Heart Failure With a Preserved Ejection FractionRAPID-HFNCT02145351

Efficacy Study of Pacemakers to Treat Slow Heart Rate in Patients With Heart Failure

A study testing Rate adaptive atrial pacing using a dual-chamber pacemaker and Pacemaker system will be implanted but set to Pacing Off. in people with Heart Failure With a Preserved Ejection Fraction and Heart Failure, Diastolic, run by Mayo Clinic at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

Determine the impact of restoring normal heart rate response during exercise and daily activity in patients with heart failure and a preserved ejection fraction (HFpEF) and chronotropic incompetence (CI). Read more about this study

Who is it for?: Ages 18 years and older
Conditions the study is for: Heart Failure With a Preserved Ejection Fraction, Heart Failure, Diastolic, Chronotropic Incompetence
What is being tested?: Rate adaptive atrial pacing using a dual-chamber pacemaker and Pacemaker system will be implanted but set to Pacing Off.
Type of treatment: Medical device
Could I receive a placebo?: No, everyone receives an active treatment
How many people: 32 participants
Where: 1 siteUnited States
Study dates: 7 Apr 2014to 9 May 2022
Phase: Interventional
Are there results?: Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 years and older
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Age >18 years and able to provide informed consent to enroll in the trial, or consent through a legal guardian or power of attorney.
Previous clinical diagnosis of HF with current NYHA Class II-III symptoms
At least one of the following: Hospitalization for decompensated HF, Acute treatment for HF with intravenous loop diuretic or hemofiltration, Chronic treatment with a loop diuretic for control of HF symptoms + left atrial enlargement on echocardiography or E/e' ratio (≥14 average, ≥15 septal ) on echocardiography, Resting PCWP >15 mm Hg or LV end-diastolic pressure >18 mmHg at catheterization for dyspnea and/or exercise PCWP/LV end-diastolic pressure >25 mmHg, or Elevated NT-proBNP level (≥300 pg/ml )
Left ventricular EF ≥40% within 12 months with clinical stability
Stable cardiac medical therapy for ≥30 days
Sinus rhythm
Chronotropic incompetence on recent (within 6 months) clinical or screening exercise test, defined as heart rate reserve (HRR) <0.80 or <0.62 if on beta blockers
Meet both screening criteria on clinically-performed cardiopulmonary exercise testing within 12 months.

Who cannot join

Inability to exercise, or non-cardiac condition that precludes exercise testing
Any contraindication to a pacemaker system
Non-cardiac condition limiting life expectancy to less than one year
Significant left sided structural valve disease (>mild stenosis, >moderate regurgitation)
Hypertrophic cardiomyopathy
Infiltrative or inflammatory myocardial disease (amyloid, sarcoid)

Show all 22Show fewer

Pericardial disease
Non-group 2 pulmonary arterial hypertension
Chronic stable exertional angina
Acute coronary syndrome or revascularization within 60 days
Other clinically important causes of dyspnea
Atrial fibrillation
PR interval >210 msec
Resting heart rate (HR) > 100 bpm
A history of reduced ejection fraction (EF<40%)
Advanced chronic kidney disease (GFR < 20 ml/min/1.73m2 by modified MDRD equation)
Women of child bearing potential without negative pregnancy test and effective contraception
Severe anemia (Hemoglobin <10 g/dL)
Severe hepatic disease
Complex congenital heart disease
Listed for cardiac transplantation
Other class I indications for pacing

Trial locations and contacts

1 site in 1 country.

