Clinical trial NCT02282098: Colchicine in Atrial Fibrillation to Prevent Stroke
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atrial Fibrillation
Stroke
Keywords: Atrial fibrillation
Arrhythmias, Cardiac
Stroke
agents, anti inflammatory
D-dimer
C-reactive protein
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
First posted: 2014-11-04
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

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.

Primary outcomes:
measure: Recruitment rates
timeFrame: Randomization to Month 3
measure: Drop-out rates
timeFrame: Randomization to Month 3
Secondary outcomes:
measure: D-dimer
timeFrame: Randomization to Month 3
measure: hs-CRP
timeFrame: Randomization to Month 3
measure: Proportion of patients with a clinically significant adverse event
timeFrame: Randomization to Month 3
measure: Drug adherence
timeFrame: Randomization to Month 3
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
Study officials:
affiliation: Population Health Research Institute
name: Noel Chan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Population Health Research Institute
name: John Eikelboom, MD
role: PRINCIPAL_INVESTIGATOR
References: