Elimination of VPB With Ablation Versus Anti-arrhythmic Drug Treatment (ECTOPIA)

Elimination of Ventricular Premature Beats With CaTheter Ablation Versus OPtImal Anti-arrhythmic Drug Treatment

The ECTOPIA trial is a randomized, multicenter, clinical trial to assess elimination of ventricular premature beats (VPB) with catheter ablation versus optimal anti-arrhythmic drugs (AAD) treatment with flecainide/verapamil or sotalol.

Study Overview

• Status: Completed
• Conditions: Ventricular Premature Beats
• Intervention / Treatment: Drug: Sotalol; Drug: Flecainide and verapamil; Procedure: Catheter ablation

Detailed Description

The ECTOPIA trial is a randomized, multicenter, clinical trial to assess elimination of VPB with catheter ablation versus optimal AAD treatment with flecainide/verapamil or sotalol. Due to the use of different AAD (with and without beta-blocking abilities) the investigators will be able to explore the secondary objectives. Finally, this study will assess safety of ablation of non-RVOT VPBs and long-term treatment with two different AAD.

• Study Type: Interventional
• Enrollment (Actual): 22
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Netherlands
  • Zwolle, Netherlands
    • Isala Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 74 years and older (Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Patients willing and capable to provide written informed consent
• Patients with frequent symptomatic VPB and/or nonsustained VTs with burden ≥ 5% on 24 hour Holter monitor AND
• Absence of structural heart disease (excluded by echocardiogram) AND
• Absence of underlying cardiac ischemia (ruled out by treadmill test, CT coronary arteries, nuclear scintigraphy or coronary angiography) AND
• Patient is considered an acceptable candidate for catheter ablation treatment with a dominant morphology of VPB/VT origin judged by the treating physician.
• For those already undergoing treatment, all antiarrhythmic drugs including digitalis must be discontinued during a 2-week washout period before entry to the study

Exclusion Criteria:

• Age >75 years
• Previous catheter ablation therapy for VPB/VT
• Patients with sustained ventricular tachycardia or cardiac channelopathies (e.g. Catecholaminergic polymorphic ventricular tachycardia (CPVT), long- or short QT syndrome, Brugada syndrome)
• Wolff-parkinson-white (WPW) syndrome
• Use of medication with risk of QTc prolongation (e.g. antidepressant, antiemetic), except for study medication sotalol.
• Left ventricular dysfunction (LV ejection fraction <55%)
• Estimated glomerular filtration rate < 50 ml/min/1.73 m2
• Hepatic impairment defined by a total bilirubin ≥ 2 times the upper limit (ULN) of normal, or alanine aminotransferase (ALAT) or aspartate aminotransferase (ASAT) ≥ 3 times ULN at screening
• Untreated hypo- or hyperthyroidism or electrolyte imbalance
• Untreated obstructive sleep apnea
• Patients with history of myocardial infarction or bypass surgery
• More than grade 1/3 valvular regurgitation and/or significant valve stenosis (moderate or severe)
• Contraindication for any of the antiarrhythmic drugs used in this study
• Enrolment in another clinical study
• Woman currently pregnant or breastfeeding or not using reliable contraceptive measures during fertile age
• Mental or physical inability to participate in the study
• Life expectancy ≤ 12 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Sotalol	Drug: Sotalol; Patients will be titrated to the maximal tolerated dose of sotalol with a targeted dose of 80 thrice daily (TID)
Active Comparator: Flecainide and verapamil	Drug: Flecainide and verapamil; Patients will receive maximal tolerated dose of flecainide and verapamil with titration to a maximal dose of 200 mg of flecainide and 240 mg of verapamil per day
Active Comparator: Catheter ablation	Procedure: Catheter ablation; Patients will undergo VPB/VT ablation using a percutaneous transfemoral approach according to standard clinical routine

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Successful therapy	Number of patients reaching succesfull therapy defined as >80% reduction of of VPB/VT burden after 3 months	After 3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VPB/VT burden		3, 6, 12 months after intervention
Change in VPB/VT burden	Measurement in different subgroups e.g.: males, pre and post-menopausal women	Before the intervention (baseline) and 3, 6, 12 months after intervention
The impact in terms of total Quality of Life	Use of the University of Toronto AF severity scale (AFSS) questionnaire to measure Quality of Life. The total score range is 0-35. Seven questions in total with a maximum score of 5 points per question.	3, 6, 12 months after intervention compared to baseline (before intervention)
Association between number of VPB/hour and heart rate (HR)/hour during 24-hours Holter- monitoring	A scatterplot will be made in order to depict the association between the number of VBP/hour and heart rate (HR)/hour during 24-hour Holter-monitoring	At baseline
Number of pro-arrhythmic effects, (non)-sustained VT or atrial flutter, in AAD arms with frequent visits and use of 24-hour Holter monitoring		3, 6 and 12 months after intervention
QTc prolongation (sotalol) and QRS broadening (flecainide) with requiring frequent checks with standard ECG and/or treadmill test		4-6 weeks after first administration of AAD
Complication rate of catheter ablation	In all patients with special interest to the subgroup of patients with anatomically challenging origin of (non-RVOT) VPB/VTs	Procedure and 3, 6 and 12 months after intervention
Extended evaluation of left ventricular function with transthoracic echo (TTE) (including global longitudinal strain rate measurement)		Baseline, 6 and 12 months after intervention
Absolute and relative difference in VPB/VT burden (%) from baseline, during treatment with sotalol versus treatment with flecainide/verapamil		3, 6 and 12 months after intervention
Divide patients in three groups depending on HR dependency of VPB/VT and compare absolute and relative difference in VPB/VT burden (%) from baseline, during treatment with sotalol versus treatment with flecainide/verapamil		3, 6 and 12 months after intervention

Collaborators and Investigators

• Sponsor: Maatschap Cardiologie Zwolle
• Investigators: Principal Investigator: Arif Elvan, MD, PhD, Isala

Study record dates

Study Major Dates

• Study Start (Actual): February 12, 2019
• Primary Completion (Actual): January 17, 2023
• Study Completion (Actual): January 17, 2023

Study Registration Dates

• First Submitted: January 17, 2019
• First Submitted That Met QC Criteria: February 14, 2019
• First Posted (Actual): February 19, 2019

Study Record Updates

• Last Update Posted (Actual): June 28, 2023
• Last Update Submitted That Met QC Criteria: June 27, 2023
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Pregnancy Complications; Obstetric Labor Complications; Obstetric Labor, Premature; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Premature Birth; Cardiac Complexes, Premature; Ventricular Premature Complexes; Physiological Effects of Drugs; Adrenergic beta-Antagonists; Adrenergic Antagonists; Adrenergic Agents; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Anti-Arrhythmia Agents; Vasodilator Agents; Autonomic Agents; Peripheral Nervous System Agents; Membrane Transport Modulators; Voltage-Gated Sodium Channel Blockers; Sodium Channel Blockers; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Sympatholytics; Verapamil; Flecainide; Sotalol
• Other Study ID Numbers: 10407

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