Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12623001187639
Ethics application status
Approved
Date submitted
19/10/2023
Date registered
17/11/2023
Date last updated
3/04/2024
Date data sharing statement initially provided
17/11/2023
Type of registration
Prospectively registered

Titles & IDs
Public title
Effect of Accelerated Pacing Rates on Exercise Tolerance, Quality of Life and Arrhythmia Burden in Patients with Evidence of Heart Failure with Preserved Ejection Fraction
Scientific title
Effect of Accelerated Pacing Rates on Exercise Tolerance, Quality of Life and Arrhythmia Burden in Patients with Evidence of Heart Failure with Preserved Ejection Fraction: The PACE-UP Randomised Controlled Trial
Secondary ID [1] 310710 0
None
Universal Trial Number (UTN)
Trial acronym
PACE-UP
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Heart failure with preserved ejection fraction 331643 0
Sinus Node Disease 331732 0
Condition category
Condition code
Cardiovascular 328363 328363 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants randomised to the intervention arm will have their permanent pacemaker device adjusted to a lower rate setting of 75bpm, and followed up with assessments at 4-weeks and 52-weeks post-randomisation. Adjustment of the lower rate setting will be performed by a cardiac physiologist during the baseline pacemaker interrogation at the Cardiovascular Centre, Norwood. The baseline pacemaker interrogation involves the participant remaining seated, while the cardiac physiologist places a wand over the participants chest where the device is located. This allows the pacemaker settings and performance to visualised by the cardiac physiologist on a pacemaker compatible computer. The pacemaker interrogation will be 15-minutes in duration, and include the adjustment of the lower rate settings. The cardiac physiologist modifying pacemaker settings and the supervising cardiologist will not be involved in assessment of any study outcomes.
Intervention code [1] 327132 0
Treatment: Devices
Comparator / control treatment
Participants randomised to the usual care arm will be maintained at the standard 60bpm setting. To facilitate participant blinding, participants in the usual care arm will still undergo a baseline pacemaker interrogation.
Control group
Active

Outcomes
Primary outcome [1] 336231 0
Peak oxygen consumption (VO2peak).
Timepoint [1] 336231 0
Baseline and 52-weeks post-randomisation.
Secondary outcome [1] 427458 0
Composite of physical symptoms, functional limitations, and psychosocial effects.
Timepoint [1] 427458 0
Baseline, 4-weeks and 52-weeks post-randomisation.
Secondary outcome [2] 427459 0
Cognitive function
Timepoint [2] 427459 0
Baseline, 4-weeks and 52-weeks post-randomisation.
Secondary outcome [3] 427464 0
N-terminal Pro-Brain Natriuretic Peptide (NT-ProBNP).
Timepoint [3] 427464 0
Baseline and 52-weeks post-randomisation.
Secondary outcome [4] 427465 0
Device-detected arrhythmia burden.
Timepoint [4] 427465 0
52-weeks post-randomisation.
Secondary outcome [5] 427466 0
Device-detected physical activity.
Timepoint [5] 427466 0
52-weeks post-randomisation.
Secondary outcome [6] 428037 0
Resting transthoracic echocardiography, left atrial volume indexed to body surface area.
Timepoint [6] 428037 0
Baseline, 4-weeks and 52-weeks post-randomisation.
Secondary outcome [7] 428039 0
Resting transthoracic echocardiography, left ventricle volume.
Timepoint [7] 428039 0
Baseline, 4-weeks and 52-weeks post-randomisation.
Secondary outcome [8] 428040 0
Resting transthoracic echocardiography, left ventricular volume.
Timepoint [8] 428040 0
Baseline, 4-weeks and 52-weeks post-randomisation.
Secondary outcome [9] 428041 0
Resting transthoracic echocardiography, left atrial function.
Timepoint [9] 428041 0
Baseline, 4-weeks and 52-weeks post-randomisation.
Secondary outcome [10] 428042 0
Resting transthoracic echocardiography, left ventricular function.
Timepoint [10] 428042 0
Baseline, 4-weeks and 52-weeks post-randomisation.
Secondary outcome [11] 428043 0
Exercise transthoracic echocardiography, left atrial volume indexed to body surface area.
Timepoint [11] 428043 0
Baseline, 4-weeks and 52-weeks post-randomisation.
Secondary outcome [12] 428044 0
Exercise transthoracic echocardiography, left ventricle volume.
Timepoint [12] 428044 0
Baseline, 4-weeks and 52-weeks post-randomisation.
Secondary outcome [13] 428045 0
Exercise transthoracic echocardiography, left ventricular volume.
Timepoint [13] 428045 0
Baseline, 4-weeks and 52-weeks post-randomisation.
Secondary outcome [14] 428046 0
Exercise transthoracic echocardiography, left atrial function.
Timepoint [14] 428046 0
Baseline, 4-weeks and 52-weeks post-randomisation.
Secondary outcome [15] 428047 0
Exercise transthoracic echocardiography, left ventricular function.
Timepoint [15] 428047 0
Baseline, 4-weeks and 52-weeks post-randomisation.

