Evaluating colchicine for inflammation in patients with diabetes and cardiovascular events

The Canadian Study of Arterial Inflammation in Patients With Diabetes and Recent Vascular Events: EvaluatioN of Colchicine Effectiveness (CADENCE)

This study is testing whether colchicine can help reduce inflammation in heart-related plaque for people with diabetes who have recently had a heart attack or stroke.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 115 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Ottawa Heart Institute Research Corporation (Academic / other)
• Drugs / interventions: methotrexate, prednisone
• Locations: 2 sites (Edmonton, Alberta and 1 other locations)
• Trial ID: NCT04181996 on ClinicalTrials.gov

What this trial studies

This study aims to assess the effects of colchicine on plaque inflammation in patients with diabetes or pre-diabetes who have recently experienced cardiovascular events such as myocardial infarction or stroke. Utilizing 18F-fluorodeoxyglucose (FDG) PET imaging, the study will investigate the mechanisms by which colchicine may reduce inflammation in atherosclerotic plaques. By understanding how colchicine works, the study seeks to optimize patient selection for anti-inflammatory therapies in cardiovascular disease. The trial will compare the effects of colchicine against a placebo in a controlled setting.

Who should consider this trial

Good fit: Ideal candidates include adults aged 18 and older with type 2 diabetes or pre-diabetes who have suffered a recent cardiovascular event.

Not a fit: Patients who have planned revascularization procedures or whose recent cardiovascular events are deemed embolic may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could lead to improved treatment options for patients at high risk of cardiovascular events due to inflammation.

How similar studies have performed: Previous studies, such as the LoDoCo and COLCOT trials, have shown promising results for colchicine in reducing cardiovascular events, indicating a potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

Patients who have:

1. Type 2 Diabetes (on diet, oral hypo-glycemic agents and/or insulin) or pre-diabetes (defined by Diabetes Canada as HbA1C=6.0-6.45% or increased fasting blood sugar (FBS) (6.1-6.9 mmol/L) or impaired glucose tolerance);
2. suffered a recent cardiovascular event (≤120 days post ACS (i.e. STEMI or nonSTEMI) or TIA/stroke with associated large vessel atherosclerotic disease confirmed on US, CT or MRI;
3. stable symptoms and hemodynamics;
4. age ≥18 years;
5. given informed consent. Standard definitions will be used for STEMI, NSTEMI, and for ischemic stroke confirmed by CT or MRI and TIA confirmed by a neurologist.

Exclusion Criteria:

Patients who have

1. planned revascularization of infarct or stroke related artery more than 120 days after the qualifying/index event;
2. a recent CV event likely to have been embolic in the opinion of the neurologist or cardiologist;
3. recent CV event likely to have been secondary to myocardial infarction with non-obstructive coronary arteries (MINOCA) in the opinion of the cardiologist;
4. severe LV dysfunction (EF\<30%);
5. severe valve disease requiring intervention;
6. decompensated heart failure;
7. active infection (e.g. pneumonia, active skin infections, and on antibiotics);
8. chronic diarrhea;
9. immune compromise (e.g. recurrent infection);
10. history of cancer within the last 3 years (other than a successfully treated cutaneous squamous cell or basal cell carcinoma or localized carcinoma in situ of the cervix).
11. active inflammatory conditions (e.g. rheumatoid arthritis, chronic inflammatory bowel disease, SLE, systemic anti-inflammatory therapy (e.g. prednisone, methotrexate));
12. pregnancy (all women of child bearing potential will have a negative BHCG test;
13. breastfeeding;
14. Women of childbearing potential who refuse to use two forms of contraception (this includes at least one form of highly effective and one effective method of contraception) throughout the study OR men capable of fathering a child who refuse to use contraception.
15. glomerular filtration rate (GFR) \<50 ml/min/1.72m2
16. Use of potent p-glycoprotein inhibitors (i.e. systemic cyclosporine, clarithromycin, or systemic ketoconazole) or a strong CYP3A4 inhibitor (i.e. ritonavir, clarithromycin, or systemic ketoconazole);
17. Hemoglobin \< 105(women) \<110 (men) g/L; WBC \< 3.0x 10(9)/L, platelet count\< 110x 10(9)/L;
18. Patient with a history of cirrhosis, chronic active hepatitis or severe hepatic disease or with alanine aminotransferase (ALT) levels greater than 3 times the upper limit of normal.
19. unable to give informed consent;
20. TIA/Stroke patients with atrial fibrillation

Exclusion for CTA portion of the protocol:

Patients with dye allergy or those with GRF \<60 will not undergo CTA but will have PET/CT.

Where this trial is running

Edmonton, Alberta and 1 other locations

• Mazankowski Alberta Heart Institute — Edmonton, Alberta, Canada (Recruiting)
• University of Ottawa Heart Institute — Ottawa, Ontario, Canada (Recruiting)

Study contacts

• Principal investigator: Kevin Boczar, MD — Ottawa Heart Institute Research Corporation
• Study coordinator: Chantal Lefebvre, BScN

Conditions Cardiovascular Diseases; Atherosclerosis; Inflammation; Diabetes; Imaging, PET, inflammation, Biomarkers, Colchicine