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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Recurrence; Atrial Fibrillation
• Intervention / Treatment: Drug: Colchicine 0.6 mg; Drug: Matching placebo

• Study Type: Interventional
• Enrollment (Anticipated): 200
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Alex Benz; Phone Number: 905-521-2100; Email: IMPROVE-PVI@phri.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Recruiting
      • Hamilton Health Sciences Corporation - Hamilton General Hospital
      • Contact: Guy Amit, MD; Phone Number: 44760 905-527-1447; Email: amit@hhsc.ca

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:

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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)

Collaborators and Investigators

• Sponsor: Population Health Research Institute
• Investigators: Principal Investigator: Alexander Benz, MD, Population Health Research Institute

Study record dates

Study Major Dates

• Study Start (Actual): January 14, 2020
• Primary Completion (Anticipated): December 1, 2022
• Study Completion (Anticipated): January 1, 2023

Study Registration Dates

• First Submitted: November 7, 2019
• First Submitted That Met QC Criteria: November 8, 2019
• First Posted (Actual): November 12, 2019

Study Record Updates

• Last Update Posted (Actual): September 21, 2022
• Last Update Submitted That Met QC Criteria: September 19, 2022
• Last Verified: September 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Disease Attributes; Arrhythmias, Cardiac; Atrial Fibrillation; Recurrence; Molecular Mechanisms of Pharmacological Action; Antirheumatic Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Gout Suppressants; Colchicine
• Other Study ID Numbers: IMPROVE-PVI pilot

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No