United States1 site

Mayo Clinic in Rochester
Rochester, Minnesota, 55905

Other trials in United States

About this study

Official title: Rate-Adaptive Atrial Pacing In Diastolic Heart Failure (RAPID-HF)

Conditions: Heart Failure With a Preserved Ejection Fraction, Heart Failure, Diastolic, Chronotropic Incompetence
Being tested: Rate adaptive atrial pacing using a dual-chamber pacemaker, Pacemaker system will be implanted but set to Pacing Off.
Keywords: HFpEF, Heart failure, Heart failure with preserved ejection fraction, Chronotropic incompetence
Medical subject headings: Heart Failure, Diastolic, Heart Failure

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Rate adaptive atrial pacing using a dual-chamber pacemakerDevice
Also called Medtronic Azure XT DR MRI pacemaker model W1DR01, Medtronic CapSureFix MRI model 5086
The Azure XT DR is a permanent, dual-chamber cardiac pacemaker with the ability to continuously monitor and record patient activity, and respond to activity by pacing faster and increasing the heart rate (rate adaptive atrial pacing). It will be programmed in AAIR mode to pace the right atrium. The leads will be placed in the right atrium and right ventricle using CapSureFix model 5086.
Pacemaker system will be implanted but set to Pacing Off.Device
Also called Medtronic Azure XT DR MRI model W1DR01, Medtronic CapSureFix MRI model 5086
The identical pacing system will be implanted, but will be set to Pacing Off.

Study groups in NCT02145351
Study group	Role	What they receive
Pacing off first, then pacing on	Active comparator	No-pacing on for the first for 4 weeks, followed by 4 week washout period, and then cross-over to pacing on for an additional 4 weeks. Receives: Device: Rate adaptive atrial pacing using a dual-chamber pacemaker; Device: Pacemaker system will be implanted but set to Pacing Off.
Pacing on first, then pacing off	Experimental	Pacing on for the first for 4 weeks, followed by 4 week washout period, and then cross-over to pacing off for an additional 4 weeks Receives: Device: Rate adaptive atrial pacing using a dual-chamber pacemaker; Device: Pacemaker system will be implanted but set to Pacing Off.

What is being measured

The primary outcome is the main question the study is designed to answer.

Change in Oxygen Consumption (VO2) at Ventilatory Anaerobic Threshold (VAT)
Maximal effort cardiopulmonary exercise testing was performed on a treadmill after 4 weeks of pacing-on and after 4 weeks of pacing-off to measure volumes of oxygen consumed (VO2). Change in VO2 at anaerobic threshold (VO2,AT) determined by the V-Slope method as the point of disproportionate rise in VCO2 relative to VO2 as measured in ml/kg/min.
Measured: baseline, after 4 weeks of treatment

Secondary outcomes (4)

Peak Aerobic Capacity (Peak VO2)
Determined as the mean of values obtained over the final 30 seconds of exercise. Maximal effort cardiopulmonary exercise testing was performed on a treadmill after 4 weeks of pacing-on and after 4 weeks of pacing-off to measure volumes of oxygen consumed (VO2). As measured in ml/kg/min.
Measured: 4 weeks after pacemaker activation
Ventilatory Efficiency (VE/VCO2)
Determined as the nadir of VE/VCO2 ratio during exercise. Maximal effort cardiopulmonary exercise testing was performed on a treadmill after 4 weeks of pacing-on and after 4 weeks of pacing-off to measure volumes of oxygen consumed (VO2).
Measured: 4 weeks
Change in Plasma N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)
Change in plasma NT-proBNP as measured in pg/mL. Natriuretic peptides are substances made by the heart. A main type of these substances is NT-proBNP. Elevated levels can mean the heart isn't pumping as much blood the body needs.
Measured: baseline, after 4 weeks of treatment
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score
Change from baseline in KCCQ-overall summary score was reported. KCCQ was a 23-item, self-administered questionnaire that measure the participant's perception of their health status, including their heart failure (HF) symptoms, impact on physical and social function and how their HF impacts the quality of life. KCCQ quantifies 7 domains: physical limitations (6 items), symptom stability (1 item), symptom frequency (4 items), symptom burden (3 items), self-efficacy (2 items), quality of life (3 items) and social limitations (4 items). Scores were generated for each domain and scaled from 0 to 100, with 0 denoting the worst and 100 the best possible status. KCCQ- overall summary score was average of domains- physical limitation, total symptoms (average of symptom frequency and symptom burden), quality of life, and social limitation, and transformed to a single score which ranged from 0 (worst) -100 (the best possible status), where the higher score reflected better health status.
Measured: baseline, after 4 weeks of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

