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Trial registered on ANZCTR

Registration number

ACTRN12625000712404

Ethics application status

Approved

Date submitted

1/05/2025

Date registered

4/07/2025

Date last updated

4/07/2025

Date data sharing statement initially provided

4/07/2025

Type of registration

Prospectively registered

Titles & IDs

Public title

Testing a Pacemaker Upgrade: A Study of Left Bundle Branch Area Pacing (a Newer Heart Pacing Method) for Heart Failure Patients Whose Current Pacemaker Isn't Helping Enough

Scientific title

A Feasibility Study of Left Bundle Branch Area Pacing Upgrade for Cardiac Resynchronisation Therapy Patients who are Non-Responsive: Assessing Recruitment Feasibility, Procedural Feasibility, and Follow-up Adherence.

Secondary ID [1]

None

Universal Trial Number (UTN)

Trial acronym

UPGRADE-CRT

Linked study record

Health condition

Health condition(s) or problem(s) studied:

Heart Failure

Shortness of Breath

Condition category

Condition code

Cardiovascular

Other cardiovascular diseases

Intervention/exposure

Study type

Interventional

Description of intervention(s) / exposure

The Left Bundle Branch Area Pacing (LBBAP) intervention for this study involves:

What it involves for participants: Participants will undergo a further surgical procedure to upgrade their existing Cardiac Resynchronisation Therapy (CRT) pacemaker system. This involves a specialist heart doctor (electrophysiologist) implanting a new, thin pacing wire (lead, specifically a Medtronic 3830 model) into a precise location in the heart muscle (the interventricular septum, aiming for the left bundle branch area). This is done via a vein, typically under the collarbone, using X-ray guidance. The existing wire in the heart's vein (coronary sinus lead) will then be disconnected from the pacemaker device, and the new LBBAP lead will be connected. This is not an external modification; it is an invasive surgical upgrade to their implanted device.
Frequency/duration of the intervention: The LBBAP upgrade procedure is a one-time surgical event. While the protocol doesn't specify an exact duration for the surgery itself (it's listed as a procedural success metric to be recorded), such procedures typically last one hour. Once the new lead is implanted and functioning, the LBBAP is continuous. Participants will then be followed up for observation and data collection at scheduled visits (2 months, 6 months, and 12 months post-procedure).
Who will be administering the intervention: The LBBAP upgrade procedure will be performed by Staff Specialist Electrophysiologists (cardiologists specializing in heart rhythm disorders) at the participating study hospitals.
Standardized or individualized protocol: All participants will undergo the same LBBAP upgrade procedure with the goal of achieving effective pacing from the left bundle branch area. However, the precise final position of the new pacing lead within the heart's septum, and the electrical settings used to confirm optimal LBBAP capture (like sensing, pacing thresholds, and QRS morphology/duration), will be individualized for each participant during the procedure to ensure the best possible physiological pacing based on their specific anatomy and cardiac electrical activity.
Monitoring adherence to the intervention: Adherence to the LBBAP intervention (meaning the LBBAP system is implanted and functioning as intended to provide pacing) is monitored through regular device interrogations at follow-up visits. These interrogations allow the study team to check the LBBAP lead's parameters (e.g., stability, electrical measurements) and confirm ongoing effective pacing, thus ensuring the intervention is being delivered as planned.

Intervention code [1]

Treatment: Devices

Comparator / control treatment

1. Clarification of the "Control" Statement:

This study uses a pre-post interventional design where each participant acts as their own control. Key clinical outcome measures (such as left ventricular ejection fraction, left ventricular end systolic volume, quality of life scores via KCCQ-12, NYHA functional class, and BNP levels) along with data on hospitalisations for heart failure, will be collected from participants before they undergo the Left Bundle Branch Area Pacing (LBBAP) upgrade procedure. These pre-intervention baseline data will then be compared to the same measures collected at scheduled follow-up points (at 2, 6, and 12 months) after the LBBAP upgrade has been implemented. The 'control' period effectively represents each participant's status and outcomes while on their existing, optimized conventional Cardiac Resynchronisation Therapy (CRT) prior to receiving the LBBAP intervention.

2. Time Period for 'Control' Data Collection:

The 'control' data, representing the participant's status prior to the LBBAP intervention, is collected over several defined periods:

Participants must have had their existing conventional Cardiac Resynchronisation Therapy (CRT) device for at least 6 months before enrollment, and their non-response to this therapy is confirmed based on assessments made after this minimum 6-month period on CRT.
Specific baseline measures for the LBBAP upgrade study (including echocardiogram, KCCQ-12, NYHA class, BNP levels, and device interrogation data from their existing CRT) are collected during the pre-procedure/enrollment phase, typically within 30 days before the LBBAP upgrade. An existing echocardiogram may be used for baseline if performed within the 3 months prior to the LBBAP procedure.
Prior to collecting these LBBAP study baseline measures, the participant's existing CRT device settings are reviewed and optimized if necessary. This ensures the pre-intervention 'control' data reflects their best achievable state on conventional CRT.
For certain historical data, such as the number of hospitalisations for heart failure, information will be collected pertaining to the period since their original CRT implantation and prior to the LBBAP upgrade. This timeframe will vary per participant but will be at least 6 months.

Control group

Active

Outcomes

Primary outcome [1]

Recruitment Feasibility

Timepoint [1]

Baseline Assessments: Conducted "Within 30 days prior to the Left Bundle Branch Area Pacing (LBBAP) upgrade procedure (intervention commencement)." This period includes eligibility screening, informed consent, and collection of all baseline clinical data, questionnaires, and biological samples as specified in the protocol. Immediate Post-Intervention Assessments: Conducted "Within 24 hours following completion of the LBBAP upgrade procedure.". Pre-Discharge Assessments: Conducted "Prior to hospital discharge, typically between 0 and 7 days after the LBBAP upgrade procedure.". 2-Month Follow-up: Conducted "At 2 months (with a window of ± 14 days) post-LBBAP upgrade procedure commencement.". 6-Month Follow-up: Conducted "At 6 months (with a window of ± 15 days) post-LBBAP upgrade procedure commencement.". 12-Month Follow-up / End of Study Treatment: Conducted "At 12 months (with a window of ± 30 days) post-LBBAP upgrade procedure commencement." This visit also serves as the End of Treatment (EOT) assessment

Primary outcome [2]

Procedural Feasibility

Timepoint [2]

The outcomes for procedural feasibility are assessed and data are collected at timepoints directly related to the LBBAP upgrade procedure (intervention commencement) for each participant within the 24 hour peri-procedural window. Any intra-procedural adverse events are also recorded at this time. Intra-procedural Feasibility Metrics: Data such as procedure completion status, total procedure duration, fluoroscopy time, success in achieving Left Bundle Branch (LBB) capture (e.g., target QRS duration, paced Left Ventricular Activation Time (pLVAT), ECG characteristics), and initial lead stability parameters (pacing thresholds, R-wave amplitude, impedance) will be recorded during the actual LBBAP upgrade procedure for each participant.

Primary outcome [3]

Follow-Up Adherence

Timepoint [3]

Assessment of follow-up adherence (defined as participants' compliance with scheduled visits and data collection protocols) is determined at the following key timepoints: 2-Month Follow-up Visit: Adherence is assessed based on attendance and completion of required study procedures at the visit scheduled "At 2 months (with a window of ± 14 days) post-LBBAP upgrade procedure commencement". 6-Month Follow-up Visit: Adherence is assessed based on attendance and completion of required study procedures at the visit scheduled "At 6 months (with a window of ± 15 days) post-LBBAP upgrade procedure commencement". 12-Month Follow-up / End of Study Treatment Visit: Adherence is assessed based on attendance and completion of required study procedures at the visit scheduled "At 12 months (with a window of ± 30 days) post-LBBAP upgrade procedure commencement". The successful completion of these scheduled visits and the data collection protocols therein form the basis for evaluating the 'follow-up adherence' feasibility outcome

Secondary outcome [1]

Left Ventricular Ejection Fraction

Timepoint [1]

For the secondary outcome LVEF (Left Ventricular Ejection Fraction), the timepoints for assessment are anchored relative to the participant and the LBBAP intervention as follows: Baseline LVEF: Assessed via echocardiogram "Within 30 days prior to the Left Bundle Branch Area Pacing (LBBAP) upgrade procedure (intervention commencement)." The protocol also notes that an echocardiogram performed within the 3 months prior to this pre-procedure window may be used as the baseline measurement. 6-Month Post-Intervention LVEF: Assessed via echocardiogram "At 6 months (with a window of ± 15 days) post-LBBAP upgrade procedure commencement". 12-Month Post-Intervention LVEF: Assessed via echocardiogram "At 12 months (with a window of ± 30 days) post-LBBAP upgrade procedure commencement". These timepoints will allow for the assessment of change in LVEF from baseline to the 6 and 12-month follow-up points after the LBBAP intervention

