Catheter Ablation Versus Anti-arrhythmic Drugs for Ventricular Tachycardia

Not Applicable

Recruiting

• Conditions: Heart Disease Structural Disorder; Ventricular Tachycardia; Cardiomyopathy, Dilated; Sarcoidosis; Cardiomyopathy, Familial; Arrhythmogenic Right Ventricular Cardiomyopathy 1; Arrhythmogenic Left Ventricular Cardiomyopathy; Cardiomyopathy Ischemic; Cardiomyopathy, Hypertrophic
• Interventions: Procedure: Ablation; Drug: Anti-arrhythmic Drugs (AADs)

• Registration Number: NCT05524077
• Lead Sponsor: Western Sydney Local Health District

Brief Summary

Sudden cardiac death (SCD) due to recurrent ventricular tachycardia (VT) is an important clinical sequela in patients with structural heart disease. VT generally occurs as a result of electrical re-entry in the presence of arrhythmogenic substrate (scar). Scar tissue forms due to an ischemic cardiomyopathy (ICM) from prior coronary obstructive disease or a non-ischemic cardiomyopathy (NICM) from an inflammatory or genetic disease.

AADs can reduce VT recurrence, but have significant limitations in treatment of VT. For example, amiodarone has high rates of side effects/toxicities and a finite effective usage before recurrence. ICDs prevent cardiac arrest and sudden death from VT, but do not stop VT occurring. Recurrent VT and ICD therapies decrease QOL, increase hospital visits, mortality, morbidity and risk of death. Improvement in techniques for mapping and ablation of VT have made CA an alternative.

Currently, there is limited evidence to guide clinicians either toward AAD therapy or CA in patients with NICM. This data shows significant benefit of CA over medical therapy in terms of VT free survival, survival free of VT storm and VT burden. Observational studies suggest that CA is effective in eliminating VT in NICM patients who have failed AADs, resulting in reduction of VT burden and AAD use over long term follow up. Furthermore, there is limited data on the efficacy of CA in early ICM with VT, or advanced ICM with VT. RCT data is almost exclusively on patients with modest ICM with VT, and this is not representative of the real-world scenario of patients with structural heart disease presenting with VT.

Therefore the primary objective is to determine in all patients with structural heart disease and spontaneous or inducible VT, if catheter ablation compared to standard medical therapy with anti-arrhythmic drugs results in a reduction of a composite endpoint of recurrent VT, VT storm and death at a median follow up of 18 months.

Detailed Description

Not available

Study Timeline

• Study Start: 2020-07-08
• Status Verified: 2022-08
• Study First Submitted: 2022-08-24
• Study First Submitted QC: 2022-08-29
• Last Update Submitted: 2022-08-29
• Study First Posted: 2022-09-01
• Last Update Posted: 2022-09-01
• Primary Completion: 2026-06-30
• Study Completion: 2026-06-30

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 162

Inclusion Criteria

Patients will be eligible for inclusion if they have:

1. ≥1 prior episode of sustained VT in the prior 6 months;

   1. Spontaneous VT: ≥1 episode of monomorphic VT treated by anti-tachycardia pacing (ATP) and/or internal shock by an ICD; lasting ≥30 seconds in the absence of intra-cardiac device therapy that could either be self-terminating or require reversion by pharmacological therapy or external cardioversion;
   2. Spontaneous VT: ≥1 episode of sustained spontaneous monomorphic VT lasting ≥30 seconds documented on Holter, ECG, Loop recorder or other cardiac monitoring device that could either be self-terminating or require reversion by pharmacological therapy or external cardioversion;
   3. Inducible VT: with syncope or palpitations - inducible VT defined as sustained monomorphic VT of CL ≥200 ms lasting for ≥10 s during a cardiac electrophysiology study (note with 4 extrastimuli with or without provocation with isoprenaline);

2. Already a recipient of an implanted cardiac device such as a pacemaker, defibrillator or a cardiac resynchronisation therapy device and/or is indicated to receive one given a new diagnosis of structural heart disease, based on current guideline recommendations;

3. Aged ≥18 years.

Exclusion Criteria

Patients will be excluded if they are:

