Back to resultsCatheter Ablation Versus Anti-arrhythmic Drugs for Ventricular Tachycardia (CAAD-VT)
Primary Purpose
Heart Disease Structural Disorder, Ventricular Tachycardia, Cardiomyopathy, Dilated
Status
Recruiting
Phase
Not Applicable
Locations
Australia
Study Type
Interventional
Intervention
Ablation
Anti-arrhythmic Drugs (AADs)
Sponsored by
About this trial
This is an interventional treatment trial for Heart Disease Structural Disorder
Eligibility Criteria
Inclusion Criteria:
Patients will be eligible for inclusion if they have:
≥1 prior episode of sustained VT in the prior 6 months;
- 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;
- 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;
- 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);
- 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;
- Aged ≥18 years.
Exclusion Criteria:
Patients will be excluded if they are:
- Unable or unwilling to provide informed consent or patients physician feels there is not significant equipoise to justify randomisation;
- Women who are pregnant, breast feeding;
- Medical illness with an anticipated life expectancy <3 months;
- Unable to complete study procedures or unwilling to be followed up;
- 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;
- Known channelopathy such as long QT, short QT, Brugada syndrome, catecholaminergic polymorphic VT;
- Known prior diagnosis of no structural heart disease, or idiopathic ventricular arrhythmia.
Sites / Locations
- The Canberra Hospital
- Blacktown HospitalRecruiting
- Royal Prince Alfred HospitalRecruiting
- Nepean HospitalRecruiting
- John Hunter HospitalRecruiting
- Royal North Shore HospitalRecruiting
- Westmead HospitalRecruiting
- The Prince Charles HospitalRecruiting
- Gold Coast University HospitalRecruiting
- Royal Adelaide HospitalRecruiting
- The Alfred HospitalRecruiting
- The Royal Melbourne Hospital
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Active Comparator
Arm Label
Ablation
Anti-arrhythmic drugs (AAD)
Arm Description
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.
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.
Outcomes
Primary Outcome Measures
Composite of Recurrent VT or VT storm
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
Death (at any time) due to any cause.
Secondary Outcome Measures
Recurrent sustained VT
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
Three or more documented episodes of VT within 24 hours or incessant VT
VT burden
VT burden (number of episodes of VT in the preceding 6 months compared to the 6 months after randomisation and therapy)
Cardiovascular hospitalisation
All cardiovascular hospitalisation; heart failure; hospitalisation for arrhythmia
Mortality
All-cause mortality; cardiovascular mortality; non-cardiac death
Effect of intervention on ventricular function
Effect of intervention on ventricular function as assessed by transthoracic echocardiography from baseline to 6-, 12-, 24- and 36-months' post intervention
Full Information
NCT ID
NCT05524077
First Posted
August 24, 2022
Last Updated
August 29, 2022
Sponsor
Western Sydney Local Health District
1. Study Identification
Unique Protocol Identification Number
NCT05524077
Brief Title
Catheter Ablation Versus Anti-arrhythmic Drugs for Ventricular Tachycardia
Acronym
CAAD-VT
Official Title
Catheter Ablation Versus Anti-arrhythmic Drugs for Ventricular Tachycardia (CAAD-VT): A Randomised Trial
Study Type
Interventional
2. Study Status
Record Verification Date
August 2022
Overall Recruitment Status
Recruiting
Study Start Date
July 8, 2020 (Actual)
Primary Completion Date
June 30, 2026 (Anticipated)
Study Completion Date
June 30, 2026 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Western Sydney Local Health District
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Disease Structural Disorder, Ventricular Tachycardia, Cardiomyopathy, Dilated, Sarcoidosis, Cardiomyopathy, Hypertrophic, Cardiomyopathy Ischemic, Cardiomyopathy, Familial, Arrhythmogenic Right Ventricular Cardiomyopathy 1, Arrhythmogenic Left Ventricular Cardiomyopathy
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Outcomes Assessor
Masking Description
Randomisation will be performed using a secure, password-protected web portal (REDCap) and the allocation sequence will be blinded to investigators and participants until the participants have been deemed eligible and enrolled in the study. It will not be possible to maintain blinding after study enrolment because the intervention is invasive.
Outcome verification will be blinded.
Allocation
Randomized
Enrollment
162 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Ablation
Arm Type
Experimental
Arm Description
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.
Arm Title
Anti-arrhythmic drugs (AAD)
Arm Type
Active Comparator
Arm Description
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.
Intervention Type
Procedure
Intervention Name(s)
Ablation
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
Anti-arrhythmic Drugs (AADs)
Intervention Description
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).
Primary Outcome Measure Information:
Title
Composite of Recurrent VT or VT storm
Description
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).
Time Frame
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.
Title
Death
Description
Death (at any time) due to any cause.
Time Frame
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 Measure Information:
Title
Recurrent sustained VT
Description
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)
Time Frame
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.
Title
VT storm
Description
Three or more documented episodes of VT within 24 hours or incessant VT
Time Frame
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.
