Trial in Arrhythmia Radioablation for Ventricular Tachycardia: Single Fraction vs Three Fractions

Official title

Dose De-escalation Randomized Phase I/II Trial in Arrhythmia Radioablation for Ventricular Tachycardia: Single Fraction vs Three Fractions

Overview

This is a research study that aims to understand if giving a lower dose of treatment all at once is as effective and safe as dividing it into three smaller doses for patients with a heart condition called refractory ventricular tachycardia (VT). These patients have not exhibited positive responses to conventional medications or procedures. This study aims to explore whether an alternative approach could yield more beneficial outcomes.

Detailed description

Ventricular tachycardia (VT) is a life-threatening heart rhythm disorder that arises from areas of diseased tissue in the heart. Treatment of VT can involve anti-arrhythmic drugs and catheter-based ablations. Unfortunately, despite multiple antiarrhythmic drugs, as well as the catheter-based ablation procedures, VT continues to persist in your case. At this point in time, The investigators believe that stereotactic body radiotherapy (SBRT) remains the only possible option to potentially treat VT. The investigators hypothesize that by administering SBRT at different dose levels and fractionation may achieve a better therapeutic ratio, defined as comparable efficacy with less risk of toxicity due to lower dose exposure to the normal tissue, including the heart vasculature, in patients when compared to VT patients who receive a dose of 25Gy in a single fraction which is the current treatment option.

This is a randomized dose de-escalation trial where the patients will be randomized in in one of the two experimental arms, receiving 1 single fraction OR 3 daily consecutive fractions of RT, and will be treated into a prespecified dose level group, based on the study development. The study includes three de-escalated consecutive dose level groups for each of two randomized treatment arms and there will be 3 patients per group and each group will receive a particular radiation treatment either as single treatments or three treatments.

The purpose of this treatment is to safely reduce episodes of VT.

Interventions

• Radiation Radiation Therapy
  Group 1 (3 participants) - will receive a dose of 20 Gy ("Gray", a measurement of radiation) in a single study intervention (one study intervention day)
• Radiation Radiation Therapy
  Group 2 (3 participants) - will receive a dose of 15 Gy in a single study intervention (one study intervention day)
• Radiation Radiation Therapy
  Group 3 (3 participants) - will receive a dose of 10 Gy in a single study intervention (one study intervention day)
• Radiation Radiation Therapy
  Group 1 (3 participants) - will receive a dose of 12 Gy given over 3 days (Days 1, 2 and 3). (Total radiation dose = 36Gy)
• Radiation Radiation Therapy
  Group 2 (3 participants) - will receive a dose of 10 Gy given over 3 days (Days 1, 2 and 3). (Total radiation dose = 30Gy)
• Radiation Radiation Therapy
  Group 3 (3 participants) - will receive a dose of 8 Gy given over 3 days (Days 1, 2 and 3). (Total radiation dose = 24Gy)

Primary outcome measures

• Efficacy as measured by number of subjects with a reduction ≥ 60% (tracked by ICD recordings) ventricular tachycardia (VT) episodes [Time frame: 6 months before treatment]
• Efficacy as measured by number of subjects with a reduction ≥ 60% (tracked by ICD recordings) ventricular tachycardia (VT) episodes [Time frame: 6 weeks post treatment]
• Number of treatment-related serious adverse events (SAEs) [Time frame: 6 weeks post treatment]

Secondary outcome measures (12)

• Number of ventricular tachycardia (VT) episodes [Time frame: 3 months post]
• Number of ventricular tachycardia (VT) episodes [Time frame: 6 months post]
• Number of ventricular tachycardia (VT) episodes [Time frame: 12 months]
• Number of subacute treatment side-effects [Time frame: 3 months post]
• Number of subacute treatment side-effects [Time frame: 6 months post]
• Number of late Adverse events [Time frame: 1 year post]
• Number of late Adverse events [Time frame: 2 year post]
• Overall survival [Time frame: 1 year post]
• Overall survival [Time frame: 2 year post]
• Recurrence free survival [Time frame: 3 months post]
• Recurrence free survival [Time frame: 6 months post]
• Recurrence free survival [Time frame: 12 months post]

Eligibility criteria

Inclusion criteria

• Age ≥ 18 years
• Structural heart disease:

• Ischemic cardiomyopathy
• Non-ischemic cardiomyopathy
• Hypertrophic cardiomyopathy
• Refractory VT severity:

• VT leading to ICD shock with minimum 3 episodes in any 3-month period without reversible cause;
• Failed or intolerant to antiarrhythmic drug therapy (either amiodarone or ≥ 2 AADs) AND failed ablation (CA)
• OR ablation (CA) contraindicated
• Ability to understand study protocol and to write informed consent
• Willing to comply with specified pre-, post- and follow-up testing, evaluations and requirements
• Expected to remain available for at least 36 months after enrollment

Exclusion criteria

• Age < 18 years
• Pregnancy
• Prior chest radiation therapy

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

United States · 1 center

• Weill Cornell Medicine — New York

Identifiers

NCT: NCT06743789 · 23-09026474

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