Colchicine for Prevention of Vascular Inflammation in Non-cardio Embolic Stroke

• Status: Unknown status
• Trial end date: 2021-10-01
• Target enrollment: 0
• Participant gender: All

Summary

This study evaluates the use of Colchicine in adults over 40 years of age who have suffered an ischaemic stroke or transient ischaemic attack NOT caused by cardiac embolism or other defined causes. Patients will be randomised to 0.5 mg/day of Colchicine plus usual care, or to usual care alone.

To investigate the efficacy of low dose colchicine (0.5mg/day) plus usual care (defined as antiplatelet, lipid-lowering, antihypertensive treatment, and appropriate lifestyle advice) compared with usual care alone to prevent non-fatal recurrent ischaemic stroke, myocardial infarction, cardiac arrest, hospitalization for unstable angina and vascular death after ischaemic stroke or transient ischaemic attack (TIA) not caused by cardiac embolism or other defined causes unrelated to atherosclerosis

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University College Dublin
• Collaborators: Health Research Board, Ireland; Irish Heart Foundation; National University of Ireland, Galway, Ireland; Universitaire Ziekenhuizen Leuven; Universitat de Lleida; University of Athens; University of Edinburgh; University of Limerick
• Treatments: Colchicine

Criteria

Inclusion Criteria:

1. Written informed consent consistent with ICH-GCP guidelines and local laws signed prior to all trial-related procedures.

2. Age 40 years or greater

3. Either,

• ischaemic stroke without major disability (modified Rankin score 3 or less)

• or high-risk TIA

4. Qualifying stroke/TIA probably caused by large artery stenosis, small artery occlusion (lacunar stroke), or cryptogenic embolism, with cardiac embolism or other defined stroke mechanism deemed unlikely in the opinion of the treating physician.

5. GFRgreater than or equal to 50 ml/min.

6. In the opinion of the treating physician, patient is medically-stable, capable of participating in a randomised trial, and willing to attend follow-up.

Exclusion Criteria:

1. Cardio-embolic stroke/TIA, probably caused by identified atrial fibrillation (permanent or paroxysmal), in the opinion of the treating physician.

2. Cardio-embolic stroke/TIA probably caused by other identified cardiac source (intra-cardiac thrombus, endocarditis, metallic heart valve, low ejection fraction <30%), in the opinion of the treating physician.

3. Stroke/TIA caused by dissection, endocarditis, paradoxical embolism, drug use, venous thrombosis, within 48 hours aftercarotid or cardiac surgery, hypercoagulability states, migraine, or inherited cerebrovascular disorders (eg. Fabry's disease, CADASIL), in the opinion of the treating physician.

4. History of myopathy or myalgias with raised creatine kinase (CK) on statin therapy.

5. Blood dyscrasia defined as anaemia (haemoglobin <10g/dL), thrombocytopenia (platelet count <150 x109/L) or leucopenia (white cell count <4 x109/L) at randomisation.

6. Impaired hepatic function (transaminases greater than twice upper limit of normal) at randomisation.

7. Concurrent treatment with moderate or strong CYP3A4 inhibitors (clarithromycin, erythromycin, telithromycin, other macrolide antibiotics, ketoconazole, itraconazole, voriconazole, ritonavir, atazanavir, indinavir, other HIV protease inhibitors, verapamil, diltiazem, quinidine, digoxin, disulfiram) or P-gp inhibitors (cyclosporine) at randomisation.

8. Symptomatic peripheral neuropathy and pre-existing progressive neuromuscular disease

9. Inflammatory bowel disease (Crohn's or ulcerative colitis) or chronic diarrhoea.

9. Dementia, sufficient to impair independence in basic activities of daily living.

10. Active malignancy, known hepatitis B or C, or HIV infection prior to qualifying stroke/TIA.

11. Impaired swallow preventing oral administration of study medication. 12. History of poor medication compliance. 13. Unlikely to comply with study procedures and follow-up visits due to severe or fatal comorbid illness or other factor (eg. inability to travel for follow up visits), in opinion of randomising physician.

14. Pregnancy, breast-feeding, or pre-menopausal women 15. Patient concurrently participating in another clinical trial with an investigational drug or device, or use of investigational drug within 30 days or 5 half-lives before the Screening visit (whichever is longer) 16. Known allergy or sensitivity to colchicine.