Title
VT burden
Description
VT burden (number of episodes of VT in the preceding 6 months compared to the 6 months after randomisation and therapy)
Time Frame
6 months after randomisation, with a 30-day treatment 'blanking' period after treatment initiation; and 6 months before randomisation
Title
Cardiovascular hospitalisation
Description
All cardiovascular hospitalisation; heart failure; hospitalisation for arrhythmia
Time Frame
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.
Title
Mortality
Description
All-cause mortality; cardiovascular mortality; non-cardiac death
Time Frame
Outcome will be assessed at 3-, 6-, 12-, 18-, 24-, 30-, 36- months post-randomisation. Events will be included at any time after randomisation.
Title
Effect of intervention on ventricular function
Description
Effect of intervention on ventricular function as assessed by transthoracic echocardiography from baseline to 6-, 12-, 24- and 36-months' post intervention
Time Frame
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.
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients will be eligible for inclusion if they have:
≥1 prior episode of sustained VT in the prior 6 months;
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;
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;
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);
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;
Aged ≥18 years.
Exclusion Criteria:
Patients will be excluded if they are:
Unable or unwilling to provide informed consent or patients physician feels there is not significant equipoise to justify randomisation;
Women who are pregnant, breast feeding;
Medical illness with an anticipated life expectancy <3 months;
Unable to complete study procedures or unwilling to be followed up;
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;
Known channelopathy such as long QT, short QT, Brugada syndrome, catecholaminergic polymorphic VT;
Known prior diagnosis of no structural heart disease, or idiopathic ventricular arrhythmia.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Saurabh Kumar, MBBS, PhD
Phone
+61288908140
Email
saurabh.kumar@health.nsw.gov.au
First Name & Middle Initial & Last Name or Official Title & Degree
Timothy Campbell, BSc
Email
timothy.campbell@sydney.edu.au
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Saurabh Kumar, MBBS, PhD
Organizational Affiliation
Western Sydney Local Health District
Official's Role
Principal Investigator
Facility Information:
Facility Name
The Canberra Hospital
City
Garran
State/Province
Australian Capital Territory
ZIP/Postal Code
2605
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Rajeev Pathak, MBBS, PhD
First Name & Middle Initial & Last Name & Degree
Rajeev Pathak, MBBS, PhD
Facility Name
Blacktown Hospital
City
Blacktown
State/Province
New South Wales
ZIP/Postal Code
2148
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Pierre Qian, MBBS, PhD
First Name & Middle Initial & Last Name & Degree
Pierre Qian, MBBS, PhD
Facility Name
Royal Prince Alfred Hospital
City
Camperdown
State/Province
New South Wales
ZIP/Postal Code
2050
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kim Chan
First Name & Middle Initial & Last Name & Degree
Kim Chan, MBBS, PhD
Facility Name
Nepean Hospital
City
Kingswood
State/Province
New South Wales
ZIP/Postal Code
2747
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Ihab El-Sokkari, MBBCh
First Name & Middle Initial & Last Name & Degree
Ihab El-Sokkari, MBBCh
Facility Name
John Hunter Hospital
City
New Lambton Heights
State/Province
New South Wales
ZIP/Postal Code
2305
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nicholas Jackson, MBBS
First Name & Middle Initial & Last Name & Degree
Nicholas Jackson, MBBS
Facility Name
Royal North Shore Hospital
City
Saint Leonards
State/Province
New South Wales
ZIP/Postal Code
2065
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Karin Chia, MBBS, PhD
First Name & Middle Initial & Last Name & Degree
Karin Chia, MBBS, PhD
Facility Name
Westmead Hospital
City
Westmead
State/Province
New South Wales
ZIP/Postal Code
2145
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Saurabh Kumar, MBBS, PhD
First Name & Middle Initial & Last Name & Degree
Saurabh Kumar, MBBS, PhD
Facility Name
The Prince Charles Hospital
City
Chermside
State/Province
Queensland
ZIP/Postal Code
4032
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Haris Haqqani, MBBS, PhD
First Name & Middle Initial & Last Name & Degree
Haris Haqqani, MBBS, PhD
Facility Name
Gold Coast University Hospital
City
Southport
State/Province
Queensland
ZIP/Postal Code
4215
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Matthew Rowe, MBBS
First Name & Middle Initial & Last Name & Degree
Matthew Rowe, MBBS
Facility Name
Royal Adelaide Hospital
City
Adelaide
State/Province
South Australia
ZIP/Postal Code
5000
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kurt Roberts-Thomson, MBBS, PhD
First Name & Middle Initial & Last Name & Degree
Kurt Roberts-Thomson, MBBS, PhD
Facility Name
The Alfred Hospital
City
Melbourne
State/Province
Victoria
ZIP/Postal Code
3004
Country
Australia
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Peter Kistler, MBBS, PhD
First Name & Middle Initial & Last Name & Degree
Peter Kistler, MBBS, PhD
Facility Name
The Royal Melbourne Hospital
City
Parkville
State/Province
Victoria
ZIP/Postal Code
3050
Country
Australia
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Geoffrey Lee, MBChB, PhD
First Name & Middle Initial & Last Name & Degree
Geoffrey Lee, MBChB, PhD
12. IPD Sharing Statement
Plan to Share IPD
No
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Catheter Ablation Versus Anti-arrhythmic Drugs for Ventricular Tachycardia
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