Stereotactic Ablative Radiotherapy for the Treatment of Refractory Ventricular Tachycardia (SABRE-VT)

Ventricular tachycardia (VT) is an abnormal rhythm arising from the bottom chambers (ventricles) of the heart. The hearts of most patients who develop VT have been previously damaged by a myocardial infarction (heart attack) or other heart muscle diseases (cardiomyopathies). The damage produces scar or fatty deposits that conduct electrical impulses slowly allowing VT to occur. Recurrent episodes of VT can compromise heart function and increase mortality.

VT is prevented by special drugs but these are not always effective and can have many side effects. Most patients with VT will also have a specialised device called an implantable defibrillator (ICD) implanted. The ICD treats VT by either stimulating the heart rapidly or delivering a shock to it. ICDs are very effective but the shocks are painful and have a big impact on quality of life. If VT occurs despite optimal drug treatment, patients undergo an invasive procedure called catheter ablation. Here, wires are passed into the heart from the blood vessels in the leg and the damaged heart muscle causing the VT is identified whilst the heart is in VT. An electrical current is passed down the wire making its tip heat up allowing discrete burns (ablation) to be placed inside the heart. The ablated heart muscle doesn't conduct electricity which stops the VT and prevents it recurring.

Some patients are so frail that ablation cannot be performed safely. A recent clinical trial has shown that VT can be treated in such patients using radiotherapy, which is usually used to treat tumours with high energy radiation. This approach is non-invasive, painless and requires no sedation or anaesthesia.

This study will test whether VT can be successfully treated using stereotactic ablative radiotherapy. This can deliver high dose radiotherapy very precisely, whilst minimising the risk of damage to healthy tissues.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure; Ventricular Tachycardia; Radiotherapy; Complications; Structural Heart Abnormality
• Intervention / Treatment: Radiation: Stereotactic ablative radiotherapy

Detailed Description

Principal objectives:

1. To determine the safety and efficacy of stereotactic ablative radiotherapy (SABR) for the treatment of VT refractory to conventional therapies.

Background:

VT is an abnormal heart rhythm arising from either of the bottom chambers of the heart (ventricles). Most patients with VT have scarring or fatty deposits in the heart muscle caused by a previous heart attack or a heart muscle problem called a cardiomyopathy. The abnormal heart muscle conducts electricity slowly allowing VT to occur. Most patients with VT have a device called an implantable defibrillator (ICD) fitted to treat VT. The ICD has wires going into the heart from a small generator that is inserted under the skin below the left collar bone. ICDs stop VT by stimulating the heart rapidly or by shocking the heart which is very painful and can stun the heart temporarily, weakening its pumping function. Patients who experience a lot of VT can have more admissions to hospital, worsening heart failure and a poorer quality of life, as well as a higher risk of dying. Consequently, all patients are treated with drugs to prevent VT but these are not always effective. If VT keeps recurring, many patients undergo an invasive procedure called catheter ablation where wires are passed into the heart from the leg and the part of the ventricles causing the VT identified. A high frequency electrical current is then passed down one of the wires making its tip heat up allowing discrete burns (ablation) to be placed on the culprit area, which stops the VT and prevents it from recurring. Performing catheter ablation in such patients is a high risk procedure and the overall complication rate is between 5 - 15% in experienced centres. Some patients have recurrent VT despite catheter ablation or the VT cannot be ablated because the patient is too frail, or the VT causes a significant fall in the blood pressure resulting in cardiac arrest (heart stops beating).

In the last 6 years, several case reports and series have been published showing that radiotherapy using different types of linear accelerator machines (including the Cyberknife) can successfully and safely ablate VT. Most recently, a prospective, randomised trial (ENCORE-VT) has reported a dramatic reduction in VT following radioablation.

This study will therefore assess our ability to perform stereotactic radioablation for VT at St Bartholomew's Hospital. We will determine procedural success and safety. Patients will be assessed 3, 6 and 12 months after the treatment and their burden of VT determined by checking the ICD.

