Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000721404p
Ethics application status
Submitted, not yet approved
Date submitted
23/06/2025
Date registered
7/07/2025
Date last updated
7/07/2025
Date data sharing statement initially provided
7/07/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Catheter Ablation versus Anti-arrhythmic Drugs for Premature Ventricular Complexes (CAAD-PVC)
Scientific title
Catheter Ablation versus Anti-arrhythmic Drugs for Premature Ventricular Complexes (CAAD-PVC): A Randomised Controlled Trial
Secondary ID [1] 314723 0
Nil
Universal Trial Number (UTN)
U1111-1324-4474
Trial acronym
CAAD-PVC
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Premature ventricular complexes 337926 0
Condition category
Condition code
Cardiovascular 334250 334250 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Patients randomised to the intervention arm will be allocated to undergo the catheter ablation (CA) procedure, performed by a specialist cardiologist/electrophysiologist. This procedure typically lasts 2-4 hours and may be performed with the patient under sedation or general anesthesia, depending on the complexity of the patient. Patients will typically present to hospital the day of their porcdure and stay overnight following completion of the procedure.
Patients randomised to the intervention arm will be expected to have the CA procedure within 6 weeks post randomisation.
Medical therapy can be used as a temporising measure before CA, as is standard of care. If the patient is drug naïve, initiation of sotalol is recommended, but not mandated, as per the control arm. Post ablation, all PVC medial therapy should be discontinued.

Halting medical therapy for PVCs before a CA is standard practice: for patients already medicated for PVCs prior to CA, an additional multiday heart rhythm monitor may be performed after at least one week or 5 half-lives without any medical therapy to establish baseline burden.

CA procedures will be performed in the standard fashion, as accepted by international guidelines. Procedures will be performed under conscious sedation or general anaesthesia, The CA procedure requires venous and/or arterial femoral vascular access for the advancement electrode catheters to the coronary sinus, right ventricle and/or the left ventricle to aid identification of PVC site of origin. If the PVCs are arising from the left ventricle, access will be obtained via either transeptal puncture or retrograde aortic access at the operator's discretion.
Where available, pre-procedural imaging with cardiac MRI or cardiac CT will be integrated with the electroanatomic mapping system to aid procedures. Intracardiac echocardiography will be encouraged but not mandated.
Ablation will be guided by a combination of standard mapping techniques, as per standard practice. Preference will be given to “activation mapping” of the PVCs (which may be stimulated by administration of intravenous isoprenaline) using a three-dimensional electroanatomic mapping system. If there is paucity of PVCs, then “pace-mapping” will be performed.

End point of ablation will be abolition of all PVCs (with and without isoprenaline provocation) with a 30-minute waiting period.

Induction of ventricular tachycardia (VT) with programmed electrical stimulation (PES) will also be attempted during the procedure, as a standard practice to aid risk patient risk stratification. PES will be performed from the right ventricular apex, using a well validated stimulation protocol. A drive train of 400 ms will be used with each extra-stimulus introduced at 300 ms and decremented by 10ms until ventricular refractoriness. An additional extra-stimulus will then be added until all 4 extra-stimuli are refractory. PES will be accompanied by burst ventricular pacing and repeated with and without administration of isoprenaline.

Intravenous heparin will be given at the beginning (bolus) and during the procedure, especially if endocardial left ventricular access is planned to prevent risk of systemic and/or venous thromboembolism. Further heparin boluses are given to maintain an ACT >300s, as per published guidelines. If the patient is on anticoagulation, the procedure may be performed on uninterrupted warfarin and/or dabigatran, or bridging therapy with intravenous heparin or subcutaneous enoxaparin, as per the operator discretion. Post procedural anticoagulation for 6 weeks is recommended, but not mandated, if extensive ablation (RF time =10 minutes) is performed.

Post procedure, medical therapy (if patient was receiving it) is stopped. Repeat ablation procedures will be discouraged for the 6 months of monitoring.

Occasionally, patients may experience a random episode of PVC quiescence, leading to an absence of PVCs on the day of CA. This can be a result of changes in medication, stress, hormones, electrolytes and can be unpredictable. As at least one PVC occurring with the patient in the procedural area is required to perform a CA, an episode of PVC quiescence on the day of the procedure that inhibits the ablation from taking place will not preclude the patient from having a repeat attempt at the CA.

Procedural reports, medical notes and admission records will bu used to monitor adherence to the intervention.
Intervention code [1] 331327 0
Treatment: Surgery
Comparator / control treatment
Patients randomised to the control arm will be managed with medical therapy alone by their usual medical practitioners. The objective of this arm is that it replicates what would constitute standard of care for patients with PVCs managed with a non-interventional approach.