Eligibility
Key inclusion criteria
• Adults 18-80 years old with a pacemaker.
• Preclinical or clinical heart failure with preserved ejection fraction according to the diagnostic criteria of the HFA of the ESC.
• Sinus node dysfunction with intact AV node conduction or minimal RV pacing (<20%) and paced QRS <150ms.

OR

• Impaired AV node conduction with His bundle or left bundle branch area pacing, or biventricular pacing.
• Subject is expected to remain available for follow-up visits.
Minimum age
18 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• Left ventricular ejection fraction <45%.
• Inability to participate in exercise testing due to musculoskeletal disease or other active diseases.
• Myocardial infarction within the past 12 months.
• Infiltrative cardiomyopathy.
• Hypertrophic cardiomyopathy.
• More than moderate valvular stenosis or regurgitation.
• Aortic valve replacement in the past one year.
• Significant primary pulmonary disease on home oxygen.
• Uncontrolled hypertension as defined by BP >160/100 mmHg on two measurements >15 minutes apart.

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)
Research personnel involved in the collection of primary and secondary endpoints will be concealed to the group allocation. Group allocation will be performed by a clinical trials coordinator.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Participants will be randomised 1:1 using a computer-generated web-based randomisation schedule.
Masking / blinding
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
Recruiting
Date of first participant enrolment
Anticipated
6/03/2024
Actual
6/03/2024
Date of last participant enrolment
Anticipated
23/02/2025
Actual
Date of last data collection
Anticipated
23/02/2025
Actual
Sample size
Target
160
Accrual to date
1
Final
Recruitment in Australia
Recruitment state(s)
SA

Funding & Sponsors
Funding source category [1] 314925 0
University
Name [1] 314925 0
University of Adelaide
Country [1] 314925 0
Australia
Funding source category [2] 315066 0
Charities/Societies/Foundations
Name [2] 315066 0
Heart Foundation
Country [2] 315066 0
Australia
Primary sponsor type
University
Name
University of Adelaide
Address
North Terrace, Adelaide, South Australia 5005
Country
Australia
Secondary sponsor category [1] 316930 0
None
Name [1] 316930 0
Address [1] 316930 0
Country [1] 316930 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313916 0
Central Adelaide Local Health Network Human Research Ethics Committee
Ethics committee address [1] 313916 0
Port Road, Adelaide, SA, 5000
Ethics committee country [1] 313916 0
Australia
Date submitted for ethics approval [1] 313916 0
25/09/2023
Approval date [1] 313916 0
07/02/2024
Ethics approval number [1] 313916 0
2023/HRE00321

Summary
Brief summary
Heart failure with preserved ejection fraction (HFpEF) is the most prevalent phenotype of heart failure. However, the treatment options for these patients remain limited. Permanent pacemakers are commonly used in the management of bradycardia (low heart rate), with many pacemaker patients also presenting with early HFpEF. This study is a prospective, two-arm randomised controlled trial including 160 participants with pacemakers and early HFpEF from Adelaide, South Australia. Participants will be randomised to an accelerated pacing rate (75bpm) or usual care (60bpm), performing follow-up at 4-weeks and 52-weeks post randomisation. It is hypothesised that increasing the heart rate settings compared to standard permanent pacemaker settings, will improve exercise tolerance, defined using peak oxygen consumption, at 12-months post-randomisation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 129782 0
Dr Adrian Elliott
Address 129782 0
South Australian Health and Medical Research Institute - North Terrace, Adelaide, SA, 5000
Country 129782 0
Australia
Phone 129782 0
+61 8 8128 4648
Fax 129782 0
Email 129782 0
adrian.elliott@adelaide.edu.au
Contact person for public queries
Name 129783 0
Mr Jackson Howie
Address 129783 0
South Australian Health and Medical Research Institute - North Terrace, Adelaide, SA, 5000
Country 129783 0
Australia
Phone 129783 0
+61 8 8128 4591
Fax 129783 0
Email 129783 0
jackson.howie@adelaide.edu.au
Contact person for scientific queries
Name 129784 0
Dr Adrian Elliott
Address 129784 0
South Australian Health and Medical Research Institute - North Terrace, Adelaide, SA, 5000
Country 129784 0
Australia
Phone 129784 0
+61 8 8128 4648
Fax 129784 0
Email 129784 0
adrian.elliott@adelaide.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


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.