Secondary outcome [2]

Left Ventricular End-Systolic Volume

Timepoint [2]

For the secondary outcome LVESV (Left Ventricular End Systolic Volume), the timepoints for assessment are anchored relative to the participant and the LBBAP intervention as follows: Baseline LVESV: Assessed via echocardiogram "Within 30 days prior to the Left Bundle Branch Area Pacing (LBBAP) upgrade procedure (intervention commencement)." The protocol also indicates that an echocardiogram performed within the 3 months prior to this pre-procedure window may be used as the baseline measurement. 6-Month Post-Intervention LVESV: Assessed via echocardiogram "At 6 months (with a window of ± 15 days) post-LBBAP upgrade procedure commencement". 12-Month Post-Intervention LVESV: Assessed via echocardiogram "At 12 months (with a window of ± 30 days) post-LBBAP upgrade procedure commencement". These timepoints will allow for the assessment of change in LVESV from baseline to the 6 and 12-month follow-up points after the LBBAP intervention

Secondary outcome [3]

Quality of Life

Timepoint [3]

For the secondary outcome of quality of life, assessed using the KCCQ-12 (Kansas City Cardiomyopathy Questionnaire), the timepoints for assessment are anchored relative to the participant and the LBBAP intervention as follows: Baseline KCCQ-12: The KCCQ-12 questionnaire is administered "Within 30 days prior to the Left Bundle Branch Area Pacing (LBBAP) upgrade procedure (intervention commencement)". 6-Month Post-Intervention KCCQ-12: The KCCQ-12 questionnaire is administered "At 6 months (with a window of ± 15 days) post-LBBAP upgrade procedure commencement". 12-Month Post-Intervention KCCQ-12: The KCCQ-12 questionnaire is administered "At 12 months (with a window of ± 30 days) post-LBBAP upgrade procedure commencement". These timepoints will allow for the assessment of change in quality of life from baseline to the 6 and 12-month follow-up points after the LBBAP intervention

Secondary outcome [4]

New York Heart Association Class (NYHA Class)

Timepoint [4]

For the secondary outcome of New York Heart Association (NYHA) class, the timepoints for assessment are anchored relative to the participant and the LBBAP intervention as follows: Baseline NYHA Class: Assessed "Within 30 days prior to the Left Bundle Branch Area Pacing (LBBAP) upgrade procedure (intervention commencement)". 6-Month Post-Intervention NYHA Class: Assessed "At 6 months (with a window of ± 15 days) post-LBBAP upgrade procedure commencement". 12-Month Post-Intervention NYHA Class: Assessed "At 12 months (with a window of ± 30 days) post-LBBAP upgrade procedure commencement". These timepoints will allow for the assessment of change in NYHA class from baseline to the 6 and 12-month follow-up points after the LBBAP intervention

Secondary outcome [5]

Brain natriuretic peptide (BNP)

Timepoint [5]

For the secondary outcome specifically of BNP (Brain Natriuretic Peptide) levels, the timepoints for assessment are anchored relative to the participant and the LBBAP intervention as follows: Baseline BNP: Collected "Within 30 days prior to the Left Bundle Branch Area Pacing (LBBAP) upgrade procedure (intervention commencement)". 6-Month Post-Intervention BNP: Collected "At 6 months (with a window of ± 15 days) post-LBBAP upgrade procedure commencement". 12-Month Post-Intervention BNP: Collected "At 12 months (with a window of ± 30 days) post-LBBAP upgrade procedure commencement". These timepoints will allow for the assessment of change in BNP levels from baseline to the 6 and 12-month follow-up points after the LBBAP intervention

Secondary outcome [6]

Atrial Fibrillation Burden

Timepoint [6]

