Targeting Inflammation in Atrial Fibrillation to Prevent Ischemic Stroke: A Feasibility Study Evaluating the Effect of Colchicine on D-dimer and Hs-CRP in Anticoagulated Patients With Atrial Fibrillation
Overview
- Phase
- Phase 3
- Intervention
- Colchicine
- Conditions
- Atrial Fibrillation
- Sponsor
- Population Health Research Institute
- Enrollment
- 80
- Locations
- 1
- Primary Endpoint
- Recruitment rates
- Status
- Completed
- Last Updated
- 5 years ago
Overview
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.
Investigators
Noel Chan
PI
Population Health Research Institute
Eligibility Criteria
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.
Arms & Interventions
Active Colchicine
The intervention group will receive colchicine 0.6 mg twice daily orally for 3 months
Intervention: Colchicine
Placebo Colchicine
The control group will receive colchicine placebo 0.6mg twice daily orally for 3 months.
Intervention: Placebo
Outcomes
Primary Outcomes
Recruitment rates
Time Frame: Randomization to Month 3
Number of eligible patients successfully randomized into study per year of study.
Drop-out rates
Time Frame: Randomization to Month 3
Proportion of participants withdrawing from study for any reason
Secondary Outcomes
- D-dimer(Randomization to Month 3)
- hs-CRP(Randomization to Month 3)
- Proportion of patients with a clinically significant adverse event(Randomization to Month 3)
- Drug adherence(Randomization to Month 3)