Colchicine in Atrial Fibrillation to Prevent Stroke (CIAFS-1)

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

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).

Study Overview

• Status: Completed
• Conditions: Stroke; Atrial Fibrillation
• Intervention / Treatment: Drug: Colchicine; Drug: Placebo

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 Type: Interventional
• Enrollment (Actual): 80
• Phase: Phase 3

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Population Health Research Institute
• Investigators: Principal Investigator: Noel Chan, MD, Population Health Research Institute; Principal Investigator: John Eikelboom, MD, Population Health Research Institute

Study record dates

Study Major Dates

• Study Start: November 1, 2014
• Primary Completion (Actual): November 17, 2020
• Study Completion (Actual): November 17, 2020

Study Registration Dates

• First Submitted: October 29, 2014
• First Submitted That Met QC Criteria: October 30, 2014
• First Posted (Estimate): November 4, 2014

Study Record Updates

• Last Update Posted (Actual): February 23, 2021
• Last Update Submitted That Met QC Criteria: February 19, 2021
• Last Verified: February 1, 2021

More Information

Terms related to this study

• Keywords: Stroke; Atrial fibrillation; D-dimer; C-reactive protein; Arrhythmias, Cardiac; agents, anti inflammatory
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Arrhythmias, Cardiac; Stroke; Atrial Fibrillation; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: NIF-14350 (Other Grant/Funding Number: Hamilton Health Science New Investigator Fund)