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

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
21

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • 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

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

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

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

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

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
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

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
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

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Azienda Provinciale per i Servizi Sanitari, Provincia Autonoma di Trento

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
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)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
February 1, 2025

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
February 1, 2030

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
February 1, 2030

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
January 7, 2025

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 7, 2025

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
March 25, 2025

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
March 25, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
January 23, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant 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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