Ventricular ArrhythmiaTOVELNCT06769451
Proton Radiosurgery for the Treatment of Malignant Ventricular Tachyarrhythmias
A study testing Stereotactic Arrhythmia Radioablation (STAR) with Proton Therapy in people with Ventricular Arrhythmia and Ventricular Tachycardia (V-Tach), run by Azienda Sanitaria Universitaria Integrata del Trentino at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Ventricular Arrhythmia, Ventricular Tachycardia (V-Tach)
- What is being tested?
- Stereotactic Arrhythmia Radioablation (STAR) with Proton Therapy
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 1 siteItaly
- Study dates
- Feb 2025to Feb 2030
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- age ≥ 40 years
- carrier of ICD/CRT-D or S-ICD
- 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);
- 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.
- Left ventricular ejection fraction ≥ 20%.
Who cannot join
- inability to express informed consent
- previous thoracic radiotherapy (RT) with cardiac involvement
- active myocardial ischemia
- recent cardiac revascularization (< 120 days)
- hemodynamic instability (cardiogenic shock, NYHA class IV)
- contraindication to radiosurgery (e.g., due to artifacts or other technical reasons)
Show all 10Show fewer
- lack of patient cooperation in pre-procedural investigations
- ICD malfunction
- severe comorbidity with prognosis < 12 months
- pregnancy
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site
Cardiology Rovereto and Proton Therapy Trento, Azienda Provinciale per i Servizi Sanitari (APSS)
Trento, Italy, 38123
Maurizio Del Greco, M.D., +390464403312, maurizio.delgreco@apss.tn.it
Frank RH Lohr, M.D., +3904611953100, frank.lohr@apss.tn.it
About this study
Official title: 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.
- Being tested
- Stereotactic Arrhythmia Radioablation (STAR) with Proton Therapy
- Keywords
- Stereotactic arrhythmia radioablation (STAR), Malignant ventricular Tachycardia, Ventricular Tachycardia Storm, Radiotherapy, Proton Therapy
- Medical subject headings
- Tachycardia, Ventricular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Stereotactic Arrhythmia Radioablation (STAR) with Proton TherapyRadiation
STAR with a single dose of 25Gy(RBE) Proton Therapy
| Study group | Role | What they receive |
|---|---|---|
| Radiosurgical ablation of a tachyarrhytmogenic substrate with Proton Therapy | Experimental | 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. Receives: Radiation: Stereotactic Arrhythmia Radioablation (STAR) with Proton Therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity of STAR with a single dose of 25Gy(RBE) applied with Proton 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."
Measured: Recording of MAEs for the first 24 months after therapy
Secondary outcomes (1)
Efficacy of STAR with a single dose of 25Gy(RBE) applied with Proton 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.
Measured: Efficacy measures will be recorded for the first 24 months after therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Jan 2025
- Study startFeb 2025 (estimated)
- Primary completionFeb 2030 (estimated)
- Study completionFeb 2030 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Ventricular ArrhythmiaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 21 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Azienda Sanitaria Universitaria Integrata del Trentino
- Sponsor type
- University, hospital or other
- Collaborators
- Università degli Studi di Trento
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06769451
- Sponsor's protocol ID
- A757
- Acronym
- TOVEL
- Status last verified
- Dec 2024
- First submitted
- 7 Jan 2025
- Last updated
- 27 Jan 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 39177652Kovacs 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.
PubMed 38666444Sultan 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.
PubMed 38363995Widesott 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.
PubMed 32911373
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Radiosurgery With proTOns for the Treatment of VEntricular maLignant Tachyarrhytmias (TOVEL Study)
- ClinicalTrials.gov ID
- NCT06769451
- Acronym / sponsor ID
- TOVEL / A757
- Keywords
- Stereotactic arrhythmia radioablation (STAR), Malignant ventricular Tachycardia, Ventricular Tachycardia Storm, Radiotherapy, Proton Therapy
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 21 participants (estimated)
- Lead sponsor
- Azienda Sanitaria Universitaria Integrata del TrentinoUniversity, hospital or other
- Collaborators
- Università degli Studi di Trento
- Study start
- Feb 2025 (estimated)
- Primary completion
- Feb 2030 (estimated)
- Study completion
- Feb 2030 (estimated)
- First posted
- 10 Jan 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Radiosurgical ablation of a tachyarrhytmogenic substrate with Proton Therapy | Experimental | Radiation: Stereotactic Arrhythmia Radioablation (STAR) with Proton TherapyAblation 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. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- age ≥ 40 years
- carrier of ICD/CRT-D or S-ICD
- episodes of ventricular tachycardia/ventricular fibrillation requiring defibrillator intervention (shock or ATP) which are:
- 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.
- Left ventricular ejection fraction ≥ 20%.
Key exclusion criteria (10 listed)
- inability to express informed consent
- previous thoracic radiotherapy (RT) with cardiac involvement
- active myocardial ischemia
- recent cardiac revascularization (< 120 days)
- hemodynamic instability (cardiogenic shock, NYHA class IV)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Stereotactic Arrhythmia Radioablation (STAR) with Proton TherapySTAR with a single dose of 25Gy(RBE) Proton Therapy | Radiation | Radiosurgical ablation of a tachyarrhytmogenic substrate with Proton Therapy |
Primary outcome
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."
1 secondary outcome
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2025.
- Background: PubMed 39177652Zeppenfeld 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.
- Background: PubMed 38666444Kovacs 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.
- Background: PubMed 38363995Sultan 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.
- Background: PubMed 32911373Widesott 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Stereotactic Arrhythmia Radioablation (STAR) with Proton Therapy in people with Ventricular Arrhythmia and Ventricular Tachycardia (V-Tach), run by Azienda Sanitaria Universitaria Integrata del Trentino at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 27 Jan 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Maurizio Del Greco, M.D. (+390464403312, maurizio.delgreco@apss.tn.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06769451, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 27 Jan 2025.