Radiotherapy vs Catheter Ablation for Ventricular Tachycardia in Structural Heart Disease (Radioablate)

The goal of this randomized clinical trial is to test the efficacy of stereotactic body radiation therapy (SBRT) in treating ventricular tachycardia (VT) in patients with advanced structural heart disease. The main questions it aims to answer are:

• What is the efficacy of SBRT compared to catheter ablation (CA) in achieving a ≥ 75% reduction in VT burden at 6 months
• What is the comparable safety profile of SBRT vs CA Researchers will compare SBRT and CA (standard of care).

Study Overview

• Status: Not yet recruiting
• Conditions: Arrhythmias, Cardiac; Cardiomyopathies; Ventricular Tachycardia; Ventricular Arrythmia
• Intervention / Treatment: Radiation: SBRT; Procedure: CA

Detailed Description

Hypothesis

We hypothesise that in an open label randomised controlled trial of patients with advanced structural heart disease and ventricular tachycardia (VT) that stereotactic body radiation therapy (SBRT) will be superior in reducing VT burden compared to standard care comprising of catheter ablation (CA) and routine medical care with acceptable safety and adverse events.

Aims

This is a trial to examine if in an open label randomised trial of 60 patients with structural heart disease and VT followed for 3 years with a minimum follow up of 1 year of SBRT compared CA results in:

1. An improvement in a primary outcome of proportion of patients with a ≥75% reduction in VT burden in the 6 months following intervention compared to the 6 months intervention
2. Comparable safety profile (serious adverse events [SAE] and adverse events of special interest [AESI] at 6 months;
3. reduction in secondary endpoints at 6, 12, 24 and 36 months of: any VT recurrence, absolute % reduction in VT burden compared to 6 months pre-treatment, number of anti-arrhythmic drugs (AADs) compared to pre-treatment, cardiovascular hospitalisation, all-cause mortality, cardiac transplantation, combined endpoint of cardiovascular hospitalisation/transplant/mortality, SAE and AESI from treatment, ventricular function abd change of quality of life (QOL) metrics (at 12 months).

• Study Type: Interventional
• Enrollment (Estimated): 60
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Saurabh Kumar, MBBS | PhD; Phone Number: +61 (02)88908140; Email: saurabh.kumar@health.nsw.gov.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Structural heart disease (including ischaemic cardiomyopathy , non-ischaemic cardiomyopathy or congenital heart disease and defined as any one of

   1. segmental or global decreased ventricular wall motion as defined by TTE, CT or cMRI
   2. myocardial hypertrophy
   3. myocardial scar (evidenced by late gadolinium enhancement on cMRI, wall thinning on cardiac CT, low voltage on electrophysiological study or abnormal intracardiac echocardiography)

2. Recurrent monomorphic VT which can include

   1. at least one episode of VT treated by ICD and/or
   2. sustained VT (lasting >30s) and/or
   3. inducible sustained VT on invasive electrophysiological study (EPS) or non-invasive programmed stimulation (NIPS)
3. PAINESD score of ≥9 points and/or at least moderate risk of VT recurrence or death as defined by the I-VT score. Both are validated tools used clinically to identify patient at high risk of VT recurrence and/or mortality after CA.

Exclusion Criteria:

1. Age < 18 years
2. Life expectancy < 3 months
3. Catheter ablation deemed futile or with prohibitive risk by cardiac electrophysiologist.
4. Unwilling or unable to provide consent
5. Known cardiac channelopathies (e.g. Catecholaminergic polymorphic ventricular tachycardia (CPVT), long- or short QT syndrome, Brugada syndrome)
6. Contraindications to radiotherapy as deemed by referring physician and/or radiation oncologist
7. Pregnancy or breast feeding

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Stereotactic body radiation therapy; SBRT within 6 weeks of randomisation guided by previous electrophysiology studies, electrocardiograms and cardiac imaging.	Radiation: SBRT; Delivery of 25Gy in a single dose fraction to target area within 6 weeks of randomization
Active Comparator: Catheter ablation; CA within 6 weeks of randomisation (constituting standard of care for patients with VT and structural heart disease)	Procedure: CA; CA (endocardial and/or epicardial at operator discretion) within 6 weeks of randomization.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VT burden	Change in proportion of patients with a ≥75% reduction in VT burden at 6 months (number of VT episodes in 6 months post treatment compared to the number of VT episodes in the 6 months prior to randomisation excluding a 6-week blanking period after treatment initiation)	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrent sustained VT	Recurrent sustained VT ascertained by implanted cardioverter defibrillator (ICD) (VT identified and treated by the ICD with anti-tachycardia pacing (ATP) and/or internal ICD delivered shock or ≥30 seconds of VT if untreated by ICD	6, 12, 24 and 36 months
VT storm	VT storm (three or more documented episodes of VT within 24 hours or incessant VT)	6, 12, 24 and 36 months
Absolute VT burden	Absolute percentage reduction in VT burden compared to pre-ablation	6, 12, 24 and 36 months
Serious Adverse Events (SAE) and Adverse Events of Special Interest (AESI)	SAE and AESI related to effects of SBRT; SAE and AESI related to standard care e.g. medical anti-arrhythmic drug therapy or catheter ablation or heart transplantation	At all time points up to 36 months
ICD shocks	Implantable Cardioverter Defibrillator shocks	6, 12, 24 and 36 months
Hospitalization	Cardiovascular as well as specifically heart failure and arrhythmia	6, 12, 24 and 36 months
All cause mortality	All cause mortality	6,12, 24 and 36 months
Cardiovascular Mortality	Cardiovascular mortality	6,12, 24 and 36 months
Composite outcome of VT recurrence/hospitalisation/death/ cardiac transplantation	Composite outcome as above	6,12, 24 and 36 months
Ventricular function	As determined by echocardiography (ejection fraction, speckle tracking echocardiography)	6,12, 24 and 36 months
Quality of Life as per Short Form - 36 (SF-36) Score	Change in quality of life at 6 and 12 months (compared to pre-intervention) as measured by Short Form- 36 (SF-36) [0-100 scale, 0 is equivalent to maximum disability and a score of 100 is equivalent to no disability].	6,12, 24 and 36 months
Quality of Life as per Implantable Cardioverter Defibrillator Concerns Questionnaire (ICDC) score	Change in quality of life at 6 and 12 months (compared to pre-intervention) as measured by Implantable Cardioverter Defibrillator Concerns Questionnaire (ICDC) score. [0-100 scale, 100 equivalent to maximum concern]	6,12, 24 and 36 months
Number of AADs	Number of AADs at time points following randomization	6,12, 24 and 36 months

Collaborators and Investigators

• Sponsor: Western Sydney Local Health District
• Collaborators: National Heart Foundation, Australia; University of Sydney

Study record dates

Study Major Dates

• Study Start (Estimated): May 20, 2024
• Primary Completion (Estimated): May 20, 2026
• Study Completion (Estimated): May 20, 2027

Study Registration Dates

• First Submitted: January 2, 2024
• First Submitted That Met QC Criteria: April 7, 2024
• First Posted (Actual): April 11, 2024

Study Record Updates

• Last Update Posted (Actual): May 1, 2024
• Last Update Submitted That Met QC Criteria: April 29, 2024
• Last Verified: April 1, 2024

More Information

Terms related to this study

• Keywords: catheter ablation; radioablation; non invasive; stereotactic body radiation therapy
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Cardiac Conduction System Disease; Heart Diseases; Arrhythmias, Cardiac; Tachycardia; Tachycardia, Ventricular; Cardiomyopathies
• Other Study ID Numbers: ETH02659

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No