Clinical trial NCT04160117: Impact of Short-course Colchicine Versus Placebo After Pulmonary Vein Isolation (IMPROVE-PVI Pilot)
Official title: Impact of Short-course Colchicine Versus Placebo After Pulmonary Vein Isolation (IMPROVE-PVI): a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Atrial Fibrillation
Recurrence
Lead sponsor: Population Health Research Institute
Sponsor class: OTHER
First posted: 2019-11-12
Enrollment: 202
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Average monthly enrollment rate
timeFrame: Through study completion (enrollment phase estimated to last 18 months, total study duration estimated to last 24 months)
measure: Compliance with study treatment
timeFrame: From randomization until 10 days after catheter ablation
measure: Rate of complete follow-up at 6 months
timeFrame: From inception until completion of the study
Secondary outcomes:
measure: Rate of non-infectious diarrhea
timeFrame: From randomization until 10 days after catheter ablation
measure: Rate of signs and symptoms of pericarditis
timeFrame: From randomization until 10 days after catheter ablation
measure: Recurrence of atrial fibrillation within the first 2 weeks after catheter ablation
timeFrame: From randomization until 2 weeks after catheter ablation for atrial fibrillation
measure: Recurrence of atrial fibrillation between 10-15 weeks after catheter ablation
timeFrame: Between week 10 and 15 after catheter ablation for atrial fibrillation
measure: Rate of patients with composite clinical endpoint
timeFrame: Through study completion (estimated to be up to 24 months)
measure: Rate of all-cause mortality
timeFrame: Through study completion (estimated to be up to 24 months)
Other outcomes:
Locations:
city: Hamilton
country: Canada
facility: Hamilton Health Sciences Corporation - Hamilton General Hospital
state: Ontario
Study officials:
affiliation: Population Health Research Institute
name: Alexander Benz, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Benz AP, Amit G, Connolly SJ, Singh J, Acosta-Velez JG, Conen D, Deif B, Divakaramenon S, McIntyre WF, Mtwesi V, Roberts JD, Wong JA, Zhao R, Healey JS; IMPROVE-PVI Investigators. Colchicine to Prevent Atrial Fibrillation Recurrence After Catheter Ablation: A Randomized, Placebo-Controlled Trial. Circ Arrhythm Electrophysiol. 2024 Jan;17(1):e01238. doi: 10.1161/CIRCEP.123.012387. Epub 2023 Dec 21.