Ventricular TachycardiaPhase 1/2ENCORE-VTNCT02919618
Phase I/II Study of EP-guided Noninvasive Cardiac Radioablation for Treatment of Ventricular Tachycardia
A Phase 1/2 study testing stereotactic body radiotherapy (SBRT) in people with Ventricular Tachycardia and Cardiomyopathy, run by Washington University School of Medicine at 1 site in United States.
Trial summary
Phase I/II Study of EP-guided Noninvasive Cardiac Radioablation (ENCORE) for Treatment of Ventricular Tachycardia Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Ventricular Tachycardia, Cardiomyopathy, Premature Ventricular Contractions
- What is being tested?
- stereotactic body radiotherapy (SBRT)
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2016to 1 Jan 2024
- Phase
- Phase 1/2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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-
Show all 14Show fewer
- 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.
- -
Who cannot join
- 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.
- -
Trial locations and contacts
1 site in 1 country.
United States1 site
Washington University School of Medicine
St Louis, Missouri, 63110
About this study
Phase I/II Study of EP-guided Noninvasive Cardiac Radioablation (ENCORE) for Treatment of Ventricular Tachycardia
Read the 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.
- Being tested
- stereotactic body radiotherapy (SBRT)
- Keywords
- Ventricular Tachycardia, Ablation, Noninvasive
- Medical subject headings
- Tachycardia, Ventricular, Cardiomyopathies, Ventricular Premature Complexes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
stereotactic body radiotherapy (SBRT)Radiation
(Cardiac ablative radiotherapy)
| Study group | Role | What they receive |
|---|---|---|
| stereotactic body radiotherapy (SBRT) | Experimental | 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. Receives: Radiation: stereotactic body radiotherapy (SBRT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: < or = 90 days
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.
Measured: 12 months (6mo prior to and 6mo post SBRT)
Secondary outcomes (7)
Overall Survival
Determine six-month and twelve-month survival (overall mortality endpoint) after treatment with ENCORE.
Measured: 12 months
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.
Measured: 90 days to 12 months
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.
Measured: 6 week, 6 month, 12 month
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.
Measured: 6 months
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.
Measured: 6 months
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.
Measured: 6 months
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.
Measured: 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Sep 2016 (estimated)
- Study startJul 2016
- Primary completion23 Jul 2018
- Study completion1 Jan 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ventricular TachycardiaStudies of the same condition, open and under way.
- More trials run by Washington University School of MedicineThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Noninvasive Cardiac Radioablation, all subjects
- Masking
- None (open label)
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Washington University School of Medicine
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Phillip Cuculich, Washington University School of Medicine
- Investigators
- Phillip Cuculich, MD, Principal investigator, Washington University School of Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02919618
- Sponsor's protocol ID
- 201606081
- Acronym
- ENCORE-VT
- Status last verified
- Jul 2024
- First submitted
- 28 Sep 2016
- Last updated
- 21 Aug 2024
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: Open sharing at the time of publication of results
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.
PubMed 30586734
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I/II Study of EP-guided Noninvasive Cardiac Radioablation for Treatment of Ventricular Tachycardia
- ClinicalTrials.gov ID
- NCT02919618
- Acronym / sponsor ID
- ENCORE-VT / 201606081
- Keywords
- Ventricular Tachycardia, Ablation, Noninvasive
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Washington University School of MedicineUniversity, hospital or other
- Study start
- Jul 2016 (actual)
- Primary completion
- 23 Jul 2018 (actual)
- Study completion
- 1 Jan 2024 (actual)
- First posted
- 29 Sep 2016 (estimated)
- Results
- Posted 10 Sep 2019
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Noninvasive Cardiac Radioablation, all subjects
| Arm | Type | Receives |
|---|---|---|
| stereotactic body radiotherapy (SBRT) | Experimental | Radiation: 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- DOCUMENTED VT:
- 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:
Key exclusion criteria (8 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| stereotactic body radiotherapy (SBRT)(Cardiac ablative radiotherapy) | Radiation | stereotactic body radiotherapy (SBRT) |
Primary outcome
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.
7 secondary outcomes
Overall Survival
Time frame: 12 months
Number of Adverse Events That Are Possibly/Probably/Definitely Related to Study Treatment
Time frame: 90 days to 12 months
Health Related Quality of Life (HRQOL)
Time frame: 6 week, 6 month, 12 month
Number of Participants With a 50% Reduction in Ventricular Tachycardia (VT) Burden
Time frame: 6 months
Number of Participants With a 95% Reduction in Ventricular Tachycardia (VT) Burden
Time frame: 6 months
Number of Participants With Reduction in ICD Shocks and LVEF Improvement
Time frame: 6 months
Number of Participants With Reduction in Ventricular Tachycardia (VT) Therapies Between 6 and 12 Months
Time frame: 12 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2024.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 30586734Robinson 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.
- Individual participant dataSharing planned: Yes. Open sharing at the time of publication of results
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Phillip Cuculich, MD principal investigator
Washington University School of Medicine
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing stereotactic body radiotherapy (SBRT) in people with Ventricular Tachycardia and Cardiomyopathy, run by Washington University School of Medicine at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Sep 2019). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Number of Serious Adverse Events (time frame: < or = 90 days). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02919618, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2024; AzTrials last refreshed its copy on 8 Nov 2026.