Standard clinical care would usually encompass patients who have symptoms and have not previously been prescribed an AAD or BB, being commenced on an AAD and/or a BB. Choice of AAD/BB will be left to primary physician however if this is deferred to the trial team, clinical protocol would suggest sotalol 80mg twice daily – a commonly medication that has both AAD and BB properties. A lower dose may be initiated by the treating physician, as clinically indicated.

If there is contraindication to sotalol, an alternative BB may be initiated using standard doses e.g. metoprolol, atenolol, bisoprolol, carvedilol. Clinicians may consider alternative AAD if there is a contraindication to a b-blocker. For example, a dihydropyridine calcium channel blocker e.g. verapamil or diltiazem may be initiated if patient has concurrent asthma. If coronary artery disease and structural heart disease is ruled out, flecainide (class I anti-arrhythmic agent) can also be used.

The duration of the treatment will be for a minimum of three months.
As with clinical practice, medical therapy (AAD/BB) can be changed at any time depending on clinical response.
Adherence will be monitored with a medication diary.
Control group
Active

Outcomes
Primary outcome [1] 341912 0
Difference in PVC burden following treatment, compared to pre-treatment
Timepoint [1] 341912 0
Baseline and 3 months post commencement of treatment (i.e. from initiation of medical therapy or completion of catheter ablation procedure)
Secondary outcome [1] 448972 0
Tolerability of medical therapy (adherence, adverse events, patient satisfaction). This will be assessed as a composite outcome. Adverse events related to medication will include known adverse side effects including the below, Sotalol o Heart failure o Torsades de pointes o Symptomatic bradycardia o Fatigue o Rash o Intolerable gastrointestinal disturbances namely nausea, vomiting, indigestion, flatulence, cramps, diarrhoea, constipation, ulceration o Intolerable sensory disturbances namely paraesthesia, visual changes, taste or hearing abnormalities, abnormal physical weakness or lack of energy o Intolerable central nervous system effects including sleep changes, depression, mood changes, anxiety o Sexual dysfunction including reduce libido or impotence
Timepoint [1] 448972 0
Baseline and 6 months post commencement of treatment (i.e. from initiation of medical therapy or completion of catheter ablation procedure)
Secondary outcome [2] 448969 0
Effect of treatment on ventricular function including of left ventricular ejection fraction (LVEF) and global longitudinal strain (GLS), assessed as a composite outcome.
Timepoint [2] 448969 0
Baseline and 6 months post commencement of treatment (i.e. from initiation of medical therapy or completion of catheter ablation procedure)
Secondary outcome [3] 448970 0
Quality of Life score as measured by QoL questionnaires, including the Arrhythmia-Specific questionnaire in Tachycardia and Arrhythmia (ASTA) questionnaire
Timepoint [3] 448970 0
Baseline and 6 months post commencement of treatment (i.e. from initiation of medical therapy or completion of catheter ablation procedure)
Secondary outcome [4] 448973 0
Tolerability of catheter ablation (complications, adverse events, patient satisfaction), Assessed as composite outcome. Complications related to catheter ablation include: • Major vascular injury (requiring surgical repair or a blood transfusion > 1 unit of packed cells) • Thromboembolism • Stroke or transient ischaemic attack • Deep vein thrombosis • Embolism to limb or peripheral organs • Cardiac bleeding • Tamponade requiring percutaneous or surgical drainage • Valve injury • New onset valvular regurgitation in follow -up • Damage to the conducting system • Temporary or permanent complete heart block • Myocardial ischaemia or infarction defined by rise and fall of cardiac biomarkers with one of: o Symptoms of ischaemia, o New ST changes or new LBBB, o Development of Q waves o Evidence on imaging of new loss of viable myocardium or new regional wall motion abnormality • Acute heart failure occurring within 48 hours of catheter ablation • Complications of epicardial access and/or ablation • Pericardial bleeding • Injury to subdiaphragmatic vessels or organs • Coronary artery injury • Phrenic nerve injury • Severe pericarditis or pleuritic pain requiring hospitalisation >72 hours
Timepoint [4] 448973 0
Baseline and 6 months post commencement of treatment (i.e. from initiation of medical therapy or completion of catheter ablation procedure).
Secondary outcome [5] 448968 0
Overall PVC burden
Timepoint [5] 448968 0
Baseline and 3 months, 6 months and 12 months post commencement of treatment (i.e. from initiation of medical therapy or completion of catheter ablation procedure)
Secondary outcome [6] 448971 0
Number of patients with greater than or equal to each of 75%, 90% and 95% reduction in burden. This will be assessed as a composite outcome.
Timepoint [6] 448971 0
Baseline and 3 months, 6 months and 12 months post commencement of treatment (i.e. from initiation of medical therapy or completion of catheter ablation procedure)
Secondary outcome [7] 448975 0
Health service utilization (cardiovascular hospital admissions or consultations). This will be assessed as a composite outcome.
Timepoint [7] 448975 0
Baseline and 6 months post commencement of treatment (i.e. from initiation of medical therapy or completion of catheter ablation procedure).

