Colchicine + Aspirin for Cardiovascular Disease in Type 2 Diabetes

(COLCOT-T2D Trial)

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

Trial Summary

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.

What data supports the idea that Colchicine + Aspirin for Cardiovascular Disease in Type 2 Diabetes is an effective drug?

The available research shows that aspirin, when used alone, can help reduce the risk of heart attacks and strokes in people with diabetes, although the benefits are smaller compared to those with a history of heart disease. However, aspirin also increases the risk of stomach bleeding. The studies suggest that aspirin is less effective in diabetic patients compared to non-diabetic ones, possibly due to greater aspirin resistance in diabetics. There is no specific data provided on the combination of Colchicine and Aspirin for cardiovascular disease in type 2 diabetes, so it's unclear how effective this combination is compared to aspirin alone or other treatments. ^{1 2 3 4 5}

What safety data exists for using Colchicine and Aspirin in treating cardiovascular disease in type 2 diabetes?

The provided research primarily focuses on the safety and efficacy of aspirin (acetylsalicylic acid) in diabetic patients for cardiovascular prevention. It highlights that aspirin is generally considered safe and effective for reducing cardiovascular risk, though it may have different effects based on gender and may require higher dosages in diabetic patients due to aspirin resistance. However, there are concerns about gastrointestinal bleeding risks, especially in elderly diabetic patients. The long-term safety of low-dose aspirin remains inconclusive. There is no specific safety data on the combination of Colchicine and Aspirin in the provided research. ^{1 2 6 7 8}

Is aspirin a promising drug for preventing heart disease in people with type 2 diabetes?

Aspirin is considered a helpful drug for preventing heart disease in people with type 2 diabetes, especially for those who already have heart problems. It is recommended by international guidelines for reducing heart-related issues in diabetic patients. ^{1 2 9 10 11}

What is the purpose of this trial?

This trial is testing colchicine and non-coated aspirin, alone or together, to help high-risk type 2 diabetes patients avoid heart problems. Colchicine reduces inflammation, and aspirin helps prevent blood clots.

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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]

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]

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]

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 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]

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 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 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 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]

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]

References

1. United States pubmed.ncbi.nlm.nih.gov

Aspirin use and counseling about aspirin among patients with diabetes. [2019]

2. Belgium pubmed.ncbi.nlm.nih.gov

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

3. Ireland pubmed.ncbi.nlm.nih.gov

Aspirin for primary prevention of cardiovascular events in patients with diabetes: A meta-analysis. [2013]

4. England pubmed.ncbi.nlm.nih.gov

Aspirin for primary prevention of cardiovascular disease in diabetes mellitus. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Reduced sensitivity of platelets from type 2 diabetic patients to acetylsalicylic acid (aspirin)-its relation to metabolic control. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. [2023]

7. United States 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. [2020]

8. England pubmed.ncbi.nlm.nih.gov

Myocardial infarction and gastro-intestinal bleeding risks associated with aspirin use among elderly individuals with type 2 diabetes. [2014]

9. Italy 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. [2023]

10. Ireland 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. [2022]

11. Israel pubmed.ncbi.nlm.nih.gov

[Factors that influence the implementation of the guidelines for aspirin use by diabetic patients in Israel]. [2013]