximum daily dose of 80 mg. Carbasalate calcium serves as an analgesic, antipyretic, and anti-inflammatory agent. The treatment duration is similarly set at 54 weeks, and participant adherence to the dosing regimen is closely monitored.
The study also includes the use of placebo tablets to match the experimental medications. One placebo tablet is designed to match the **MIGOUTINE** 0.5 mg film-coated tablet, while another placebo tablet matches the non-enteric coated acetylsalicylic acid. These placebo tablets are used to maintain blinding in the trial and are administered in the same manner as their corresponding active treatments.
Efficacy
The efficacy of the clinical trial titled "COLchicine and non-enteric coated aspirin in the Cardiovascular Outcomes Trial of patients with Type 2 Diabetes (COLCOT-T2D)" will be assessed using specific primary and secondary endpoints. The primary endpoint is defined as the time from randomization to the first occurrence of a composite event, which includes cardiovascular death, resuscitated cardiac arrest, non-fatal myocardial infarction, non-fatal stroke, or urgent hospitalization for angina requiring coronary revascularization. Secondary endpoints include the time from randomization to each component of the primary endpoint, the total burden of first and subsequent primary endpoint events, changes in the Montreal Cognitive Assessment (MoCA) score at yearly follow-ups (excluding the first-year visit) until the end-of-study visit, and the number and proportion of patients experiencing serious adverse events.
The trial aims to evaluate the efficacy and safety of low-dose **colchicine** and non-enteric coated aspirin, either combined or alone, in improving cardiovascular outcomes in high-risk patients with type 2 diabetes. The study will assess whether these treatments, on top of standard care, are effective in reducing the risk of the composite cardiovascular events in adults with diabetes but no evident cardiovascular disease. The efficacy parameters will be measured and collected at specified timepoints, with changes in MoCA scores assessed annually, excluding the first year, until the study's conclusion. The analysis will focus on the time to event for the primary and secondary endpoints, providing insights into the potential benefits of the treatments under investigation.
Inclusion and Exclusion Criteria
Inclusion Criteria
- Men and women aged 55 to 80 years
- Type 2 diabetes treated as per national guidelines
- No previous history of coronary artery disease-related clinical event
- At least one of the following: a. Duration of diabetes of 5 years or more b. HbA1c ≥ 8.0% or more in the last 2 years c. Active cigarette smoking d. High hs-CRP (> 2.0 mg/L) e. High coronary calcium score (Agatston score >100) f. High TG-levels (≥1.7 mmol/L) despite lipid lowering therapy administered as per guidelines g. High LDL-C levels (≥3.5 mmol/L) or high non-HDL-C levels (≥4.2 mmol/L) despite lipid lowering therapy administered as per guidelines h. High Apo-B (≥1.05 g/L) i. Reduced HDL-C (<1.05 mmol/L in men, <1.3 mmol/L in women) j. Lp(a) >50 mg/dL k. Peripheral artery disease with stenosis ≥50% or prior revascularization l. Cerebrovascular disease with stenosis ≥50% or prior revascularization m. Diabetic retinopathy or diabetic neuropathy n. Mild or moderate proteinuria (dipstick analysis) or microalbuminuria
- Women of childbearing potential must have a negative urine pregnancy test at screening/randomization (visit 1) and must agree to use an effective method of birth control throughout the study.
- Patients with the capacity to provide informed consent.
Exclusion Criteria
- Any prior history of myocardial infarction, angina, coronary revascularization, coronary stenosis >30%, stroke, transient ischemic attack, or known heart failure
- Known chronic renal insufficiency defined as an estimated glomerular filtration rate (eGFR), using the MDRD equation, of < 35 mL/min/1.73m2
- 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 and/or low-grade prostate cancer
- Inflammatory bowel disease (Crohn’s disease or ulcerative colitis) or chronic diarrhea
- Peptic ulcer diagnosed within the last 24 months or previous gastrointestinal bleeding, except for mild hemorrhoidal bleeding more than 5 years ago which is permitted (patients meeting this exclusion criterion will not be randomized to receive aspirin or placebo but can be randomized to receive colchicine or placebo)
- Pre-existent progressive neuromuscular disease or known CPK level > 3 times the upper limit of normal as measured within the past 30 days and determined to be non-transient through repeat testing
- Any of the following known parameters as measured within the past 90 days, and determined to be non-transient through repeat testing: a. hemoglobin < 100 g/L b. white blood cell count < 3.0 X 109 /L c. platelet count <110 X 109 /L d. ALT > 3 times the upper limit of normal (ULN) e. total bilirubin > 2 times ULN (unless due to Gilbert syndrome, which is allowed)
- 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
- History of clinically significant drug or alcohol abuse in the last year
- Patient is currently using or plans to begin chronic systemic steroid therapy (oral or intravenous) during the study (topical or inhaled steroids are allowed, as well as replacement corticosteroids for adrenal insufficiency)
- Current chronic treatment with aspirin or another antiplatelet agent (patients meeting this exclusion criterion will not be randomized to receive aspirin or placebo but can be randomized to receive colchicine or placebo)
- Chronic treatment with an anticoagulant agent (patients meeting this exclusion criterion will not be randomized to receive aspirin or placebo but can be randomized to receive colchicine or placebo)
- Current use of colchicine for other indications (mainly chronic indications consisting of 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 enrolment
- History of an allergic reaction or significant sensitivity to colchicine
- History of an allergic reaction or significant sensitivity to aspirin (patients meeting this exclusion criterion will not be randomized to receive aspirin or placebo but can be randomized to receive colchicine or placebo)
- Chronic treatment with an anti-inflammatory agent (for example, anti-TNF-alpha or nonsteroidal anti-inflammatory drug (NSAID))
- Use of an investigational chemical agent less than 30 days or 5 half-lives prior to the screening visit (whichever is longer
- Patient is considered by the investigator, for any reason, to be an unsuitable candidate for the study
Trial Status by Country
| Country | Status | Start of Recruitment | Planned Patients |
|---|---|---|---|
 Denmark | Recruiting | 01 Jan 2025 | 1000 |
 Finland | Recruiting | 01 Jan 2025 | 350 |
 France | Recruiting | 01 Jan 2025 | 1500 |
 Greece | Recruiting | 01 Jan 2025 | 500 |
 Italy | Recruiting | 01 Jan 2025 | 500 |
 Portugal | Recruiting | 01 Jan 2025 | 500 |
Sites & Investigators
Investigational Products
Details about the medicinal products being studied in this clinical trial.
| Product Name | Role in Trial | Formulation | Administration | Max Daily Dose | Treatment Duration | EU MP Number |
|---|---|---|---|---|---|---|
Placebo tablet matching acetylsalicylic acid | Placebo | N/A | — | — | — | N/A |
MIGOUTINE 0,5 mg, comprimé pelliculé | Test | COMPRIMÉ PELLICULÉ | ORAL | 0.5 | 54 | PRD11410991 |
ACETYLSALICYLIC ACID | Test | PHF00059MIG | ORAL | 80 | 54 | SCP131039 |
Placebo tablet matching migoutine 0,5 mg, comprimé pelliculé | Placebo | N/A | — | — | — | N/A |