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

Study Overview
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Brief Summary
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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.

Official Title
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Impact of Short-course Colchicine Versus Placebo After Pulmonary Vein Isolation (IMPROVE-PVI): A Pilot Study

Conditions
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Atrial Fibrillation, Recurrence

Intervention / Treatment
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* Drug: Colchicine 0.6 mg
* Drug: Matching placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥ 18 years 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) Written informed consent Exclusion Criteria: Ablation for left atrial tachycardia or isthmus-dependent atrial flutter only (i.e. without pulmonary vein isolation) Administration of a strong inhibitor of CYP3A4 or p-gp (clarithromycin, erythromycin, telithromycin, cyclosporine, ketoconazole or itraconazole) Known hypersensitivity to colchicine Serious gastrointestinal disease (severe gastritis or diarrhea) Clinically overt hepatic disease Severe renal disease (eGFR< 30ml/min/1.73m2) Clinically significant blood dyscrasia (e.g., myelodysplasia) Absolute indication for or ongoing treatment with colchicine Pregnant or breastfeeding women, or women of child-bearing potential who do not use a highly effective form of birth control

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention<br>Colchicine 0.6 mg p.o. twice daily for 10 days after catheter ablation for atrial fibrillation | Drug: Colchicine 0.6 mg<br>* p.o. twice daily for 10 days after catheter ablation for atrial fibrillation<br>|
| Placebo Comparator: Control<br>Matching placebo p.o. twice daily for 10 days after catheter ablation for atrial fibrillation | Drug: Matching placebo<br>* p.o. twice daily for 10 days after catheter ablation for atrial fibrillation<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Rate of non-infectious diarrhea | Three or more loose stools per day, in absence of an overt infectious cause | From randomization until 10 days after catheter ablation | 
| Rate of signs and symptoms of pericarditis | Evidence of new or worsening pericardial effusion on echocardiogram, friction rub on auscultation or pleuritic chest pain | From randomization until 10 days after catheter ablation | 
| Recurrence of atrial fibrillation within the first 2 weeks after catheter ablation | 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 | From randomization until 2 weeks after catheter ablation for atrial fibrillation | 
| Recurrence of atrial fibrillation between 10-15 weeks after catheter ablation | 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 | Between week 10 and 15 after catheter ablation for atrial fibrillation | 
| Rate of patients with composite clinical endpoint | 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 | Through study completion (estimated to be up to 24 months) | 
| Rate of all-cause mortality | This will describe the rate of all-cause mortality during the course of the study. | Through study completion (estimated to be up to 24 months) |