Ventricular Premature Beats
Conditions
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.
Interventions
DRUGSotalol
Patients will be titrated to the maximal tolerated dose of sotalol with a targeted dose of 80 thrice daily (TID)
DRUGFlecainide 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
PROCEDURECatheter ablation
Patients will undergo VPB/VT ablation using a percutaneous transfemoral approach according to standard clinical routine
Sponsors
Maatschap Cardiologie Zwolle
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
NONE
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.
Eligibility
Sex/Gender
ALL
Age
76 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Successful therapy | After 3 months | Number of patients reaching succesfull therapy defined as \>80% reduction of of VPB/VT burden after 3 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in VPB/VT burden | Before the intervention (baseline) and 3, 6, 12 months after intervention | Measurement in different subgroups e.g.: males, pre and post-menopausal women |
| The impact in terms of total Quality of Life | 3, 6, 12 months after intervention compared to baseline (before intervention) | 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. |
| Association between number of VPB/hour and heart rate (HR)/hour during 24-hours Holter- monitoring | At baseline | 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 |
| 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 | — |
| VPB/VT burden | 3, 6, 12 months after intervention | — |
| Complication rate of catheter ablation | Procedure and 3, 6 and 12 months after intervention | In all patients with special interest to the subgroup of patients with anatomically challenging origin of (non-RVOT) VPB/VTs |
| 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 | — |
| 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 | — |
Countries
Netherlands
Outcome results
None listed