Colchicine + Aspirin for Cardiovascular Disease in Type 2 Diabetes

(COLCOT-T2D Trial)

Recruiting at 1 trial location

Overseen By Mylène Provencher, PhD

Age: 18+

Sex: Any

Trial Phase: Phase 3

Sponsor: Montreal Heart Institute

Must not be taking: Antiplatelets, Anticoagulants, Colchicine, NSAIDs

Disqualifiers: Heart disease, Renal insufficiency, Cancer, others

Pivotal Trial (Near Approval) This treatment is in the last trial phase before FDA approval

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: 60 months

10000 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests the effectiveness of colchicine and aspirin, used alone or together, in improving heart health in individuals with type 2 diabetes at high risk for heart problems. Researchers aim to determine if these medications can safely prevent heart issues. Participants should have had type 2 diabetes for at least five years or have related health concerns, such as high cholesterol or smoking habits. The study seeks individuals who have not experienced major heart events, like heart attacks or strokes, in the past. As a Phase 3 trial, this study represents the final step before FDA approval, offering participants a chance to contribute to potentially groundbreaking advancements in heart health.

Do I have to stop taking my current medications to join the trial?

The trial does not specify a general requirement to stop all current medications. However, if you are currently using aspirin, another antiplatelet agent, an anticoagulant, or colchicine for other conditions, you may not be eligible for certain parts of the trial. There is no wash-out period required for colchicine if you stop before enrolling. Please consult with the trial team for specific guidance based on your medications.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that both aspirin and colchicine have been studied for safety in people, including those with type 2 diabetes. Studies indicate that low-dose aspirin is generally safe and can reduce the risk of serious heart problems in people with diabetes, even if they haven't had heart issues before. Aspirin has long been used to protect the heart.

For colchicine, research suggests it is also safe at low doses. In patients with type 2 diabetes who recently had a heart attack, colchicine helped lower the risk of further heart problems and was well-tolerated by most. Although colchicine is usually used for gout, its use in heart disease has shown positive results without major safety concerns.

Both treatments have been tested in similar patient groups and are generally well-tolerated. This is why researchers are studying them further in this trial to confirm their benefits and safety. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about combining colchicine and aspirin for treating cardiovascular disease in people with Type 2 diabetes because this approach targets inflammation and clot formation simultaneously. Colchicine is unique because it reduces inflammation at a cellular level, which is not a focus of most standard treatments like statins or beta-blockers. Aspirin, well-known for its anti-thrombotic effects, complements colchicine by preventing blood clots. This dual-action strategy has the potential to more effectively manage cardiovascular risks associated with diabetes compared to existing options.

What evidence suggests that this trial's treatments could be effective for cardiovascular disease in type 2 diabetes?

Studies have shown that aspirin, which participants in this trial may receive, can lower the risk of serious heart problems in people with diabetes. It helps prevent heart attacks and strokes by reducing the likelihood of blood clots. Research indicates that people with diabetes who took aspirin experienced fewer heart issues compared to those who did not.

Colchicine, another treatment option in this trial, reduced heart-related events in people with type 2 diabetes who had a heart attack. It works by reducing inflammation, which is linked to heart problems. Initial findings suggest that low-dose colchicine may also improve artery health in high-risk patients with type 2 diabetes. Both treatments have shown potential in improving heart health for those with diabetes. ^{1 3 4 6 7}

Are You a Good Fit for This Trial?

This trial is for men and women aged 55 to 80 with type 2 diabetes, without a history of significant heart disease. Participants must not be pregnant or planning pregnancy, should agree to use birth control if applicable, and cannot have severe kidney issues or be on certain medications like chronic steroids or anticoagulants.

Inclusion Criteria

Active cigarette smoking

HbA1c ≥ 8.0% or more in the last 2 years

I have had a stroke or surgery due to severe narrowing of my brain's blood vessels.

Exclusion Criteria

My muscle enzyme levels are more than three times the normal limit and have been confirmed by repeat tests.

My kidney function is low, with an eGFR below 35 mL/min/1.73m2.

I am on long-term medication for inflammation, such as anti-TNF or NSAIDs.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive colchicine and non-enteric coated aspirin, combined or alone, to improve cardiovascular outcomes

60 months

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Aspirin
• Colchicine

Trial Overview The study tests the effectiveness and safety of colchicine and non-enteric coated aspirin, alone or together, in improving heart health outcomes for those at high risk due to type 2 diabetes. It's a comparison between these drugs and their placebos.

How Is the Trial Designed?

