Clinical trial NCT05765175: Cardiac RADIoablation Versus Repeat Catheter Ablation: a Pivotal Randomized Clinical Trial Evaluating Safety and Efficacy for Patients With High-risk Refractory Ventricular Tachycardia (RADIATE-VT)
Official title: Cardiac RADIoablation Versus Repeat Catheter Ablation: a Pivotal Randomized Clinical Trial Evaluating Safety and Efficacy for Patients With High-risk Refractory Ventricular Tachycardia
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Tachycardia, Ventricular
Keywords: Cardiac radioablation
Ventricular tachycardia
Catheter ablation
Refractory ventricular tachycardia
High risk
SBRT
Lead sponsor: Varian, a Siemens Healthineers Company
Sponsor class: INDUSTRY
First posted: 2023-03-13
Enrollment: 380
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: The Varian CRA trial is a multicenter, international, pivotal, 2-arm randomized controlled trial (RCT). Subjects will be randomized 1:1 to CRA or repeat CA. Randomization will be stratified by (1) enrolling institution and (2) NYHA class I/II vs. III/IV. Blinding will not be used in this trial, as the different interventions cannot be blinded.
Primary purpose: TREATMENT

Brief summary: RADIATE-VT is a pivotal, multicenter, randomized trial comparing safety and efficacy between cardiac radioablation (CRA) using the Varian CRA System and repeat catheter ablation (CA), for patients with high-risk refractory ventricular tachycardia (VT) who have experienced VT recurrence after CA and are candidates for additional CA.


Eligibility criteria: Inclusion Criteria:

1. High-risk refractory VT, defined as:

   1. Ischemic and/or nonischemic cardiomyopathy, and
   2. Recurrent sustained monomorphic VT, defined as at least one of the following below, documented by ICD interrogation or ECG in the prior 6 months, and having occurred after the last VT ablation:

      A: ≥3 episodes of monomorphic VT treated with anti-tachycardia pacing (ATP) at least one of which is symptomatic

      B: ≥1 appropriate ICD shock

      C: ≥3 episodes of sustained monomorphic VT within 24 hours treated with ICD shock or ATP

      D: sustained monomorphic VT below detection rate of ICD documented by ECG, and
   3. Left ventricular ejection fraction (LVEF) ≤49% and
   4. Previously underwent at least one standard of care CA for VT.
2. Presence of a clinical indication for a repeat CA procedure for scar-mediated VT in the judgement of the treating investigator.
3. Has failed amiodarone therapy or is intolerant to amiodarone:

   * Failed amiodarone therapy is defined as: appropriate ICD therapy or sustained monomorphic VT having occurred while the patient was taking amiodarone (minimum cumulative dose of 10 g).
   * Intolerant to amiodarone is defined as: previously tried or taken amiodarone but stopped due to medication related side effects or toxicities.
4. Deemed to be medically and technically a candidate for further CA by the electrophysiologist investigator.
5. Presence of an ICD.
6. At least 18 years of age (or meets local age of majority).
7. Ability to understand and willingness to sign an IRB approved written informed consent document.

Exclusion Criteria:

1. Contraindication to a CA procedure for VT (e.g., presence of mobile LV thrombus, active systemic infection, active ischemic or other reversible causes of VT).
2. Patients with expected, right ventricular scar only.
3. Any prior radiation to the thorax region of the body.
4. Known medical conditions associated with higher risk of radiotherapy complications in the judgement of the radiation oncologist (i.e., active connective tissue disorders, interstitial lung disease, etc.) that would preclude safe delivery of CRA.
5. Current use of inotropes.
6. Presence of a left-ventricular assist device (LVAD).
7. Scheduled for LVAD or heart transplant procedures.
8. Presence of a systemic illness likely to limit survival to \< 1 year.
9. VT ablation procedure performed within the prior 2 weeks.
10. Polymorphic VT or ventricular fibrillation (VF) as the primary clinical heart rhythm, as indicated by 12-lead ECG and/or ICD interrogation.
11. \>3 distinct clinical monomorphic VT morphologies on ICD interrogation since the prior CA, or \>5 induced monomorphic VT morphologies during NIPS testing.
12. Incessant VT that is hemodynamically unstable.
13. Bundle branch reentry (BBR) VT.
14. Pregnant and/or breastfeeding. (Patient denial is sufficient for enrollment).
15. Patients of childbearing potential who:

    * are not on a medically effective means of birth control at the time of screening or do not start a medically effective means of birth control prior to randomization; or
    * do not agree to continue medically effective means of birth control until they have completed their assigned therapy; or
    * do not agree to be on a medically effective means of birth control if they are treated with CRA after their index CA procedure.
16. Patients enrolled in another clinical study the investigator believes to be in conflict with this clinical investigation.
17. Patients enrolled or planned to be enrolled in another cardiac radioablation clinical study or registry.
18. Patients with any other medical condition or laboratory value that would, at the discretion of the investigator, preclude the patient from participation in this clinical investigation.

Primary outcomes:
measure: Co-primary safety endpoint: freedom from treatment-attributed (i.e., probably or definitely related) serious adverse events (SAEs)
timeFrame: Treatment through 12 months post-treatment
measure: Co-primary efficacy endpoint: Freedom from death, and appropriate ICD shock, and VT storm.
timeFrame: Death will be counted from randomization through 12 months, and shock and storm will be counted starting after a 30-day period immediately post-randomization and continuing through 12 months post randomization
Secondary outcomes:
measure: Change in quality of life at 6 weeks post treatment:
timeFrame: From baseline through 6 weeks post treatment
measure: VT burden reduction
timeFrame: From 6 months before randomization through to a 6 month period starting after a 30-day period immediately post-randomization
measure: Change in quality of life (Social Functioning) at 6 weeks post treatment
timeFrame: From baseline through 6 weeks post treatment
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: Hartford
country: United States
facility: Hartford Hospital
state: Connecticut
city: Boston
country: United States
facility: Brigham & Women's Hospital
state: Massachusetts
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Columbus
country: United States
facility: The Ohio State University
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center
state: Pennsylvania
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Medical Center
state: Tennessee
Study officials:
References: