Clinical trial NCT02919618: Phase I/II Study of EP-guided Noninvasive Cardiac Radioablation for Treatment of Ventricular Tachycardia
Official title: Phase I/II Study of EP-guided Noninvasive Cardiac Radioablation for Treatment of Ventricular Tachycardia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Ventricular Tachycardia
Cardiomyopathy
Premature Ventricular Contractions
Keywords: Ventricular Tachycardia
Ablation
Noninvasive
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
First posted: 2016-09-29
Enrollment: 19
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Noninvasive Cardiac Radioablation, all subjects
Primary purpose: TREATMENT

Brief summary: Phase I/II Study of EP-guided Noninvasive Cardiac Radioablation (ENCORE) for Treatment of Ventricular Tachycardia

Detailed description: Patients with Ventricular Tachycardia (VT) who have failed standard therapy (medicines, invasive catheter ablation) have limited options, with one-year survival below 20%. Preclinical data demonstrate that single fraction stereotactic body radiotherapy (SBRT) to discrete portions of the heart is feasible and may result in a reduction or elimination of VT. The efficacy may be further improved when guided by cardiac electrophysiologic (EP) testing. In total, the mapping and ablation proposed for this EP-guided Noninvasive Cardiac Radioablation (ENCORE) is a rapid and totally non-invasive method. Overall safety and early efficacy of ENCORE have not been rigorously studied in a prospective trial to-date. The purpose of this phase I/II study is to demonstrate the short-term safety and preliminary efficacy of ENCORE for patients with life-threatening, treatment-refractory VT.

Eligibility criteria: Inclusion Criteria:

1. DOCUMENTED VT:

   1. Patient must have documented sustained monomorphic ventricular tachycardia as documented on either a 12-lead ECG or intracardiac ICD interrogation

      - OR-
   2. Monomorphic PVCs documented on a 12-lead ECG.
2. ANTIARRHYTHMIC MEDICATION: Patient must have failed or become intolerant to at least one antiarrhythmic medication (amiodarone, sotalol, or mexiletine).

   -AND-
3. CATHETER ABLATION: Patient must have failed at least one invasive catheter ablation procedure, or have a contraindication to a catheter ablation procedure (e.g., LV thrombus, severe pulmonary disease), or have VT thought to arise from a protected location (e.g., epicardial VT with history of previous cardiac surgery).
4. MINIMUM VT BURDEN: Patient must have either:

   1. At least 3 VT episodes (sustained VT, ICD ATP or ICD shock) over previous 6 months prior to enrollment -OR-
   2. \>20% PVC burden with a cardiomyopathy (LVEF\<50%)
5. Patient must be deemed medically fit for stereotactic body radiation therapy by the treating physician.
6. Patient must be \> 18 years old.
7. Patient must be able to understand and be willing to sign an IRB approved written informed consent document.

   -

Exclusion Criteria:

1. Patient must not have past history of radiotherapy within the projected treatment field.
2. Advanced symptomatic heart failure as defined as NYHA Class IV heart failure (inotrope dependent and/or current left-ventricular assist device (LVAD))
3. Polymorphic VT or ventricular fibrillation (VF) as a clinical heart rhythm (as determined by 12-lead ECG and/or ICD interrogation).
4. More than 3 distinct clinical VT morphologies observed (ECG or ICD interrogation or invasive EP study) OR more than 5 distinct induced VT morphologies during ECGI testing.
5. Advanced myocardial scar substrate that would require stereotactic delivery to a target volume deemed unsafe by the treating physician.
6. Unlikely to live 12 months, in the absence of VT, as best based on clinical judgment by the treating and enrolling physicians.
7. Patient must not be pregnant and/or breastfeeding and must have a negative pregnancy test within 14 days of study entry.

   -

Primary outcomes:
measure: Number of Serious Adverse Events
timeFrame: < or = 90 days
measure: Number of Participants With Reduction in Ventricular Tachycardia (VT) Burden
timeFrame: 12 months (6mo prior to and 6mo post SBRT)
Secondary outcomes:
measure: Overall Survival
timeFrame: 12 months
measure: Number of Adverse Events That Are Possibly/Probably/Definitely Related to Study Treatment
timeFrame: 90 days to 12 months
measure: Health Related Quality of Life (HRQOL)
timeFrame: 6 week, 6 month, 12 month
measure: Number of Participants With a 50% Reduction in Ventricular Tachycardia (VT) Burden
timeFrame: 6 months
measure: Number of Participants With a 95% Reduction in Ventricular Tachycardia (VT) Burden
timeFrame: 6 months
measure: Number of Participants With Reduction in ICD Shocks and LVEF Improvement
timeFrame: 6 months
measure: Number of Participants With Reduction in Ventricular Tachycardia (VT) Therapies Between 6 and 12 Months
timeFrame: 12 months
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Phillip Cuculich, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Robinson CG, Samson PP, Moore KMS, Hugo GD, Knutson N, Mutic S, Goddu SM, Lang A, Cooper DH, Faddis M, Noheria A, Smith TW, Woodard PK, Gropler RJ, Hallahan DE, Rudy Y, Cuculich PS. Phase I/II Trial of Electrophysiology-Guided Noninvasive Cardiac Radioablation for Ventricular Tachycardia. Circulation. 2019 Jan 15;139(3):313-321. doi: 10.1161/CIRCULATIONAHA.118.038261.