Clinical trial NCT03845010: Elimination of VPB With Ablation Versus Anti-arrhythmic Drug Treatment
Official title: Elimination of Ventricular Premature Beats With CaTheter Ablation Versus OPtImal Anti-arrhythmic Drug Treatment
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Ventricular Premature Beats
Lead sponsor: Maatschap Cardiologie Zwolle
Sponsor class: OTHER
First posted: 2019-02-19
Enrollment: 22
Sex: ALL
Minimum age (years): 76
Standard ages: OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Intervention model description: Randomized trial comparing catheter ablation with two different potent AADs with different engagement mechanisms in a 1:1:1 ratio with a crossover design in the AAD arm.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Successful therapy
timeFrame: After 3 months
Secondary outcomes:
measure: VPB/VT burden
timeFrame: 3, 6, 12 months after intervention
measure: Change in VPB/VT burden
timeFrame: Before the intervention (baseline) and 3, 6, 12 months after intervention
measure: The impact in terms of total Quality of Life
timeFrame: 3, 6, 12 months after intervention compared to baseline (before intervention)
measure: Association between number of VPB/hour and heart rate (HR)/hour during 24-hours Holter- monitoring
timeFrame: At baseline
measure: Number of pro-arrhythmic effects, (non)-sustained VT or atrial flutter, in AAD arms with frequent visits and use of 24-hour Holter monitoring
timeFrame: 3, 6 and 12 months after intervention
measure: QTc prolongation (sotalol) and QRS broadening (flecainide) with requiring frequent checks with standard ECG and/or treadmill test
timeFrame: 4-6 weeks after first administration of AAD
measure: Complication rate of catheter ablation
timeFrame: Procedure and 3, 6 and 12 months after intervention
measure: Extended evaluation of left ventricular function with transthoracic echo (TTE) (including global longitudinal strain rate measurement)
timeFrame: Baseline, 6 and 12 months after intervention
measure: Absolute and relative difference in VPB/VT burden (%) from baseline, during treatment with sotalol versus treatment with flecainide/verapamil
timeFrame: 3, 6 and 12 months after intervention
measure: 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
timeFrame: 3, 6 and 12 months after intervention
Other outcomes:
Locations:
city: Zwolle
country: Netherlands
facility: Isala hospital
Study officials:
affiliation: Isala
name: Arif Elvan, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: