Clinical trial NCT06769451: Proton Radiosurgery for the Treatment of Malignant Ventricular Tachyarrhythmias
Official title: Radiosurgery With proTOns for the Treatment of VEntricular maLignant Tachyarrhytmias (TOVEL Study)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Ventricular Arrhythmia
Ventricular Tachycardia (V-Tach)
Keywords: Stereotactic arrhythmia radioablation (STAR)
Malignant ventricular Tachycardia
Ventricular Tachycardia Storm
Radiotherapy
Proton Therapy
Lead sponsor: Azienda Provinciale per i Servizi Sanitari, Provincia Autonoma di Trento
Sponsor class: OTHER
Collaborators: name: Università degli Studi di Trento
First posted: 2025-01-10
Enrollment: 21
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: Ventricular arrhythmias (VAs) are the leading cause of sudden cardiac death (SCD) worldwide. The implantable defibrillator (ICD) increases survival in patients at risk of VA, with data of superiority to antiarrhythmic drugs. Nevertheless, the ICD cannot prevent VAs, and shocks delivered by the device (appropriate and inappropriate) negatively impact patients' quality of life. Transcatheter ablation (TCA) is the percutaneous therapy that can eliminate VAs and prevent any recurrence. TCA is the state of the art for the treatment of drug-unresponsive VAs in patients with structural heart disease, but the prevalence of recurrence remains high (between 30% and 60%). For these reasons, several reports have recently appeared in the literature proposing a new solution for the treatment of VAs in which the use of external-beam body radiotherapy with stereotactic-radiosurgical technique (SBRT) is described. SBRT represents a rapid, noninvasive approach based on the delivery of high radiation doses of photons (25 Gy in a single fraction) to a precise location in cardiac tissue.

SBRT has entered the latest 2022 European Society of Cardiology (ESC) guidelines on VAs as a "bailout therapy". Based on preliminary data in the oncology setting, proton therapy could allow further optimization of compliance of these therapeutic doses by preserving even more of the healthy heart part and thus reducing the cardiopulmonary toxicity of radiotherapy outside the ablation target.

The investigators therefore propose an experimental (prospective interventional) study to evaluate the toxicity (primary endpoint) and efficacy (secondary endpoint) of proton radiosurgery for the treatment of VA with an enrollment of 21 patients. The primary endpoint is to evaluate the toxicity of proton radiotherapy in the acute phase (during the first 30 days of the procedure) and at 3, 6 and 12 months. A crucial part of the protocol will be the proper definition of the target to be irradiated, which will require the integration of different non-invasive cardiac imaging methodologies such as CT (Computed Tomography), MRI (Magnetic Resonance Imaging) and PET (Positron Emission Tomography), coupled with invasive and/or "non-invasive" body surface mapping with multi-electrode electrocardiogram (ECG) so as to obtain a "cardiac image" in which the myocardial scar and the arrhythmogenic region are fused.


Eligibility criteria: Inclusion Criteria:

1. age ≥ 40 years
2. carrier of ICD/CRT-D or S-ICD
3. episodes of ventricular tachycardia/ventricular fibrillation requiring defibrillator intervention (shock or ATP) which are:

   * refractory to maximal drug therapy;
   * recurrent (at least 3 episodes in the previous 6 months);
4. patients with contraindications to a conventional ablative strategy, in relation to the high risk associated with the procedure due to the severity of the heart disease and/or the presence of comorbidities or patients who have already undergone ablation, in the presence of an arrhythmogenic substrate refractory to or unsuitable for an interventional approach or patients who refuse transcatheter ablative attempts due to high intraoperative risk in relation to the patient's characteristics.
5. Left ventricular ejection fraction ≥ 20%.

Exclusion Criteria:

1. inability to express informed consent
2. previous thoracic radiotherapy (RT) with cardiac involvement
3. active myocardial ischemia
4. recent cardiac revascularization (\< 120 days)
5. hemodynamic instability (cardiogenic shock, NYHA class IV)
6. contraindication to radiosurgery (e.g., due to artifacts or other technical reasons)
7. lack of patient cooperation in pre-procedural investigations
8. ICD malfunction
9. severe comorbidity with prognosis \< 12 months
10. pregnancy

Primary outcomes:
measure: Toxicity of STAR with a single dose of 25Gy(RBE) applied with Proton Therapy
timeFrame: Recording of MAEs for the first 24 months after therapy
Secondary outcomes:
measure: Efficacy of STAR with a single dose of 25Gy(RBE) applied with Proton Therapy
timeFrame: Efficacy measures will be recorded for the first 24 months after therapy
Other outcomes:
Locations:
city: Trento
country: Italy
facility: Cardiology Rovereto and Proton Therapy Trento, Azienda Provinciale per i Servizi Sanitari (APSS)
Study officials:
References:
citation: Zeppenfeld K, Rademaker R, Al-Ahmad A, Carbucicchio C, De Chillou C, Cvek J, Ebert M, Ho G, Kautzner J, Lambiase P, Merino JL, Lloyd M, Misra S, Pruvot E, Sapp J, Schiappacasse L, Sramko M, Stevenson WG, Zei PC, Wichterle D, Chrispin J, Siklody CH, Neuwirth R, Pelargonio G, Reichlin T, Robinson C, Tondo C. Patient selection, ventricular tachycardia substrate delineation, and data transfer for stereotactic arrhythmia radioablation: a clinical consensus statement of the European Heart Rhythm Association of the European Society of Cardiology and the Heart Rhythm Society. Europace. 2025 Mar 28;27(4):euae214. doi: 10.1093/europace/euae214.
citation: Kovacs B, Lehmann HI, Manninger M, Saguner AM, Futyma P, Duncker D, Chun J. Stereotactic arrhythmia radioablation and its implications for modern cardiac electrophysiology: results of an EHRA survey. Europace. 2024 May 2;26(5):euae110. doi: 10.1093/europace/euae110.
citation: Sultan A, Futyma P, Metzner A, Anic A, Richter S, Roten L, Badertscher P, Conte G, Chun JKR. Management of ventricular tachycardias: insights on centre settings, procedural workflow, endpoints, and implementation of guidelines-results from an EHRA survey. Europace. 2024 Feb 1;26(2):euae030. doi: 10.1093/europace/euae030.
citation: Widesott L, Dionisi F, Fracchiolla F, Tommasino F, Centonze M, Amichetti M, Del Greco M. Proton or photon radiosurgery for cardiac ablation of ventricular tachycardia? Breath and ECG gated robust optimization. Phys Med. 2020 Oct;78:15-31. doi: 10.1016/j.ejmp.2020.08.021. Epub 2020 Sep 8.