Colchicine in Atrial Fibrillation to Prevent Stroke

Phase 3

Completed

• Conditions: Atrial Fibrillation; Stroke
• Interventions: Drug: Colchicine; Drug: Placebo

• Registration Number: NCT02282098
• Lead Sponsor: Population Health Research Institute

Brief Summary

The purpose of this study is to determine the feasibility of performing a randomized controlled trial to investigate the efficacy of an anti-inflammatory drug, colchicine, at reducing well validated markers of thrombosis (D-dimer) and inflammation (hs-CRP).

Detailed Description

Atrial fibrillation (AF), the most common cardiac arrhythmia (with a global burden of 33.5 million affected patients in 2010), is responsible for about 20% of ischemic stroke, a major cause of morbidity and mortality. Anticoagulants are very effective in reducing the risk of stroke in AF but on average 10-15% of treated patients still experience a stroke over a 10-year period and in selected elderly populations the risk is even higher. We hypothesize that thrombosis mediated by inflammation might be responsible for the residual risk of stroke, despite anticoagulant therapy and that targeting inflammation has the potential to reduce thrombosis and the risk of stroke in anticoagulated patients with AF.

Study Timeline

• Study First Submitted: 2014-10-29
• Study First Submitted QC: 2014-10-30
• Study Start: 2014-11
• Study First Posted: 2014-11-04
• Primary Completion: 2020-11-17
• Study Completion: 2020-11-17
• Status Verified: 2021-02
• Last Update Submitted: 2021-02-19
• Last Update Posted: 2021-02-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• Patients with atrial fibrillation who has been receiving chronic anticoagulation for at least 3 months.

Exclusion Criteria

• Contraindications to colchicine such as allergy/hypersensitivity,
• Receiving colchicine or other anti-inflammatory drugs (such as corticosteroids, methotrexate, anti-neoplastic, Interleukin 1-1b antagonist, Tumor necrosis factor-alpha inhibitor),
• Receiving food or co-medications such as strong-moderate cytochrome P450 3A4 inhibitors that will result in elevated plasma level of colchicine,
• Inflammatory disorders (SLE, Rheumatoid arthritis, connective tissue disorder) or chronic infection,
• Severe renal (eGFR< 30ml/min/1.73m2), or liver failure or liver aminotransferase (ALT/AST > 2x Upper limit of normal),
• Moderate or severe cytopenias (platelet < 100, neutrophil count < 1.5) or existing blood dyscrasia (e.g., myelodysplasia)
• Pregnant or lactating woman or woman of child bearing age no protected by reliable contraception.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Active Colchicine	Colchicine	The intervention group will receive colchicine 0.6 mg twice daily orally for 3 months
Placebo Colchicine	Placebo	The control group will receive colchicine placebo 0.6mg twice daily orally for 3 months.

Primary Outcome Measures

Name	Time	Method
Recruitment rates	Randomization to Month 3	Number of eligible patients successfully randomized into study per year of study.
Drop-out rates	Randomization to Month 3	Proportion of participants withdrawing from study for any reason

Secondary Outcome Measures

Name	Time	Method
D-dimer	Randomization to Month 3	Mean D-dimer level at baseline and Month 3 for each arm
hs-CRP	Randomization to Month 3	Mean level of hs-CRP at baseline and month 3 for each arm
Proportion of patients with a clinically significant adverse event	Randomization to Month 3	Proportion of patients with side effects such as diarrhoea, myopathy requiring drug cessation
Drug adherence	Randomization to Month 3	Proportion of missing pill to dispensed pill at 6 weeks and month 3

Trial Locations

Locations (1)

Hamilton General Hospital; 🇨🇦 Hamilton, Ontario, Canada