Back to resultsPhase I/II Study of EP-guided Noninvasive Cardiac Radioablation for Treatment of Ventricular Tachycardia (ENCORE-VT)
Primary Purpose
Ventricular Tachycardia, Cardiomyopathy, Premature Ventricular Contractions
Status
Active
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
stereotactic body radiotherapy (SBRT)
Sponsored by
About this trial
This is an interventional treatment trial for Ventricular Tachycardia focused on measuring Ventricular Tachycardia, Ablation, Noninvasive
Eligibility Criteria
Inclusion Criteria:
DOCUMENTED VT:
Patient must have documented sustained monomorphic ventricular tachycardia as documented on either a 12-lead ECG or intracardiac ICD interrogation
- OR-
- Monomorphic PVCs documented on a 12-lead ECG.
ANTIARRHYTHMIC MEDICATION: Patient must have failed or become intolerant to at least one antiarrhythmic medication (amiodarone, sotalol, or mexiletine).
-AND-
- 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).
MINIMUM VT BURDEN: Patient must have either:
- At least 3 VT episodes (sustained VT, ICD ATP or ICD shock) over previous 6 months prior to enrollment -OR-
- >20% PVC burden with a cardiomyopathy (LVEF<50%)
- Patient must be deemed medically fit for stereotactic body radiation therapy by the treating physician.
- Patient must be > 18 years old.
Patient must be able to understand and be willing to sign an IRB approved written informed consent document.
-
Exclusion Criteria:
- Patient must not have past history of radiotherapy within the projected treatment field.
- Advanced symptomatic heart failure as defined as NYHA Class IV heart failure (inotrope dependent and/or current left-ventricular assist device (LVAD))
- Polymorphic VT or ventricular fibrillation (VF) as a clinical heart rhythm (as determined by 12-lead ECG and/or ICD interrogation).
- 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.
- Advanced myocardial scar substrate that would require stereotactic delivery to a target volume deemed unsafe by the treating physician.
- Unlikely to live 12 months, in the absence of VT, as best based on clinical judgment by the treating and enrolling physicians.
Patient must not be pregnant and/or breastfeeding and must have a negative pregnancy test within 14 days of study entry.
-
Sites / Locations
- Washington University School of Medicine
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
stereotactic body radiotherapy (SBRT)
Arm Description
Noninvasive SBRT will be delivered in a single fraction to a region of the heart determined by EP-guidance, using noninvasive electrical mapping combined with anatomic imaging.
Outcomes
Primary Outcome Measures
Number of Serious Adverse Events
Demonstrate acute (≤ 90 days) safety of noninvasive stereotactic cardiac ablation radiotherapy (ENCORE). The primary safety endpoint is defined by a ≤ 20% rate of serious adverse events (SAEs) using CTCAE v4.0 criteria that are possibly/probably/definitely related to study treatment, based on previously published data for expected invasive catheter-based VT-ablation procedures.
Number of Participants With Reduction in Ventricular Tachycardia (VT) Burden
Primary efficacy endpoint is defined by the number of subjects with a reduction in VT burden comparing the period six months before ENCORE treatment to the six months after ENCORE treatment as adjudicated by continuous ICD monitoring (number of ATP and ICD shocks and sustained (>30 second) nontreated slow VT). There will be a six-week "blanking period" after therapy to allow for ablation effect. For patients with PVC-induced cardiomyopathy, the primary efficacy will be any reduction in PVC burden based on ambulatory heart monitors.
Secondary Outcome Measures
Overall Survival
Determine six-month and twelve-month survival (overall mortality endpoint) after treatment with ENCORE.
Number of Adverse Events That Are Possibly/Probably/Definitely Related to Study Treatment
Toxicities that occur after treatment, but are not acutely ascribed to treatment that are possibly/probably/definitely related to study treatment, based on previously published data for expected invasive catheter-based VT-ablation procedures, using the CTCAE v4.0 criteria.
Health Related Quality of Life (HRQOL)
The 36-Item Short Form Survey (SF-36) is a set of generic, coherent, and easily administered quality of life measures that rely on patient self-reporting. The SF-36 evaluates 8 domains: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. Scale values for each domain range from 0 to 100 where the higher score defines a more favorable health state.
Number of Participants With a 50% Reduction in Ventricular Tachycardia (VT) Burden
Evaluate stricter efficacy endpoint of ENCORE treatment, as defined by number of patients who have had 50% reduction in any VT therapies (ATP or ICD shocks or sustained (>30sec) nontreated slow VT) after ENCORE treatment (6 months before vs. 6 months after treatment, with a 6 week blanking period immediately after treatment). For patients with PVC-induced cardiomyopathy, the stricter efficacy will be >50% reduction in PVC burden based on ambulatory heart monitors.