For the secondary outcome of atrial fibrillation (AF) burden, which is assessed by interrogation of cardiac device data, the timepoints for assessment are anchored relative to the participant and the LBBAP intervention as follows: Baseline AF Burden: Assessed via cardiac device interrogation "Within 30 days prior to the Left Bundle Branch Area Pacing (LBBAP) upgrade procedure (intervention commencement)." This interrogation will review the AF burden recorded by the participant's existing CRT device before the upgrade. 6-Month Post-Intervention AF Burden: Assessed via cardiac device interrogation "At 6 months (with a window of ± 15 days) post-LBBAP upgrade procedure commencement". 12-Month Post-Intervention AF Burden: Assessed via cardiac device interrogation "At 12 months (with a window of ± 30 days) post-LBBAP upgrade procedure commencement". While device interrogations (which collect AF burden data) also occur at pre-discharge and at the 2-month follow-up visit, the formal secondary outcome analysis for change in AF burden, as stated in the protocol, focuses on the baseline, 6-month, and 12-month timepoints

Secondary outcome [7]

Hospitalisation for Heart Failure

Timepoint [7]

Data on hospitalisations for heart failure will be collected for two main periods: Pre-Intervention Period: Information is gathered for hospitalisations occurring from the participant's original Cardiac Resynchronisation Therapy (CRT) implantation date up to the day before the Left Bundle Branch Area Pacing (LBBAP) upgrade procedure (intervention commencement). Post-Intervention Period: Information is gathered for hospitalisations occurring from the day of the LBBAP upgrade procedure (intervention commencement) throughout the 12-month study follow-up. This information is actively collected at scheduled follow-up visits, which occur at 2 months (±14 days), 6 months (±15 days), and 12 months (±30 days) post-LBBAP upgrade procedure commencement

Secondary outcome [8]

Procedural Complications

Timepoint [8]

During the LBBAP procedure, within 24 hours post-procedure, and up to pre-discharge (0-7 days post-LBBAP upgrade procedure commencement)

Secondary outcome [9]

Worsening Left Ventricular Ejection Fraction (LVEF) >10% post-intervention

Timepoint [9]

LVEF assessed at Baseline (within 30 days prior to LBBAP upgrade procedure commencement or using an echo from the prior 3 months), then at 6 months (±15 days) and 12 months (±30 days) post-LBBAP upgrade procedure commencement

Secondary outcome [10]

Worsening of New York Heart Association (NYHA) Class post-intervention

Timepoint [10]

NYHA Class assessed at Baseline (within 30 days prior to LBBAP upgrade procedure commencement), then at 6 months (±15 days) and 12 months (±30 days) post-LBBAP upgrade procedure commencement

Secondary outcome [11]

Requirement for LBBAP lead repositioning

Timepoint [11]

Assessed at the time of LBBAP procedure, immediate post-procedure period (<24 hours, pre-discharge 0-7 days), and at all scheduled follow-up device interrogations (2 months ±14 days, 6 months ±15 days, and 12 months ±30 days post-LBBAP upgrade procedure commencement), or if clinically indicated between visits

Secondary outcome [12]

Requirement for LBBAP lead removal

Timepoint [12]

Eligibility

Key inclusion criteria

1. Patients with Heart Failure with reduced Ejection Fraction (HFrEF) with existing Cardiac Resynchronisation Therapy (CRT) who are at least 6 months post-implant and are showing signs of CRT non-response.
2. CRT (Defibrillator or Pacemaker) of greater than or equal to 6 months duration
3. New York Heart Association (NYHA) class II-IV symptoms
4. Native QRS width of 150-180ms and Left Bundle Branch Block (LBBB)
5. Greater than or equal to 90% Biventricular (BiV) pacing
6. Ejection Fraction (EF) less than or equal to 35% and improvement from baseline EF less than or equal to 10% post CRT implant after at least 6 months

Minimum age

18 Years

Maximum age

No limit

Sex

Both males and females

Can healthy volunteers participate?

Key exclusion criteria

Cognitive impairment: Defined as diagnosed cognitive disorders such as dementia or other neurodegenerative diseases, or a history of stroke or traumatic brain injury resulting in low scores on cognitive tests like the Mini-Mental State Examination (MMSE) (scores within the range of 19 to 23 inclusive, out of 30) or Montreal Cognitive Assessment (MoCA) (scores within the range of 18 to 25 inclusive, out of 30). Also includes significant functional impairments in daily living due to cognitive deficits from severe psychiatric disorders.

Chronic infection: (This is a major contraindication to cardiac device insertion).