Eligibility
Key inclusion criteria
1. PVC burden of greater than or equal to 10% as determined by multiday (>24-hour) heart rhythm monitoring,
2. Normal left ventricular ejection fraction
3. Aged 18 years or older.
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Unable or unwilling to provide informed consent or comply with study requirements including study investigations and follow-up, medical adherence, completion of intervention.
2. Women who are pregnant or breast feeding.
3. Life expectancy at least 12 months.
4. Ventricular tachycardia (VT) that is inducible greater than or equal to 10 seconds, spontaneous greater than or equal to 30 seconds or not haemodynamically tolerated) or greater than or equal to 10 episodes of non-sustained ventricular tachycardia (defined as >5 sequential beats, greater than or equal to 10 seconds) in 24 hrs during ambulatory heart rhythm recording.
5. Structural heart disease including clinically significant coronary artery, valvular disease or clinically significant myocardial replacement.
6. Known cardiac channelopathies (e.g. Catecholaminergic polymorphic ventricular tachycardia (CPVT), long- or short QT syndrome, Brugada syndrome).
7. Responsible primary care or other responsible physician believes it is not appropriate to participate in the study or unable to complete the study procedures, e.g. concomitant illness, physical impairment or mental condition which could interfere with the conduct of the study including outcome assessments.

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)
Allocation not concealed
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software 1:1 in block sizes of 2-6
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/10/2025
Actual
Date of last participant enrolment
Anticipated
1/04/2027
Actual
Date of last data collection
Anticipated
1/04/2028
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 28139 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 44345 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 319277 0
Government body
Name [1] 319277 0
NHMRC
Country [1] 319277 0
Australia
Primary sponsor type
Government body
Name
Western Sydney Local Health District
Address
Country
Australia
Secondary sponsor category [1] 321748 0
None
Name [1] 321748 0
Address [1] 321748 0
Country [1] 321748 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 317852 0
Western Sydney Local Health District Human Research Ethics Committee
Ethics committee address [1] 317852 0
Ethics committee country [1] 317852 0
Australia
Date submitted for ethics approval [1] 317852 0
25/06/2025
Approval date [1] 317852 0
Ethics approval number [1] 317852 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 142362 0
A/Prof Saurabh Kumar
Address 142362 0
Westmead Hospital, Corner Hawkesbury Road and Darcy Road, Westmead NSW 2145
Country 142362 0
Australia
Phone 142362 0
+612 88908981
Fax 142362 0
Email 142362 0
[email protected]
Contact person for public queries
Name 142363 0
Saurabh Kumar
Address 142363 0
Westmead Hospital, Corner Hawkesbury Road and Darcy Road, Westmead NSW 2145
Country 142363 0
Australia
Phone 142363 0
+61 288908981
Fax 142363 0
Email 142363 0
[email protected]
Contact person for scientific queries
Name 142364 0
Saurabh Kumar
Address 142364 0
Westmead Hospital, Corner Hawkesbury Road and Darcy Road, Westmead NSW 2145
Country 142364 0
Australia
Phone 142364 0
+61 288908981
Fax 142364 0
Email 142364 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
Yes
Will there be any conditions when requesting access to individual participant data?
Persons/groups eligible to request access:
• Researchers
Conditions for requesting access:
• Yes, conditions apply:
• Requires review on a case-by-case basis by the trial custodian, sponsor or data sharing committee
• Requires a scientifically sound proposal or protocol
• Requires approval by an ethics committee
• Requires a data sharing agreement between data requester and trial custodian or sponsor
What individual participant data might be shared?
• De-identified individual participant data:
• Published results
• Primary outcome(s)
• Safety data
What types of analyses could be done with individual participant data?
• Systematic reviews and meta-analyses
• Studies exploring new research questions
• Health economic analyses
• Studies testing whether findings can be repeated or confirmed
• Teaching research methods or developing new statistical techniques
When can requests for individual participant data be made (start and end dates)?
From:
After publication of main results
To:
Not yet decided
Where can requests to access individual participant data be made, or data be obtained directly?
• Email of trial custodian, sponsor or committee: [email protected]

Are there extra considerations when requesting access to individual participant data?
Yes: Instuitional policies



What supporting documents are/will be available?

No Supporting Document Provided


Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.