We're building a better ClinicalTrials.gov. Check it out and tell us what you think!
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02919618
Recruitment Status : Active, not recruiting
First Posted : September 29, 2016
Results First Posted : September 10, 2019
Last Update Posted : December 2, 2021
Sponsor:
Information provided by (Responsible Party):
Phillip Cuculich, Washington University School of Medicine

Tracking Information
First Submitted Date  ICMJE September 28, 2016
First Posted Date  ICMJE September 29, 2016
Results First Submitted Date  ICMJE July 1, 2019
Results First Posted Date  ICMJE September 10, 2019
Last Update Posted Date December 2, 2021
Actual Study Start Date  ICMJE July 2016
Actual Primary Completion Date July 23, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 20, 2019)
  • Number of Serious Adverse Events [ Time Frame: < or = 90 days ]
    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 [ Time Frame: 12 months (6mo prior to and 6mo post SBRT) ]
    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.
Original Primary Outcome Measures  ICMJE
 (submitted: September 28, 2016)
  • Acute (≤ 90 days) safety of noninvasive stereotactic cardiac ablation radiotherapy (ENCORE). [ Time Frame: < or = 90 days ]
    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.
  • Efficacy of ENCORE [ Time Frame: 12 months ]
    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.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: August 20, 2019)
  • Overall Survival [ Time Frame: 12 months ]
    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 [ Time Frame: 90 days to 12 months ]
    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) [ Time Frame: 6 week, 6 month, 12 month ]
    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 [ Time Frame: 6 months ]
    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 [ Time Frame: 6 months ]
    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 [ Time Frame: 6 months ]
    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 [ Time Frame: 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: September 28, 2016)
  • Overall mortality [ Time Frame: 12 months ]
    Determine six-month and twelve-month survival (overall mortality endpoint) after treatment with ENCORE.
  • Late toxicity [ Time Frame: 90 days to 12 months ]
    Toxicities that occur after treatment, but are not acutely ascribed to treatment
  • Health related quality of life (HRQOL) [ Time Frame: 6 week, 6 month, 12 month ]
    Assessing for positive or negative changes in quality of life related to treatment and its results based on scores from standardized SF-36 questionnaire
  • Stricter efficacy (50% reduction) [ Time Frame: 6 months ]
    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.
  • Strictest efficacy (95% reduction) [ Time Frame: 6 months ]
    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.
  • Most clinically useful efficacy (ICD shocks & LVEF improvement) [ Time Frame: 6 months ]
    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.
  • Longer-term durability (6 to 12 month period) [ Time Frame: 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.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Phase I/II Study of EP-guided Noninvasive Cardiac Radioablation for Treatment of Ventricular Tachycardia
Official Title  ICMJE Phase I/II Study of EP-guided Noninvasive Cardiac Radioablation for Treatment of Ventricular Tachycardia
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Ventricular Tachycardia
  • Cardiomyopathy
  • Premature Ventricular Contractions
Intervention  ICMJE Radiation: stereotactic body radiotherapy (SBRT)
(Cardiac ablative radiotherapy)
Study Arms  ICMJE Experimental: stereotactic body radiotherapy (SBRT)
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: Radiation: stereotactic body radiotherapy (SBRT)
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: August 20, 2019)
19
Original Estimated Enrollment  ICMJE
 (submitted: September 28, 2016)
20
Estimated Study Completion Date  ICMJE January 2024
Actual Primary Completion Date July 23, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

    -

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02919618
Other Study ID Numbers  ICMJE 201606081
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: Open sharing at the time of publication of results
Supporting Materials: Study Protocol
Current Responsible Party Phillip Cuculich, Washington University School of Medicine
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Washington University School of Medicine
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Phillip Cuculich, MD Washington University School of Medicine
PRS Account Washington University School of Medicine
Verification Date December 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP