Dose Escalation for SBRT of Recurrent VT Ventricular Tachyarrhythmia - a Single Center, Phase II Clinical Trial

Study Overview
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Brief Summary
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The objective of this study is to demonstrate that higher radiation doses are necessary to induce transmural scar formation which is currently assumed to be the underlying mechanism of successful long-term efficacy of VT treatment and therefore dose-escalation will lead to a significantly reduced long-term VT recurrence rate compared to the currently applied single dose of 25 Gy.

Official Title
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Dose Escalation for Stereotactic Cardiac Radiation Therapy of Recurrent Ventricular Tachyarrhythmia - a Single Center, Phase II Clinical Trial

Conditions
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Ventricular Tachycardia

Intervention / Treatment
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* Device: Dose escalating stereotactic arrhythmia radioablation to treat ventricular tachycardia (VT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients with structural heart disease, in particular ischemic and non-ischemic cardiomyopathy: Implanted ICD and/or CRT-D. Prior ≥1 failed catheter ablation (with endocardial ± epicardial approach based on the substrate location and the ECG morphology of clinical VTs) procedure to control sustained monomorphic VT using currently recommended mapping and ablation techniques,2 or patients in whom ablation is not feasible. Reasons for lack of epicardial ablation and non-feasibility of catheter ablation must be specified. Sustained VT recurrence after catheter ablation on optimised antiarrhythmic medication. Age ≥18 years. IRB-approved, written informed consent must be provided Exclusion Criteria: Patients with only premature ventricular contractions. Patients with sustained VT/VF who demonstrate: Acute myocardial infarction; Primary electrical disease (channelopathy); Reversible and treatable cause (e.g., drug-induced or intoxication) of VT that can be adequately addressed otherwise; A target that cannot be safely and precisely defined based on stereotactic radiotherapy accuracy requirements (e.g., anatomical interference from OARs, overlapping prior radiation therapy to the thoracic region); Pregnancy or breastfeeding; Inability to provide informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: The study is designed as a one arm, single-center dose escalation trial employing the i3+3 design.
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalating stereotactic arrhythmia radioablation to treat ventricular tachycardia (VT)<br> | Device: Dose escalating stereotactic arrhythmia radioablation to treat ventricular tachycardia (VT)<br>* Dose escalating stereotactic arrhythmia radioablation to treat ventricular tachycardia (VT) refractory to conventional antiarrhythmic and catheter ablation-based therapy. First patients will be treated with a dose from 25 Gy prescribed to the 65-90% target volume encompassing isodose escalating to a maximum of 32.5 Gy prescribed to the 65-90% isodose.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| safety measured by registered radiation associated adverse events up to 90 days | safety measured by registered radiation associated adverse events | up to 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Radiation associated serious adverse event (at least grade 4 or 5 according to CTCAE v5) |  | As assessed at 90 days |