Metastatic cancer: (This is likely to confound the validity of the primary outcome and is likely to negatively affect wound healing and the safety of the upgrade procedure).

Patients with a prognosis of less than 12 months will be excluded given the 12-month enrolment period of the study.

Patients with New York Heart Association (NYHA) Class I symptoms will be excluded as they are unlikely to have Cardiac Resynchronisation Therapy (CRT) non-response by definition and cannot see improvement with respect to the primary outcome.

Severe Pulmonary hypertension secondary to a non-cardiac condition.

Uncontrolled Obstructive Sleep Apnoea secondary to a non-cardiac condition.

Severe renal impairment (e.g., estimated Glomerular Filtration Rate (eGFR) less than 30 mL/min/1.73 m²).

Advanced Liver Disease (Child-Pugh Score greater than or equal to B7 or Model for End-Stage Liver Disease (MELD) Score greater than or equal to 15).

Untreated iron deficiency defined as Serum Ferritin less than 100 ng/mL, or Serum Ferritin between 100-299 ng/mL with Transferrin Saturation (TSAT) less than 20%.

Study design

Purpose of the study

Treatment

Allocation to intervention

Non-randomised 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

Open (masking not used)

Who is / are masked / blinded?

Intervention assignment

Single group

Other design features

Phase

Not Applicable

Type of endpoint/s

Statistical methods / analysis

Recruitment

Recruitment status

Not yet recruiting

Date of first participant enrolment

Anticipated

4/08/2025

Actual

Date of last participant enrolment

Anticipated

1/07/2026

Actual

Date of last data collection

Anticipated

6/07/2027

Actual

Sample size

Target

Accrual to date

Final

Recruitment in Australia

Recruitment state(s)

QLD

Funding & Sponsors

Funding source category [1]

Hospital

Name [1]

In-Kind Support from Princess Alexandra Hospital

Address [1]

Country [1]

Australia

Primary sponsor type

Hospital

Name

Princess Alexandra Hospital

Address

Country

Australia

Secondary sponsor category [1]

None

Name [1]

Address [1]

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Gold Coast Hospital and Health Service Human Research Ethics Committee

Ethics committee address [1]

https://www.goldcoast.health.qld.gov.au/research/researchers/ethics/human-research-ethics-committee

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

29/01/2024

Approval date [1]

25/03/2025

Ethics approval number [1]

Summary

Brief summary

This study looks at patients with heart failure who have a special type of pacemaker called CRT, but sadly aren't feeling much better. Researchers want to test if upgrading this pacemaker using a newer technique, called Left Bundle Branch Area Pacing (LBBAP), is a practical option for these patients. The main goal isn't to prove the upgrade works yet, but simply to see if the procedure itself, recruiting patients, and follow-up appointments can be done smoothly at the Gold Coast University and Princess Alexandra Hospitals. About 25 patients will participate in this initial 'feasibility' study. The results will help doctors decide if it's worth doing a larger study in the future to properly check if this pacemaker upgrade helps improve patients' health and quality of life.

Trial website

Trial related presentations / publications

Public notes

Contacts

Principal investigator

Name

Dr Matthew Rowe

Address

Princess Alexandra Hospital, 199 Ipswich Rd, Woolloongabba QLD 4102

Country

Australia

Phone

+61 07 31762111

Fax

[email protected]

Contact person for public queries

Name

Dr Patrick Brown

Address

Princess Alexandra Hospital, 199 Ipswich Rd, Woolloongabba QLD 4102

Country

Australia

Phone

+61 07 31762111

Fax

[email protected]

Contact person for scientific queries

Name

Dr Patrick Brown

Address

Princess Alexandra Hospital, 199 Ipswich Rd, Woolloongabba QLD 4102

Country

Australia

Phone

+61 07 31762111

Fax

[email protected]

Data sharing statement

Will the study consider sharing individual participant data?

What supporting documents are/will be available?

Type	Citation	Link	Email	Other Details	Attachment
Ethical approval					2025.03.25 HREC Approval letter_105789.pdf
Informed consent form					PICF (UPGRADE-CRT)_MASTER COPY v4 25.03.2025_clean.docx
Study protocol					UPGRADE CRT PROTOCOL FINAL v4 25 FEB 2025_clean (comments removed).docx

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.

Trial Review

Documents added manually

Documents added automatically