Group I: Anti-thrombotic arm Active Control 4 Interventions

For patients eligible for aspirin therapy arm.

Group II: Anti-inflammatory arm Active Control 2 Interventions

For patients ineligible for aspirin therapy arm.

Group III: Anti-inflammatory arm (Placebo) Placebo Group 2 Interventions

For patients ineligible for aspirin therapy arm.

Group IV: Anti-thrombotic arm (Placebo) Placebo Group 4 Interventions

For patients eligible for aspirin therapy arm.

Aspirin is already approved in European Union, United States, Canada, China for the following indications:

Approved in European Union as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in United States as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in Canada as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention
• Preeclampsia prevention

Approved in China as Aspirin for:

• Pain relief
• Fever reduction
• Inflammation
• Cardiovascular disease prevention

Who Is Running the Clinical Trial?

Montreal Heart Institute

Lead Sponsor

Trials

125

Recruited

85,400+

Published Research Related to This Trial

Aspirin is effective for preventing cardiovascular events in patients with a history of vascular disease and may also provide some benefit for primary prevention in the general population, although the benefits are smaller.

In patients with diabetes mellitus, aspirin can reduce the relative risk of myocardial infarction and stroke by about 10%, but it also increases the risk of gastrointestinal bleeding, making low-dose aspirin therapy reasonable for those with a high 10-year risk of cardiovascular events.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin for primary prevention of cardiovascular disease in diabetes mellitus. Pignone, M., Williams, CD.[2023]

In a study involving 2539 patients with type 2 diabetes over a median follow-up of 4.37 years, low-dose aspirin did not significantly reduce the overall risk of atherosclerotic events compared to a nonaspirin group.

However, the aspirin group had a significantly lower incidence of fatal coronary and cerebrovascular events, suggesting that while aspirin may not reduce all cardiovascular risks, it could be beneficial in preventing severe outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. Ogawa, H., Nakayama, M., Morimoto, T., et al.[2023]

In a study of 5,007 patients, including 1,537 with type 2 diabetes, it was found that a significant number of diabetic patients (76.7%) were using aspirin appropriately for primary prevention according to the European Society of Cardiology guidelines, but this dropped to 40.8% and 39.6% for American guidelines.

The study highlighted a common issue of inappropriate aspirin use among diabetic patients, indicating a need for clearer guidelines to help clinicians make better decisions and reduce the misuse of aspirin in primary prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Appropriateness of aspirin use among diabetic patients in primary prevention of atherosclerotic cardiovascular diseases: an analysis of the ASSOS study. Demirci, E., Celik, O., Cil, C., et al.[2023]

In a study involving 2539 patients with type 2 diabetes, low-dose aspirin did not reduce the risk of cardiovascular events over a median follow-up of 10.3 years, indicating it may not be effective for primary prevention in this population.

However, the use of low-dose aspirin was associated with an increased risk of gastrointestinal bleeding, with 2% of patients in the aspirin group experiencing this side effect compared to 0.9% in the no-aspirin group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Patients With Type 2 Diabetes Mellitus: 10-Year Follow-Up of a Randomized Controlled Trial. Saito, Y., Okada, S., Ogawa, H., et al.[2020]

In a study of 28,067 elderly individuals with diabetes, aspirin use did not significantly reduce the risk of myocardial infarction compared to non-users, indicating limited efficacy in this population.

Current aspirin users had approximately double the risk of gastrointestinal bleeding compared to non-users, highlighting the need for careful risk assessment before starting aspirin therapy in elderly patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Myocardial infarction and gastro-intestinal bleeding risks associated with aspirin use among elderly individuals with type 2 diabetes. Sirois, C., Moisan, J., Poirier, P., et al.[2014]

In a study of diabetic patients within the Department of Veterans Affairs, 71% reported receiving counseling about aspirin use, and 66% were taking it daily, indicating improved awareness and usage compared to the early 1990s.

Counseling by healthcare providers was the strongest predictor of aspirin use, and increasing daily aspirin use to 90% could potentially prevent 11,000 myocardial infarctions and save over 8,000 lives, highlighting the importance of this intervention in diabetes care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin use and counseling about aspirin among patients with diabetes. Krein, SL., Vijan, S., Pogach, LM., et al.[2019]

In a study of 100 diabetic patients in Tel Aviv, 61% were prescribed aspirin, indicating a relatively high adherence to guidelines for cardiovascular event prevention, similar to rates in other Western countries.