1. Unable or unwilling to provide informed consent or patients physician feels there is not significant equipoise to justify randomisation;
2. Women who are pregnant, breast feeding;
3. Medical illness with an anticipated life expectancy <3 months;
4. Unable to complete study procedures or unwilling to be followed up;
5. Have a concomitant illness, physical impairment or mental condition which in the opinion of the study team/ primary care physician could interfere with the conduct of the study including outcome assessments;
6. Known channelopathy such as long QT, short QT, Brugada syndrome, catecholaminergic polymorphic VT;
7. Known prior diagnosis of no structural heart disease, or idiopathic ventricular arrhythmia.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Ablation	Ablation	Patients will be expected to have a catheter ablation procedure within 2 weeks post randomisation and no longer than 30 days post randomisation. Medical therapy can be used as a temporising measure before catheter ablation, as is standard of care. If there is breakthrough VT during the period before the clinical procedure, standard practice will be followed in stabilising the ventricular tachycardia (VT) including intravenous short acting anti-arrhythmic drugs (AAD), admission to hospital, internal or external cardioversion. However, preference will be given to scheduling the procedure within 24-48 hours in this situation.
Anti-arrhythmic drugs (AAD)	Anti-arrhythmic Drugs (AADs)	Patients managed with medical therapy alone by their usual medical practitioners. A protocol aligned with standard clinical care/current clinical guidelines will be provided for guidance, the objective being that the control arm replicates what would constitute standard of care for patients with ventricular tachycardia managed with a non-interventional approach.

Primary Outcome Measures

Name	Time	Method
Composite of Recurrent VT or VT storm	Primary outcome will be assessed at 3-, 6-, 12-, 18-, 24-, 30-, 36- months post-randomisation. VT/VT Storm events after the 30-day treatment 'blanking' period after treatment initiation will be included.	VT (detected by cardiac device as lasting ≥30 seconds or shorter in duration if treated by the ICD).; VT storm (three or more documented episodes of VT within 24 hours or incessant VT).
Death	Primary outcome will be assessed at 3-, 6-, 12-, 18-, 24-, 30-, 36- months post-randomisation. Death events at any time after randomisation will be included.	Death (at any time) due to any cause.

Secondary Outcome Measures

Name	Time	Method
Recurrent sustained VT	Outcome will be assessed at 3-, 6-, 12-, 18-, 24-, 30-, 36- months post-randomisation. VT events will be included after the 30-day treatment 'blanking' period after treatment initiation.	Recurrent sustained VT detected 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)
VT storm	Outcome will be assessed at 3-, 6-, 12-, 18-, 24-, 30-, 36- months post-randomisation. VT storm events will be included after the 30-day treatment 'blanking' period after treatment initiation.	Three or more documented episodes of VT within 24 hours or incessant VT
Cardiovascular hospitalisation	Outcome will be assessed at 3-, 6-, 12-, 18-, 24-, 30-, 36- months post-randomisation. Events will be included after the 30-day treatment 'blanking' period after treatment initiation.	All cardiovascular hospitalisation; heart failure; hospitalisation for arrhythmia
Effect of intervention on ventricular function	Outcome will be assessed at 3-, 6-, 12-, 18-, 24-, 30-, 36- months post-randomisation. Events will be included after the 30-day treatment 'blanking' period after treatment initiation.	Effect of intervention on ventricular function as assessed by transthoracic echocardiography from baseline to 6-, 12-, 24- and 36-months' post intervention
VT burden	6 months after randomisation, with a 30-day treatment 'blanking' period after treatment initiation; and 6 months before randomisation	VT burden (number of episodes of VT in the preceding 6 months compared to the 6 months after randomisation and therapy)
Mortality	Outcome will be assessed at 3-, 6-, 12-, 18-, 24-, 30-, 36- months post-randomisation. Events will be included at any time after randomisation.	All-cause mortality; cardiovascular mortality; non-cardiac death

Trial Locations

Locations (12)

Blacktown Hospital; 🇦🇺 Blacktown, New South Wales, Australia

Nepean Hospital; 🇦🇺 Kingswood, New South Wales, Australia

John Hunter Hospital; 🇦🇺 New Lambton Heights, New South Wales, Australia

Royal North Shore Hospital; 🇦🇺 Saint Leonards, New South Wales, Australia

Westmead Hospital; 🇦🇺 Westmead, New South Wales, Australia

Royal Prince Alfred Hospital; 🇦🇺 Camperdown, New South Wales, Australia

Royal Adelaide Hospital; 🇦🇺 Adelaide, South Australia, Australia

The Canberra Hospital; 🇦🇺 Garran, Australian Capital Territory, Australia

The Prince Charles Hospital; 🇦🇺 Chermside, Queensland, Australia

Gold Coast University Hospital; 🇦🇺 Southport, Queensland, Australia

The Royal Melbourne Hospital; 🇦🇺 Parkville, Victoria, Australia

The Alfred Hospital; 🇦🇺 Melbourne, Victoria, Australia