Impact of Short-course Colchicine Versus Placebo After Pulmonary Vein Isolation (IMPROVE-PVI Pilot)

Phase 3

Recruiting

• Conditions: Recurrence; Atrial Fibrillation
• Interventions: Drug: Colchicine 0.6 mg; Drug: Matching placebo

• Registration Number: NCT04160117
• Lead Sponsor: Population Health Research Institute

Brief Summary

Recurrence is a common problem after catheter ablation for atrial fibrillation, affecting at least one out of three patients. Inflammation due to the procedure may contribute to pulmonary vein reconnection and, thus, failure of catheter ablation.

This pilot study will assess whether a randomized, placebo-controlled, double-blind trial investigating a 10-day treatment with colchicine, a potent anti-inflammatory drug, to improve patient relevant outcomes after catheter ablation for atrial fibrillation is feasible.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-11-07
• Study First Submitted QC: 2019-11-08
• Study First Posted: 2019-11-12
• Study Start: 2020-01-14
• Status Verified: 2022-09
• Last Update Submitted: 2022-09-19
• Last Update Posted: 2022-09-21
• Primary Completion: 2022-12
• Study Completion: 2023-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

1. Age ≥ 18 years
2. Symptomatic atrial fibrillation and planned catheter-guided first or repeat ablation (pulmonary vein isolation) for atrial fibrillation (radiofrequency or cryoablation energy; concomitant ablation of the cavotricuspid isthmus and other lesions left at the discretion of the treating physician)
3. Written informed consent

Exclusion Criteria

1. Ablation for left atrial tachycardia or isthmus-dependent atrial flutter only (i.e. without pulmonary vein isolation)
2. Administration of a strong inhibitor of CYP3A4 or p-gp (clarithromycin, erythromycin, telithromycin, cyclosporine, ketoconazole or itraconazole)
3. Known hypersensitivity to colchicine
4. Serious gastrointestinal disease (severe gastritis or diarrhea)
5. Clinically overt hepatic disease
6. Severe renal disease (eGFR< 30ml/min/1.73m2)
7. Clinically significant blood dyscrasia (e.g., myelodysplasia)
8. Absolute indication for or ongoing treatment with colchicine
9. Pregnant or breastfeeding women, or women of child-bearing potential who do not use a highly effective form of birth control

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention	Colchicine 0.6 mg	Colchicine 0.6 mg p.o. twice daily for 10 days after catheter ablation for atrial fibrillation
Control	Matching placebo	Matching placebo p.o. twice daily for 10 days after catheter ablation for atrial fibrillation

Primary Outcome Measures

Name	Time	Method
Average monthly enrollment rate	Through study completion (enrollment phase estimated to last 18 months, total study duration estimated to last 24 months)	Average number of patients enrolled per month
Compliance with study treatment	From randomization until 10 days after catheter ablation	Number of provided capsules taken (measured as a proportion of 20 capsules)
Rate of complete follow-up at 6 months	From inception until completion of the study	This will describe the rate of patients for whom the 6-month follow visit can be completed

Secondary Outcome Measures

Name	Time	Method
Rate of signs and symptoms of pericarditis	From randomization until 10 days after catheter ablation	Evidence of new or worsening pericardial effusion on echocardiogram, friction rub on auscultation or pleuritic chest pain
Recurrence of atrial fibrillation within the first 2 weeks after catheter ablation	From randomization until 2 weeks after catheter ablation for atrial fibrillation	Any episode of atrial fibrillation lasting \> 30 seconds within 2 weeks after catheter ablation for atrial fibrillation. Atrial flutter or other forms of atrial tachycardia are included in this definition
Rate of non-infectious diarrhea	From randomization until 10 days after catheter ablation	Three or more loose stools per day, in absence of an overt infectious cause
Recurrence of atrial fibrillation between 10-15 weeks after catheter ablation	Between week 10 and 15 after catheter ablation for atrial fibrillation	Any episode of atrial fibrillation lasting \> 30 seconds between 10-15 weeks after catheter ablation for atrial fibrillation. Atrial flutter or other forms of atrial tachycardia are included in this definition
Rate of all-cause mortality	Through study completion (estimated to be up to 24 months)	This will describe the rate of all-cause mortality during the course of the study.
Rate of patients with composite clinical endpoint	Through study completion (estimated to be up to 24 months)	Emergency department visit: Patient seeking medical attention at any emergency department or Hospitalization for cardiovascular cause: Minimum of one overnight stay in hospital for cardiovascular reason (e.g. recurrence of atrial fibrillation, atrial flutter, atrial tachycardia; hypotension; hypertension; heart failure; myocardial infarction; bleeding, stroke etc.) or Cardioversion: Pharmacological or electrical attempt of or restoring sinus rhythm, irrespective of success of the procedure or Repeat ablation for atrial fibrillation, atrial flutter or left atrial tachycardia: Catheter-guided pulmonary vein isolation, or ablation of cavotricuspid isthmus, or ablation for other left atrial tachycardia (e.g. macro-reentrant tachycardia, focal tachycardia) after the index procedure

Trial Locations

Locations (1)

Hamilton Health Sciences Corporation - Hamilton General Hospital; 🇨🇦 Hamilton, Ontario, Canada