• Study Type: Interventional
• Enrollment (Anticipated): 6
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Hakam Abbas, MSc; Phone Number: 020 37658635; Email: Hakam.abbass@nhs.net

Study Locations

• United Kingdom
  • London, United Kingdom, EC1A 7BE
    • Recruiting
    • St Bartholomew's Hospital
    • Contact: MEHUL DHINOJA, FRCP; Phone Number: 02073777000; Email: mehul.dhinoja@nhs.net
    • Principal Investigator: MEHUL DHINOJA, FRCP
    • Sub-Investigator: Anish Bhuva, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. They are at least 18-85 years old.
2. They have recurrent VT (at least three episodes in the preceding six months) requiring therapy from an ICD, that is refractory to conventional treatments - both maximally tolerated doses of anti- arrhythmic drugs and/or conventional catheter ablation.
3. They are too frail or do not wish to undergo conventional catheter ablation.
4. They have not had previous radiotherapy to the anticipated treatment field.

Exclusion Criteria:

1. They have polymorphic VT or ventricular fibrillation (VF).
2. They have inotrope-dependent heart failure or a left ventricular assist device (LVAD) in situ.
3. They are unlikely to live more than 12 months irrespective of the VT.
4. There is a potentially reversible cause for the VT e.g. critical coronary artery disease or a metabolic problem such as an overactive thyroid gland.
5. They are unable to provide informed consent.
6. They have had previous radiotherapy to the anticipated treatment field.
7. The patient weighs in excess of 170kg (maximum weight capacity of the tables in the imaging department).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment arm; Treatment with stereotactic ablative radiotherapy	Radiation: Stereotactic ablative radiotherapy; Stereotactic ablative radiotherapy will be delivered to a volume of ventricular myocardium responsible for the clinical ventricular tachycardia.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in quality of life and cardiac complications as assessed by clinical history, SF-36 questionnaire, electrocardiogram and echocardiography.	The number of serious adverse events at three months after treatment. This will be determined as follows: Clinical history from and examination of the patients assessing for new chest pains, breathlessness or coughing.; SF-36 quality of life questionnaire.; Echocardiography to assess for pericardial effusion that could indicate radiation-induced pericarditis.; Electrocardiogram to assess for pericarditis or myocarditis caused by radiation.	3 months
Efficacy endpoint - Cumulative VT burden 6 months before and 6 months after radiotherapy.	There will be a six week blanking period after radiotherapy to allow for ablation effect. The burden of VT will be assessed by interrogating the patient's ICD and assessing the number of episodes of non-sustained and sustained VT as well as the number of ICD therapies delivered.	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
VT burden	Cumulative VT burden in the second 6 months following radiotherapy. This will be assessed by ICD interrogation as described above.	6 months
Survival	Overall survival at 3, 6 and 12 months following radiotherapy.	12 months
Cardiac function changes from radiotherapy	Absolute change in numerical left ventricular ejection fraction assessed with echocardiography, at 3, 6 and 12 months.	12 months
Radiotherapy impact on ICD function	Deterioration in implantable cardioverter-defibrillator function attributable to radiotherapy at 3, 6 and 12 months. This will be determined by interrogating the ICD and measuring the change in ICD defibrillator lead impedance.	12 months
Quality of life assessment using SF-36 questionnaire	The SF-36 questionnaire will be used at 3, 6 and 12 months to assess this.	12 months
Heart failure status using New York Heart Association (NYHA) breathlessness class.	Patients will be assessed at 3, 6 and 12 months by taking a history for breathlessness, scaled I to IV according to their NYHA class.	12 months
Cardiac conduction system status measured by ECG QRS duration.	An electrocardiogram will be performed at 3, 6 and 12 months to look for any changes in the QRS complex duration.	12 months

Collaborators and Investigators

• Sponsor: Barts & The London NHS Trust

Study record dates

Study Major Dates

• Study Start (Anticipated): January 21, 2023
• Primary Completion (Anticipated): May 2, 2024
• Study Completion (Anticipated): May 2, 2026

Study Registration Dates

• First Submitted: February 21, 2022
• First Submitted That Met QC Criteria: January 13, 2023
• First Posted (Estimate): January 24, 2023

Study Record Updates

• Last Update Posted (Estimate): January 24, 2023
• Last Update Submitted That Met QC Criteria: January 13, 2023
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Keywords: radiotherapy; heart failure; ventricular tachycardia
• Additional Relevant MeSH Terms: Pathologic Processes; Heart Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Cardiac Conduction System Disease; Heart Failure; Tachycardia; Tachycardia, Ventricular
• Other Study ID Numbers: 262246

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