Younger diabetic patients were less likely to be prescribed aspirin, particularly for secondary prevention, highlighting a need for increased awareness and prescription practices in this demographic.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Factors that influence the implementation of the guidelines for aspirin use by diabetic patients in Israel]. Azuz, N., Thomas, K., Yaffe, Y., et al.[2013]

A systematic review of 7 trials involving 11,618 individuals with diabetes found that aspirin therapy did not significantly reduce major cardiovascular events or all-cause mortality, indicating limited efficacy for primary prevention in this population.

Despite the lack of overall benefit, the analysis suggested that aspirin may have sex-specific effects, potentially reducing the risk of stroke in women and myocardial infarction in men, without significantly increasing the risk of major bleeding.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Aspirin for primary prevention of cardiovascular events in patients with diabetes: A meta-analysis. Zhang, C., Sun, A., Zhang, P., et al.[2013]

In a study of 400 individuals with type 2 diabetes, only 49% were prescribed aspirin, with 42.3% using it for secondary prevention of cardiovascular disease, indicating a gap in appropriate prescribing practices.

Patients receiving shared care were significantly more likely to be prescribed aspirin, while about 10.8% of those with diabetes and cardiovascular disease who met guidelines were not prescribed aspirin, highlighting potential under-treatment in this group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Appropriateness of aspirin prescribing for primary and secondary prevention of cardiovascular disease in type 2 diabetes in different care settings. Tan, SY., Cronin, H., Byrne, S., et al.[2022]

Aspirin is effective as an antiplatelet therapy for preventing cardiovascular diseases, but its efficacy varies by gender and population, showing more coronary event reduction in men and stroke reduction in women.

In diabetic patients, aspirin may offer less protection against cardiovascular complications compared to non-diabetic individuals, and there is a suggestion of increased aspirin resistance, potentially requiring higher dosages for effective prevention.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Aspirin for primary prevention of cardiovascular diseases in diabetic patients: focus on gender difference and insulin resistance]. Legrand, DA., Scheen, AJ.[2015]

In a study involving 31 type 2 diabetic patients and 48 healthy controls, aspirin was found to significantly reduce platelet activity in healthy individuals but had a much lower effect in diabetic patients, indicating reduced sensitivity to aspirin in this group.

The reduced response to aspirin in diabetic patients was linked to poorer metabolic control, as indicated by higher HbA1c levels and lower HDL cholesterol, suggesting that better management of diabetes may improve aspirin efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Reduced sensitivity of platelets from type 2 diabetic patients to acetylsalicylic acid (aspirin)-its relation to metabolic control. Watala, C., Golanski, J., Pluta, J., et al.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4110868/

Acetylsalicylic acid for primary prevention of cardiovascular ... In PHS, it seems that people with and without diabetes benefited from ASA use in primary prevention (diabetes did not modify ASA effect, p = 0.22). ASA use was ...

2. nejm.org nejm.org/doi/full/10.1056/NEJMoa1804988

Effects of Aspirin for Primary Prevention in Persons with ... In conclusion, the use of low-dose aspirin led to a lower risk of serious vascular events than placebo among persons with diabetes who did not ...

3. diabetesjournals.org diabetesjournals.org/care/article/47/1/81/153638/Comparative-Effectiveness-of-Aspirin-Dosing-in

Comparative Effectiveness of Aspirin Dosing in ... Patients with versus without DM had higher rates of the composite cardiovascular outcome (9.6% vs. 5.9%; P < 0.001) and bleeding events (0.78% ...

4. uspreventiveservicestaskforce.org uspreventiveservicestaskforce.org/uspstf/recommendation/aspirin-to-prevent-cardiovascular-disease-preventive-medication

Recommendation: Aspirin Use to Prevent Cardiovascular ... The evidence showed that aspirin use for primary prevention of CVD was associated with a decreased risk of myocardial infarction and stroke but ...

5. ahajournals.org ahajournals.org/doi/10.1161/JAHA.118.010033

Aspirin Use and Cardiovascular Outcome in Patients With ... Our study suggests that aspirin is beneficial in patients with type 2 diabetes mellitus and heart failure, aged ≥55 years, and with no previous ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9487832/

Aspirin in primary prevention of cardiovascular disease ... This study showed promising results of aspirin use in a population, such as people with DM, that is characterized by an increased CVD risk. In the Japanese ...

7. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/2721178

Association of Aspirin Use for Primary Prevention With ... Among participants with diabetes, aspirin use was associated with reductions in the primary composite cardiovascular outcome (HR, 0.90 [95% CrI, ...