Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12625000466448p
Ethics application status
Submitted, not yet approved
Date submitted
25/11/2024
Date registered
16/05/2025
Date last updated
16/05/2025
Date data sharing statement initially provided
16/05/2025
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomized trial of medical therapy versus conduction system pacing with atrioventricular (AV) node ablation in persistent atrial fibrillation (AF) and heart failure with preserved ejection fraction
Scientific title
Randomized trial of medical therapy versus conduction system pacing with AV node ablation in persistent atrial fibrillation (AF) and heart failure with preserved ejection fraction (HFpEF)- the STALL HFpEF II Study
Secondary ID [1] 313461 0
Nil known
Universal Trial Number (UTN)
Trial acronym
STALL HFpEF II
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Atrial fibrillation 335862 0
Heart Failure with preserved ejection fraction 335863 0
Condition category
Condition code
Cardiovascular 332447 332447 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Details of the study will be thoroughly explained in the patient information and consent form (PICF) given to potential participants, and participants will be required to provide consent prior to participating. Participants randomised to the intervention arm will undergo conduction system pacing, followed by atrioventricular (AV) node ablation 4 weeks later. Conduction system pacing will be performed by pacing cardiologists and would typically be around 1 hour in duration under sedation.

Conduction system pacing in this study will be based on left bundle branch area pacing (LBBAP). For this study only the lumenless lead (Medtronic 3830 lead) will be utilized. In brief, the LBBAP lead is positioned on the RV septum within a guiding sheath. Determination of a suitable catheter position is based on anyone of the following techniques: a) Detection of a His potential and advancing the sheath 15–20 mm towards the RV apex in RAO 30 view ; b) Use the tricuspid valve summit as an anatomical marker (which approximates His bundle position), and advancing the sheath 15–20 mm towards the RV apex in RAO 30 view ; c) Divide the septum into 9 sectors in RAO 30 view and targeting the mid section

Once the catheter is in position, the LBBAP lead is exposed in contact with the right side of the septum and connected in a unipolar configuration to the PSA recording. A suitable site for lead penetration is based on the demonstration of a ‘W’ pattern on the paced QRS morphology in V1, along with discordant paced QRS morphologies in leads II and III. The lead is subsequent screwed into the septum with rapid continuous rotations.

Lead depth during rotations can be determined by one/more of the following techniques
a) Fluoroscopy in LAO 30–40° view ; b) Paced QRS morphology in unipolar mode - as the lead progresses from the right side to the left side of the septum, the QRS becomes narrower, terminal R wave appears in V1, and the V6RWPT progressively shortens ; c) Premature ventricular complexes provoked by mechanical trauma ; d) Lead impedance - this usually rises initially and then falls as the lead approaches the LV endocardium; e) Myocardial current of injury (COI) -the COI rises initially but decreases as the lead reaches the LV subendocardial area to an average of approximately 10–12 mV

LBB capture is confirmed by the presence of one/more of the following parameters:
a) Left ventricular activation time (LVAT) of 44 ms ; d) Left bundle branch potential-V6RWPT interval = pacing stimulus-V6RWPT interval (+/-10ms)

AV node ablation will be done by electrophysiologists, which is done with non -irrigated ablation catheters at 50W power setting. The AV node ablation would typically be around 30 minutes in duration and done under sedation. The procedures will be done in person at the time of procedure. All participants in the intervention arm will be followed up for 12 months.. All participants will undergo clinical reviews at 3 months, 6 months and 12 months.
Intervention code [1] 330034 0
Treatment: Devices
Comparator / control treatment
Patients randomised to medical arm will receive optimal medical therapy to achieve adequate rate control of atrial fibrillation, and euvolaemic status with diuretics. Rate control of heart rate will be achieved usinng AV node controllers including beta blockers, calcium channel blockers and /or digoxin. All participants in the medical arm will be followed up for 12 months..Participants will undergo 24 hour Holter monitors at baseline, 3 months, 6 months and 12 months to ensure AF rate control. Clinical reviews will also be done at 3 months, 6 months and 12 months.
Control group
Active

