STereotactic Ablative Radiosurgery of Recurrent Ventricular Tachycardia in Structural Heart Disease

Study Overview
=================
Brief Summary
-----------------
A multicentre trial on clinical effects of radiosurgical ablation of ventricular tachycardia (VT).

Detailed Description
-----------------
Patients with previously failed conventional RF catheter ablation will be randomized to radiosurgery (active treatment group) or repeated catheter ablation (control treatment group). Details on inclusion and exclusion criteria are provided below. Randomization Eligible patients will be assigned to 2 treatment arms - radiosurgery (active arm) or repeated catheter ablation (control arm) in 1:1 fashion by covariate-adaptive randomization algorithm considering age, gender, etiology of structural heart disease (SHD), left ventricular (LV) ejection fraction, and serum B-type natriuretic peptide (NT-proBNP) level.

Official Title
-----------------
STereotactic Ablative Radiosurgery of Recurrent Ventricular Tachycardia in Structural Heart Disease

Conditions
-----------------
Ventricular Tachycardia

Intervention / Treatment
-----------------
* Procedure: Radiosurgery
* Procedure: Repeated catheter ablation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with structural heart disease (SHD) of any etiology (ischemic, non-ischemic, congenital corrected or uncorrected) Implanted implantable cardioverter-defibrillator (ICD) or cardiac resynchronization therapy-defibrillator (CRT-D) Prior ≥1 catheter ablation procedure for VT due to SHD of them the last one performed in the expert center and employed: 3.1 all meaningful mapping/ablation approaches (endocardial/epicardial access to left / right ventricular substrate as possible or appropriate) 3.2 precise electroanatomical mapping of the arrhythmogenic substrate in anticipation of future radiosurgery 3.3 additional mapping of structures used for precise image integration (aortic arch, left main ostium, right ventricular endocardial surface) VT recurrence after the last catheter ablation fulfilling all criteria as follows: 4.1 clinically relevant and requiring further intervention 4.2 compatible with the previously characterized arrhythmogenic substrate 4.3 occurred on stable antiarrhythmic medication (mostly amiodarone) unless contraindicated 4.4 reversible cause excluded Signed an Institutional Review Board (IRB)-approved written informed consent Exclusion Criteria: Age < 20 years Acute coronary syndrome or recent percutaneous coronary intervention or cardiac surgery (< 3 months) Primary electrical disease (channelopathy) Pregnancy or breastfeeding Chronic heart failure with New York Heart Association (NYHA) Class IV Serious comorbidities with presumed life expectancy less than one year Significant peripheral artery disease precluding retrograde aortic mapping

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: The study subjects will be randomized into one of the two study arms.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Radiosurgery<br>Eligible patients will be assigned to 2 treatment arms - radiosurgery (active arm) or repeated catheter ablation (control arm) in 1:1 fashion by covariate-adaptive randomization algorithm considering age, gender, etiology of SHD, LV ejection fraction, and serum NT-proBNP level. | Procedure: Radiosurgery<br>* The study subjects randomized in this study arm will undergo a radiosurgery procedure.<br>|
| Active Comparator: Repeated catheter ablation<br>Eligible patients will be assigned to 2 treatment arms - radiosurgery (active arm) or repeated catheter ablation (control arm) in 1:1 fashion by covariate-adaptive randomization algorithm considering age, gender, etiology of SHD, LV ejection fraction, and serum NT-proBNP level. | Procedure: Repeated catheter ablation<br>* The study subjects randomized in this study arm will undergo repeated catheter ablation.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrence of sustained VT after 3-month blanking period | Recurrence of sustained VT after 3-month blanking period will be assessed. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| VT burden according to implantable device | Number of sustained VT burden in three 3-month intervals after radiosurgery will be assessed. | 3 months | 
| Non-inducibility of VT at 6 months | TRUE/FALSE - Pacing protocol will be using 2 basic cycle length drives (600 and 400 ms) and 1-3 extrastimuli with coupling intervals decremented by 10 ms up to the refractoriness or 200 ms. | 6 months | 
| Recurrence of sustained VT excluding antitachycardia-pacing (ATP)-treated episodes | Recurrence of sustained VT excluding ATP-treated episodes will be assessed. | 24 months | 
| Electric storm recurrence | The recurrence of electric storm will be observed. | 24 months | 
| Cardiovascular hospitalization | The number of hospitalisations due to cardiovascular indications will be observed. | 24 months | 
| All-cause death | The all-cause death will be observed. | 24 months | 
| Change in quality of life: EQ-5D | Change in quality of life will be observed using the standardised EQ-5D (5-dimension) questionnaire. EQ-5D is a standardised instrument in the form of a questionnaire developed by the EuroQol Group as a measure of health-related quality of life that can be used in a wide range of health conditions and treatments. The quality of life is assessed in five dimensions, with three levels in each dimension. The higher score the patient achieves, the better the quality of life. | 24 months | 
| Change in echocardiographic indices | Left vetricle ejection fraction (%) will be observed. | 24 months | 
| Rate of major procedure-related complications (control arm) | The rate of major procedure-related complications will be observed among the study subjects enrolled to the control arm of the study, according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0). | 24 months | 
| Rate of acute post-radiation complications (intervention arm) | The rate of acute post-radiation complications will be observed among the study subjects enrolled to the intervention arm of the study, according to the Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) | 24 months | 
| Extent of scar | The extent of scar will be assessed 6 months after radiosurgery, based on invasive electroanatomical mapping. | 6 months | 
| Rate of late radiation-induced events | The rate of late radiation-induced events will be assessed according to CTCAE 5.0 in each cohort of isodose line level, specifically, rate of radiation myocarditis, pericarditis, and pneumonitis. | 24 months | 
| Radiation dose | The radiation dose will be observed for each interventional procedure, CT imaging and radiosurgery, together with the cumulative dose. | 24 months | 
| Need of antiemetic drugs | The need of antiemetic drugs will be assessed in all study subjects. | 24 months | 
| Dynamics of serum troponin level | The dynamics of serum troponin level will be observed in all study subjects. | 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Structural Heart Disease, Ventricular Tachycardia, Substrate Ablation, Stereotactic Radiosurgery, Functional Radiosurgery, 4D navigation