Atrial Fibrillation, Stroke
Conditions
Keywords
Atrial fibrillation, Arrhythmias, Cardiac, Stroke, agents, anti inflammatory, D-dimer, C-reactive protein
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.
Interventions
DRUGColchicine
Colchicine 0.6mg twice daily
DRUGPlacebo
Placebo Colchicine
Sponsors
Population Health Research Institute
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Canada
Outcome results
None listed