Outcomes
Primary outcome [1] 339988 0
change in peak exercise pulmonary capillary wedge pressure from baseline to 12 months
Timepoint [1] 339988 0
All participants will undergo exercise right heart catheterization at baseline and 12 months from time of study recruitment
Secondary outcome [1] 442228 0
Changes in quality of life (QOL) questionnaire scores at 12 months
Timepoint [1] 442228 0
All participants will undertake QOL assessments at baseline and 12 months from time of study recruitment
Secondary outcome [2] 442229 0
Echocardiographic measures will be assessed as a composite secondary outcome. The parameters to be included LA size (mm) LA indexed volume (ml/m2) LA strain LV assessment LVESD, LVEDD (mm) Ejection fraction (%) Global longitudinal strain (%) Diastolic function E velocity E/a ratio (if in sinus) E/e’ Pulmonary venous S/D ratio TR velocity /PASP
Timepoint [2] 442229 0
All participants will have echocardiograms to assess changes in parameters at baseline and 12 months from time of study recruitment
Secondary outcome [3] 442230 0
Change in natriuretic peptide levels at 12 months
Timepoint [3] 442230 0
All participants will have natriuretic peptide levels checked at baseline and 12 months from time of study recruitment

Eligibility
Key inclusion criteria
1. Patients with HFpEF based on the 2021 European Society Cardiology(ESC) guidelines
• Symptoms and signs of heart failure
• Preserved left ventricular ejection fraction (LVEF greater than or equal to 50%); and
• Objective evidence of cardiac structural and/or functional abnormalities consistent with the presence of LV diastolic dysfunction/raised LV filling pressures, including raised natriuretic peptides
2. Patients aged equal or more than 18 years old
3. Patients with permanent AF who are not deemed suitable candidate for an AF ablation procedure
4. Patients must be able and willing to provide written informed consent to participate in this investigation
5. Patients must be willing and able to comply with all peri-ablation and follow- up requirements
Minimum age
18 Years
Maximum age
85 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Patients for whom rhythm control will be attempted/pursued
2. Patients with AF felt to be secondary to an obvious reversible cause
3. Patients with contraindications to systemic anticoagulation with heparin or coumadin or a direct thrombin inhibitor
4. Pregnancy
5. Ejection fraction of <50% on echocardiogram
6. Severe, non-revascularised coronary artery disease (percutaneous coronary intervention permissible)
7. Severe pulmonary disease
8. Severe valvular heart disease or cyanotic congenital heart disease
9. Severe frailty (Clinical Frailty Scale greater than or equal to 7 or comorbidity reducing life expectancy to 40)
15. Patient inability to consent

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)
sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Alfred clinical trials pharmacy (Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
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
26/05/2025
Actual
Date of last participant enrolment
Anticipated
31/12/2025
Actual
Date of last data collection
Anticipated
31/12/2026
Actual
Sample size
Target
40
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 27363 0
The Alfred - Melbourne
Recruitment postcode(s) [1] 43454 0
3004 - Melbourne

Funding & Sponsors
Funding source category [1] 317897 0
Charities/Societies/Foundations
Name [1] 317897 0
National Heart Foundation
Country [1] 317897 0
Australia
Primary sponsor type
Hospital
Name
The Alfred Hospital
Address
Country
Australia
Secondary sponsor category [1] 320241 0
None
Name [1] 320241 0
Address [1] 320241 0
Country [1] 320241 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 316586 0
Alfred Hospital Ethics Committee
Ethics committee address [1] 316586 0
Ethics committee country [1] 316586 0
Australia
Date submitted for ethics approval [1] 316586 0
05/12/2024
Approval date [1] 316586 0
Ethics approval number [1] 316586 0

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

Contacts
Principal investigator
Name 138326 0
Prof David Kaye
Address 138326 0
Alfred Health, 55 Commercial Road, Melbourne, Victoria 3004
Country 138326 0
Australia
Phone 138326 0
+61 0390763263
Fax 138326 0
Email 138326 0
[email protected]
Contact person for public queries
Name 138327 0
Dr David Chieng
Address 138327 0
Alfred Health, 55 Commercial Road, Melbourne, Victoria 3004
Country 138327 0
Australia
Phone 138327 0
+61 0390763263
Fax 138327 0
Email 138327 0
[email protected]
Contact person for scientific queries
Name 138328 0
Dr David Chieng
Address 138328 0
Alfred health, 55 Commercial Road, Melbourne, Victoria 3004
Country 138328 0
Australia
Phone 138328 0
+61 0390763263
Fax 138328 0
Email 138328 0
[email protected]

Data sharing statement
Will the study consider sharing individual participant data?
No


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.