Proton Radiosurgery for the Treatment of Malignant Ventricular Tachyarrhythmias (TOVEL)

January 23, 2025 updated by: Azienda Provinciale per i Servizi Sanitari, Provincia Autonoma di Trento

Radiosurgery with ProTOns for the Treatment of VEntricular MaLignant Tachyarrhytmias (TOVEL Study)

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.

Study Overview

Status

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

21

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Italy
      • Trento, Italy, 38123
        • Cardiology Rovereto and Proton Therapy Trento, Azienda Provinciale per i Servizi Sanitari (APSS)
        • Contact:
        • Contact:
        • Contact:
          • Maurizio Del Greco, M.D.

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Radiosurgical ablation of a tachyarrhytmogenic substrate with Proton Therapy
Ablation of the arrhythmogenic substrate with a single dose of 25Gy(RBE) with Proton Therapy after pretreatment diagnostics with CT, MR and electrophysiology for the definition of the arrhytmogenic substrate. Follow-up for 24 months after treatment.
Radiation: Stereotactic Arrhythmia Radioablation (STAR) with Proton Therapy
STAR with a single dose of 25Gy(RBE) Proton Therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Toxicity of STAR with a single dose of 25Gy(RBE) applied with Proton Therapy
Time Frame: Recording of MAEs for the first 24 months after therapy
The primary endpoint will be the assessment of the toxicity of proton therapy and will be evaluated in the acute phase (during the first 30 days of the procedure) and at 3, 6, 12, 18, and 24 months. The incidence of Major Adverse Events (MAEs) related to, or presumed to be related, to proton therapy ablation will be assessed as percentage of patients with events compared to the total enrolled. The definition of MAEs (for the primary endpoint of the study) is identical to that of SAEs (as defined for reporting under Good Clinical Practice (GCP)) and can be found in the section "Serious Adverse Events (SAEs) / Major Adverse Events (MAEs) of the study protocol."
Recording of MAEs for the first 24 months after therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Efficacy of STAR with a single dose of 25Gy(RBE) applied with Proton Therapy
Time Frame: Efficacy measures will be recorded for the first 24 months after therapy

The main secondary endpoint will be the efficacy endpoint, which will involve evaluating the procedural effectiveness of therapy at 3, 6 and 12, 18 and 24 months and is the percentage reduction in VT/VF (Ventricular Tachycardia/Ventricular Fibrillation) episodes occurring after the 2-month "blanking period," compared with the period before the proton ablation procedure (6 months).

VT episodes will be classified as follows:

  • VT episodes > 30 s, regardless of ICD intervention
  • ICD interventions on VT episodes by "antitachycardia pacing" (without shock delivery)
  • ICD interventions with appropriate DC shocks
  • Number of subjects with ≥ 50% reduction in the number of ICD treatments for VT (shock or antitachycardia pacing, ATP) comparing the 6-month period before proton therapy with the 8 months after proton therapy (excluding the 2-month blanking period after Proton Therapy).

In addition, a series of other secondary toxicity and efficacy endpoints will be evaluated.
Efficacy measures will be recorded for the first 24 months after therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Azienda Provinciale per i Servizi Sanitari, Provincia Autonoma di Trento

Collaborators

Università degli Studi di Trento

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

February 1, 2025

Primary Completion (Estimated)

February 1, 2030

Study Completion (Estimated)

February 1, 2030

Study Registration Dates

First Submitted

January 7, 2025

First Submitted That Met QC Criteria

January 7, 2025

First Posted (Actual)

March 25, 2025

Study Record Updates

Last Update Posted (Actual)

March 25, 2025

Last Update Submitted That Met QC Criteria

January 23, 2025

Last Verified

December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • A757

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

UNDECIDED

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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