Clinical trial NCT05524077: Catheter Ablation Versus Anti-arrhythmic Drugs for Ventricular Tachycardia
Official title: Catheter Ablation Versus Anti-arrhythmic Drugs for Ventricular Tachycardia (CAAD-VT): A Randomised Trial
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Disease Structural Disorder
Ventricular Tachycardia
Cardiomyopathy, Dilated
Sarcoidosis
Cardiomyopathy, Hypertrophic
Cardiomyopathy Ischemic
Cardiomyopathy, Familial
Arrhythmogenic Right Ventricular Cardiomyopathy 1
Arrhythmogenic Left Ventricular Cardiomyopathy
Lead sponsor: Western Sydney Local Health District
Sponsor class: OTHER
First posted: 2022-09-01
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Composite of Recurrent VT or VT storm
timeFrame: 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.
measure: Death
timeFrame: 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.
Secondary outcomes:
measure: Recurrent sustained VT
timeFrame: 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.
measure: VT storm
timeFrame: 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.
measure: VT burden
timeFrame: 6 months after randomisation, with a 30-day treatment 'blanking' period after treatment initiation; and 6 months before randomisation
measure: Cardiovascular hospitalisation
timeFrame: 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.
measure: Mortality
timeFrame: Outcome will be assessed at 3-, 6-, 12-, 18-, 24-, 30-, 36- months post-randomisation. Events will be included at any time after randomisation.
measure: Effect of intervention on ventricular function
timeFrame: 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.
Other outcomes:
Locations:
city: Garran
country: Australia
facility: The Canberra Hospital
state: Australian Capital Territory
city: Blacktown
country: Australia
facility: Blacktown Hospital
state: New South Wales
city: Camperdown
country: Australia
facility: Royal Prince Alfred Hospital
state: New South Wales
city: Kingswood
country: Australia
facility: Nepean Hospital
state: New South Wales
city: New Lambton Heights
country: Australia
facility: John Hunter Hospital
state: New South Wales
city: Saint Leonards
country: Australia
facility: Royal North Shore Hospital
state: New South Wales
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
city: Chermside
country: Australia
facility: The Prince Charles Hospital
state: Queensland
city: Southport
country: Australia
facility: Gold Coast University Hospital
state: Queensland
city: Adelaide
country: Australia
facility: Royal Adelaide Hospital
state: South Australia
city: Melbourne
country: Australia
facility: The Alfred Hospital
state: Victoria
city: Parkville
country: Australia
facility: The Royal Melbourne Hospital
state: Victoria
Study officials:
affiliation: Western Sydney Local Health District
name: Saurabh Kumar, MBBS, PhD
role: PRINCIPAL_INVESTIGATOR
References: