CIAFS-1: Colchicine in Atrial Fibrillation to Prevent Stroke

Sponsor

Population Health Research Institute (Other)

Overall Status

Completed

CT.gov ID

NCT02282098

Collaborator

(none)

Enrollment

Location

Arms

72.5

Duration (Months)

1.1

Patients Per Site Per Month

Study Details

Study Description

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).

Condition or Disease	Intervention/Treatment	Phase
Atrial Fibrillation Stroke	Drug: Colchicine Drug: Placebo	Phase 3

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 Design

Study Type:

Interventional

Actual Enrollment :

80 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Prevention

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 Start Date :

Nov 1, 2014

Actual Primary Completion Date :

Nov 17, 2020

Actual Study Completion Date :

Nov 17, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Active Colchicine The intervention group will receive colchicine 0.6 mg twice daily orally for 3 months	Drug: Colchicine Colchicine 0.6mg twice daily Other Names: pms-Colchicine
Placebo Comparator: Placebo Colchicine The control group will receive colchicine placebo 0.6mg twice daily orally for 3 months.	Drug: Placebo Placebo Colchicine Other Names: Placebo Capsule

Arm

Intervention/Treatment

Experimental: Active Colchicine

The intervention group will receive colchicine 0.6 mg twice daily orally for 3 months

Drug: Colchicine

Colchicine 0.6mg twice daily

Other Names:

pms-Colchicine

Placebo Comparator: Placebo Colchicine

The control group will receive colchicine placebo 0.6mg twice daily orally for 3 months.

Drug: Placebo

Placebo Colchicine

Other Names:

Placebo Capsule

Outcome Measures

Primary Outcome Measures

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

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Hamilton General Hospital	Hamilton	Ontario	Canada	L8L 2X2

Sponsors and Collaborators

Population Health Research Institute

Investigators

Principal Investigator: Noel Chan, MD, Population Health Research Institute
Principal Investigator: John Eikelboom, MD, Population Health Research Institute