Colchicine in Atrial Fibrillation to Prevent Stroke

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Atrial Fibrillation, Stroke

Intervention / Treatment
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* Drug: Colchicine
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active Colchicine<br>The intervention group will receive colchicine 0.6 mg twice daily orally for 3 months | Drug: Colchicine<br>* Colchicine 0.6mg twice daily<br>* Other names: pms-Colchicine;|
| Placebo Comparator: Placebo Colchicine<br>The control group will receive colchicine placebo 0.6mg twice daily orally for 3 months. | Drug: Placebo<br>* Placebo Colchicine<br>* Other names: Placebo Capsule;|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

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

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atrial fibrillation, Arrhythmias, Cardiac, Stroke, agents, anti inflammatory, D-dimer, C-reactive protein