Stereotactic Management of Arrhythmia - Radiosurgery in Treatment of Ventricular Tachycardia

Study Overview
=================
Brief Summary
-----------------
Prospective single-arm study investigating the safety of non-invasive cardiac radiosurgery for the treatment of ventricular tachycardia (VT).

Detailed Description
-----------------
The standard of care for the treatment of Ventricular Tachycardia (VT) comprises of pharmacotherapy, ICD implantation and electrophysiology-guided catheter ablation. The treatment, however, is associated with a relatively high risk of VT recurrence. Given the limited therapeutic options and significant impact on patients quality of life, non-invasive cardiac radiosurgery has been recently gaining popularity in scientific literature as a viable alternative to salvage catheter ablations. Considering the scarcity of data from prospective trials and concern about the safety of the treatment method, this trial seeks to determine whether Stereotactic Management of Arrhythmia - Radiosurgery in Treatment of Ventricular Tachycardia (SMART-VT) meets the expected safety requirements for clinical use.

Official Title
-----------------
Stereotactic Management of Arrhythmia - Radiosurgery in Treatment of Ventricular Tachycardia

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

Intervention / Treatment
-----------------
* Radiation: Cardiac Radiosurgery


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with structural heart disease and implantable cardioverter defibrillator (ICD) Clinically significant arrhythmia with at least 3 VT episodes per month despite adequate pharmacological treatment. At least one episode of monomorphic VT registered in electrophysiological examination. Recurrent VT despite at least one prior catheter ablation and adequate pharmacotherapy OR contraindications to catheter ablation and/or pharmacotherapy (i.e., patient with medically contraindicated catheter ablation is obliged to undergo only pharmacotherapy prior to study enrollment). Patient must be able to understand and be willing to sign a written informed consent document. Exclusion Criteria: Heart failure requiring inotropic treatment or mechanical assistance Arrhythmia due to cardiac channelopathy Reversible source of arrhythmia NYHA (New York Heart Association) stage IV hearth failure Hearth infarction or cardiac surgery in last 3 months Life expectancy <6 months Polymorphic VT Pregnancy Prior radiotherapy to the thoracic region (relative contraindication) Failure to induce VT during electrophysiological examination

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

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

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

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

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Cardiac Radiosurgery<br>Patients with ventricular tachycardia will undergo a non-invasive cardiac radiosurgery using one fraction of 25 Gy to the arrhythmia substrate, as determined by the electrophysiological cardiac mapping. | Radiation: Cardiac Radiosurgery<br>* Non-invasive delivery of ablative radiotherapy dose to the arrhythmia substrate.<br>* Other names: Stereotactic Arrhythmia Radioablation (STAR);|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute toxicity evaluated using CTCAE v5.0 scale | The study aims to demonstrate the safety of the treatment method defined as 3-month observation without Grade III or higher adverse events in at least 6 out of 7 patients (1st stage), and in total in at least 9 out of 11 patients (2nd stage) with an interim safety analysis after obtaining data on primary outcome in first 7 patients. | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy of the treatment | Reduction of VT burden, ICD shocks and improvement in life quality as described by SF-36 (The Short Form Health Survey) v2 questionnaire. f eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability. | 24 months | 
| Biochemical markers of cardiac injury | Intensity and dynamics of changes in cardiac-related biochemical indices after treatment, like troponin, cardiac creatine kinase (MB-CK) concentration and N-terminal prohormone of brain natriuretic peptide (NT-proBNP) to assess the early cardiac muscle damage and changes in severity of congestive heart failure. | 24 months | 
| Late toxicity and mortality | Assessment of late toxicity including occurrence of cardiac-related hospitalizations and death. | 24 months | 
| Anti-arrhythmic drugs uptake | Changes in the anti-arrhythmic medications over time after treatment. | 24 months | 
| Cardiac injury | Assessment of the post-treatment cardiac injury including left ventricular ejection fraction, echocardiography and morphological changes in imaging studies. | 24 months | 
| Target volume delineation | Correlation of electrophysiological mapping with the results of additional cardiac imaging methods (MR, PET) - only in applicable patients (optional diagnostic methods) | 24 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Ventricular Tachycardia, Ablation, Noninvasive, Stereotactic Body Radiation Therapy, Radiosurgery, Substrate Ablation