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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05524077




Registration number
NCT05524077
Ethics application status
Date submitted
24/08/2022
Date registered
1/09/2022
Date last updated
1/09/2022

Titles & IDs
Public title
Catheter Ablation Versus Anti-arrhythmic Drugs for Ventricular Tachycardia
Scientific title
Catheter Ablation Versus Anti-arrhythmic Drugs for Ventricular Tachycardia (CAAD-VT): A Randomised Trial
Secondary ID [1] 0 0
CAAD-VT
Universal Trial Number (UTN)
Trial acronym
CAAD-VT
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart Disease Structural Disorder 0 0
Ventricular Tachycardia 0 0
Cardiomyopathy, Dilated 0 0
Sarcoidosis 0 0
Cardiomyopathy, Hypertrophic 0 0
Cardiomyopathy Ischemic 0 0
Cardiomyopathy, Familial 0 0
Arrhythmogenic Right Ventricular Cardiomyopathy 1 0 0
Arrhythmogenic Left Ventricular Cardiomyopathy 0 0
Condition category
Condition code
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Cardiovascular 0 0 0 0
Other cardiovascular diseases
Inflammatory and Immune System 0 0 0 0
Other inflammatory or immune system disorders
Cardiovascular 0 0 0 0
Diseases of the vasculature and circulation including the lymphatic system

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Surgery - Ablation
Treatment: Drugs - Anti-arrhythmic Drugs (AADs)

Experimental: 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.

Active comparator: Anti-arrhythmic drugs (AAD) - 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.


Treatment: Surgery: Ablation
Catheter ablation (CA) will be performed in the standard fashion (described in international guidelines for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death from the AHA/ACC/HRS and the expert consensus statement on Catheter Ablation of Ventricular Arrhythmias from HRS/EHRA/APHRS/LAHRS). CA will be performed under conscious sedation or GA by an Electrophysiologist trained in cardiac arrhythmia ablation. CA will be guided by a combination of mapping techniques (standard practice), and described in guidelines for CA for VT. Mapping techniques will include pace, entrainment, activation, and electro-anatomic substrate mapping, where haemodynamically tolerated. Expected procedure duration is 3-6hrs.

Post-CA, AAD is stopped if patient was drug naïve pre-randomisation. The baseline type/dose of AAD pre-randomisation is continued if the patient was on an AAD pre-randomisation. Repeat ablations are permitted within 30-days post-randomisation.

Treatment: Drugs: Anti-arrhythmic Drugs (AADs)
Standard care usually encompasses patients who have not previously had AADs, being commenced on sotalol 80mg twice/day. Lower doses may be initiated by treating doctor, as clinically indicated. If there is contraindication to sotalol, another beta-blocker may be initiated using standard doses. Clinicians may consider alternative AADs if there is contraindication to beta-blockers. Doses would be up titrated to the maximal tolerated amount.

For patients already on an AAD, amiodarone would usually be added, as per VANISH trial.

They will receive a loading dose 400mg twice/day for 2 weeks, followed by 400mg/day for 4 weeks and 200mg/day thereafter. Patients who have "failed" amiodarone dose \<300mg/day will receive a repeat loading dose of 400mg twice/day for 2 weeks, followed by 400mg/day for 1 week, and 300mg/day thereafter.

If the treating doctor decides to do a CA for VT, the occurrence and timepoint of cross-over will be recorded. Cross-over is estimated to be \<2% (VANISH trial).
Intervention code [1] 0 0
Treatment: Surgery
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Composite of Recurrent VT or VT storm
Timepoint [1] 0 0
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.
Primary outcome [2] 0 0
Death
Timepoint [2] 0 0
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 outcome [1] 0 0
Recurrent sustained VT
Timepoint [1] 0 0
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.
Secondary outcome [2] 0 0
VT storm
Timepoint [2] 0 0
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.
Secondary outcome [3] 0 0
VT burden
Timepoint [3] 0 0
6 months after randomisation, with a 30-day treatment 'blanking' period after treatment initiation; and 6 months before randomisation
Secondary outcome [4] 0 0
Cardiovascular hospitalisation
Timepoint [4] 0 0
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.
Secondary outcome [5] 0 0
Mortality
Timepoint [5] 0 0
Outcome will be assessed at 3-, 6-, 12-, 18-, 24-, 30-, 36- months post-randomisation. Events will be included at any time after randomisation.
Secondary outcome [6] 0 0
Effect of intervention on ventricular function
Timepoint [6] 0 0
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.

Eligibility
Key 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.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key 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
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


The people assessing the outcomes
Intervention assignment
Parallel
Other design features
Phase
Not applicable
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
8/07/2020
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
30/06/2026
Actual
Sample size
Target
162
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
ACT,NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
The Canberra Hospital - Garran
Recruitment hospital [2] 0 0
Blacktown Hospital - Blacktown
Recruitment hospital [3] 0 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [4] 0 0
Nepean Hospital - Kingswood
Recruitment hospital [5] 0 0
John Hunter Hospital - New Lambton Heights
Recruitment hospital [6] 0 0
Royal North Shore Hospital - Saint Leonards
Recruitment hospital [7] 0 0
Westmead Hospital - Westmead
Recruitment hospital [8] 0 0
The Prince Charles Hospital - Chermside
Recruitment hospital [9] 0 0
Gold Coast University Hospital - Southport
Recruitment hospital [10] 0 0
Royal Adelaide Hospital - Adelaide
Recruitment hospital [11] 0 0
The Alfred Hospital - Melbourne
Recruitment hospital [12] 0 0
The Royal Melbourne Hospital - Parkville
Recruitment postcode(s) [1] 0 0
2605 - Garran
Recruitment postcode(s) [2] 0 0
2148 - Blacktown
Recruitment postcode(s) [3] 0 0
2050 - Camperdown
Recruitment postcode(s) [4] 0 0
2747 - Kingswood
Recruitment postcode(s) [5] 0 0
2305 - New Lambton Heights
Recruitment postcode(s) [6] 0 0
2065 - Saint Leonards
Recruitment postcode(s) [7] 0 0
2145 - Westmead
Recruitment postcode(s) [8] 0 0
4032 - Chermside
Recruitment postcode(s) [9] 0 0
4215 - Southport
Recruitment postcode(s) [10] 0 0
5000 - Adelaide
Recruitment postcode(s) [11] 0 0
3004 - Melbourne
Recruitment postcode(s) [12] 0 0
3050 - Parkville

Funding & Sponsors
Primary sponsor type
Other
Name
Western Sydney Local Health District
Address
Country

Ethics approval
Ethics application status

Summary
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.
Trial website
https://clinicaltrials.gov/study/NCT05524077
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Saurabh Kumar, MBBS, PhD
Address 0 0
Western Sydney Local Health District
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Saurabh Kumar, MBBS, PhD
Address 0 0
Country 0 0
Phone 0 0
+61288908140
Fax 0 0
Email 0 0
[email protected]
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT05524077