Number of Participants With a 95% Reduction in Ventricular Tachycardia (VT) Burden
Evaluate strictest efficacy endpoint of ENCORE treatment, as defined by number of patients who have had 95% reduction in any VT (ATP or ICD shocks or sustained (>30 sec) slow VT) after ENCORE treatment (6 months before vs. 6 months after treatment, with a 6 week blanking period immediately after treatment). For patients with PVC-induced cardiomyopathy, the strictest efficacy will be abolition of PVC burden (<1%) based on ambulatory heart monitors.
Number of Participants With Reduction in ICD Shocks and LVEF Improvement
Evaluate the most clinically useful efficacy endpoint of ENCORE treatment, namely, number of patients with reduction specifically in ICD shocks (6 months before vs. 6 months after treatment, with a 6 week blanking period immediately after treatment). For patients with PVC-induced cardiomyopathy, the most clinically useful efficacy will be improvement in cardiac function in the setting of any improvement in PVC burden.
Number of Participants With Reduction in Ventricular Tachycardia (VT) Therapies Between 6 and 12 Months
Evaluate longer-term durability endpoint of ENCORE treatment, as defined by number of patients with reduction in VT therapies (ATP or ICD shock or sustained (>30 sec) slow VT and ICD shock alone) during the early phase (treatment to 6 months, with 6 week blanking period) vs. the late phase (6 months to 1 year). For patients with PVC-induced cardiomyopathy, the longer-term durability efficacy will be persistence of any reduction in PVC burden based on ambulatory heart monitors during early phase vs. late phase.
Full Information
NCT ID
NCT02919618
First Posted
September 28, 2016
Last Updated
July 24, 2023
Sponsor
Washington University School of Medicine
1. Study Identification
Unique Protocol Identification Number
NCT02919618
Brief Title
Phase I/II Study of EP-guided Noninvasive Cardiac Radioablation for Treatment of Ventricular Tachycardia
Acronym
ENCORE-VT
Official Title
Phase I/II Study of EP-guided Noninvasive Cardiac Radioablation for Treatment of Ventricular Tachycardia
Study Type
Interventional
2. Study Status
Record Verification Date
July 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
July 2016 (Actual)
Primary Completion Date
July 23, 2018 (Actual)
Study Completion Date
January 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Washington University School of Medicine
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ventricular Tachycardia, Cardiomyopathy, Premature Ventricular Contractions
Keywords
Ventricular Tachycardia, Ablation, Noninvasive
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
19 (Actual)
8. Arms, Groups, and Interventions
Arm Title
stereotactic body radiotherapy (SBRT)
Arm Type
Experimental
Arm Description
Noninvasive SBRT will be delivered in a single fraction to a region of the heart determined by EP-guidance, using noninvasive electrical mapping combined with anatomic imaging.
Intervention Type
Radiation
Intervention Name(s)
stereotactic body radiotherapy (SBRT)
Intervention Description
(Cardiac ablative radiotherapy)
Primary Outcome Measure Information:
Title
Number of Serious Adverse Events
Description
Demonstrate acute (≤ 90 days) safety of noninvasive stereotactic cardiac ablation radiotherapy (ENCORE). The primary safety endpoint is defined by a ≤ 20% rate of serious adverse events (SAEs) using CTCAE v4.0 criteria that are possibly/probably/definitely related to study treatment, based on previously published data for expected invasive catheter-based VT-ablation procedures.
Time Frame
< or = 90 days
Title
Number of Participants With Reduction in Ventricular Tachycardia (VT) Burden
Description
Primary efficacy endpoint is defined by the number of subjects with a reduction in VT burden comparing the period six months before ENCORE treatment to the six months after ENCORE treatment as adjudicated by continuous ICD monitoring (number of ATP and ICD shocks and sustained (>30 second) nontreated slow VT). There will be a six-week "blanking period" after therapy to allow for ablation effect. For patients with PVC-induced cardiomyopathy, the primary efficacy will be any reduction in PVC burden based on ambulatory heart monitors.
Time Frame
12 months (6mo prior to and 6mo post SBRT)
Secondary Outcome Measure Information:
Title
Overall Survival
Description
Determine six-month and twelve-month survival (overall mortality endpoint) after treatment with ENCORE.
Time Frame
12 months
Title
Number of Adverse Events That Are Possibly/Probably/Definitely Related to Study Treatment
Description
Toxicities that occur after treatment, but are not acutely ascribed to treatment that are possibly/probably/definitely related to study treatment, based on previously published data for expected invasive catheter-based VT-ablation procedures, using the CTCAE v4.0 criteria.
Time Frame
90 days to 12 months
Title
Health Related Quality of Life (HRQOL)
Description
The 36-Item Short Form Survey (SF-36) is a set of generic, coherent, and easily administered quality of life measures that rely on patient self-reporting. The SF-36 evaluates 8 domains: physical functioning, bodily pain, role limitations due to physical health problems, role limitations due to personal or emotional problems, emotional well-being, social functioning, energy/fatigue, and general health perceptions. Scale values for each domain range from 0 to 100 where the higher score defines a more favorable health state.
Time Frame
6 week, 6 month, 12 month
Title
Number of Participants With a 50% Reduction in Ventricular Tachycardia (VT) Burden
Description
Evaluate stricter efficacy endpoint of ENCORE treatment, as defined by number of patients who have had 50% reduction in any VT therapies (ATP or ICD shocks or sustained (>30sec) nontreated slow VT) after ENCORE treatment (6 months before vs. 6 months after treatment, with a 6 week blanking period immediately after treatment). For patients with PVC-induced cardiomyopathy, the stricter efficacy will be >50% reduction in PVC burden based on ambulatory heart monitors.
Time Frame
6 months
Title
Number of Participants With a 95% Reduction in Ventricular Tachycardia (VT) Burden
Description
Evaluate strictest efficacy endpoint of ENCORE treatment, as defined by number of patients who have had 95% reduction in any VT (ATP or ICD shocks or sustained (>30 sec) slow VT) after ENCORE treatment (6 months before vs. 6 months after treatment, with a 6 week blanking period immediately after treatment). For patients with PVC-induced cardiomyopathy, the strictest efficacy will be abolition of PVC burden (<1%) based on ambulatory heart monitors.
Time Frame
6 months
Title
Number of Participants With Reduction in ICD Shocks and LVEF Improvement
Description
Evaluate the most clinically useful efficacy endpoint of ENCORE treatment, namely, number of patients with reduction specifically in ICD shocks (6 months before vs. 6 months after treatment, with a 6 week blanking period immediately after treatment). For patients with PVC-induced cardiomyopathy, the most clinically useful efficacy will be improvement in cardiac function in the setting of any improvement in PVC burden.
Time Frame
6 months
Title
Number of Participants With Reduction in Ventricular Tachycardia (VT) Therapies Between 6 and 12 Months
Description
Evaluate longer-term durability endpoint of ENCORE treatment, as defined by number of patients with reduction in VT therapies (ATP or ICD shock or sustained (>30 sec) slow VT and ICD shock alone) during the early phase (treatment to 6 months, with 6 week blanking period) vs. the late phase (6 months to 1 year). For patients with PVC-induced cardiomyopathy, the longer-term durability efficacy will be persistence of any reduction in PVC burden based on ambulatory heart monitors during early phase vs. late phase.
Time Frame
12 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
DOCUMENTED VT:
Patient must have documented sustained monomorphic ventricular tachycardia as documented on either a 12-lead ECG or intracardiac ICD interrogation
- OR-
Monomorphic PVCs documented on a 12-lead ECG.
ANTIARRHYTHMIC MEDICATION: Patient must have failed or become intolerant to at least one antiarrhythmic medication (amiodarone, sotalol, or mexiletine).
-AND-
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).
MINIMUM VT BURDEN: Patient must have either:
At least 3 VT episodes (sustained VT, ICD ATP or ICD shock) over previous 6 months prior to enrollment -OR-
>20% PVC burden with a cardiomyopathy (LVEF<50%)
Patient must be deemed medically fit for stereotactic body radiation therapy by the treating physician.
Patient must be > 18 years old.
Patient must be able to understand and be willing to sign an IRB approved written informed consent document.
-
Exclusion Criteria:
Patient must not have past history of radiotherapy within the projected treatment field.
Advanced symptomatic heart failure as defined as NYHA Class IV heart failure (inotrope dependent and/or current left-ventricular assist device (LVAD))
Polymorphic VT or ventricular fibrillation (VF) as a clinical heart rhythm (as determined by 12-lead ECG and/or ICD interrogation).
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.
Advanced myocardial scar substrate that would require stereotactic delivery to a target volume deemed unsafe by the treating physician.
Unlikely to live 12 months, in the absence of VT, as best based on clinical judgment by the treating and enrolling physicians.
Patient must not be pregnant and/or breastfeeding and must have a negative pregnancy test within 14 days of study entry.
-
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Phillip Cuculich, MD
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
Yes
IPD Sharing Plan Description
Open sharing at the time of publication of results
Citations:
PubMed Identifier
30586734
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.
Results Reference
derived
Learn more about this trial
Phase I/II Study of EP-guided Noninvasive Cardiac Radioablation for Treatment of Ventricular Tachycardia
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