7 Apr 20149 May 2022

First posted22 May 2014 (estimated)
Study start7 Apr 2014
Primary completion9 May 2022
Study completion9 May 2022

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (1)Papers the sponsor has linked to this study.
Other trials for Heart Failure With a Preserved Ejection FractionStudies of the same condition, open and under way.
More trials run by Mayo ClinicThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase N/A
Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 32 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02145351
Sponsor's protocol ID: 13-008306
Acronym: RAPID-HF
Status last verified: Mar 2023
First submitted: 20 May 2014
Last updated: 5 Apr 2023
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: No
FDA-regulated drug: No
FDA-regulated device: Yes
Individual data sharing: No

Publications

Reddy YNV, Koepp KE, Carter R, Win S, Jain CC, Olson TP, Johnson BD, Rea R, Redfield MM, Borlaug BA. Rate-Adaptive Atrial Pacing for Heart Failure With Preserved Ejection Fraction: The RAPID-HF Randomized Clinical Trial. JAMA. 2023 Mar 14;329(10):801-809. doi: 10.1001/jama.2023.0675.
PubMed 36871285

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life
Heart Failure With Preserved Ejection Fraction, Iron Deficiencies
RecruitingObservational study
Descriptive Study of Circulating Gene or Protein Inflammatory Biomarkers and Bioimpedance Parameters in a Population of Patients Hospitalized for Decompensated Heart Failure With Preserved or Mildly Reduced Cardiac Function
Inflammation Biomarkers, Heart Failure
Recruiting
Remote Rehabilitation in Patients With HFpEF (PATRON-HF)
Heart Failure With Preserved Ejection Fraction
RecruitingPhase 2
The Clinical Trial of Tamibarotene for Patients With HFpEF (RELIEF Trial)
HFpEF - Heart Failure With Preserved Ejection Fraction

All Heart Failure With a Preserved Ejection Fraction trials

Study at a glance

From the registry record, last updated by the sponsor on 5 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: Rate-Adaptive Atrial Pacing In Diastolic Heart Failure (RAPID-HF)
ClinicalTrials.gov ID: NCT02145351
Acronym / sponsor ID: RAPID-HF / 13-008306
Conditions: Heart Failure With a Preserved Ejection Fraction, Heart Failure, Diastolic, Chronotropic Incompetence
Keywords: HFpEF, Heart failure, Heart failure with preserved ejection fraction, Chronotropic incompetence
Study type: Interventional
Recruitment status: Completed
Enrolment: 32 participants (actual)
Lead sponsor: Mayo ClinicUniversity, hospital or other
Collaborators: Medtronic
Study start: 7 Apr 2014 (actual)
Primary completion: 9 May 2022 (actual)
Study completion: 9 May 2022 (actual)
First posted: 22 May 2014 (estimated)
Results: Posted 5 Apr 2023

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Treatment
Allocation: Randomised
Intervention model: Crossover
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Pacing off first, then pacing on	Active comparator	Device: Rate adaptive atrial pacing using a dual-chamber pacemaker, Device: Pacemaker system will be implanted but set to Pacing Off.No-pacing on for the first for 4 weeks, followed by 4 week washout period, and then cross-over to pacing on for an additional 4 weeks.
Pacing on first, then pacing off	Experimental	Device: Rate adaptive atrial pacing using a dual-chamber pacemaker, Device: Pacemaker system will be implanted but set to Pacing Off.Pacing on for the first for 4 weeks, followed by 4 week washout period, and then cross-over to pacing off for an additional 4 weeks

Who may qualify

Ages: 18 years and older
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (8 listed)

Age >18 years and able to provide informed consent to enroll in the trial, or consent through a legal guardian or power of attorney.
Previous clinical diagnosis of HF with current NYHA Class II-III symptoms
At least one of the following: Hospitalization for decompensated HF, Acute treatment for HF with intravenous loop diuretic or hemofiltration, Chronic treatment with a loop diuretic for control of HF symptoms + left atrial enlargement on echocardiography or E/e' ratio (≥14 average, ≥15 septal ) on echocardiography, Resting PCWP >15 mm Hg or LV end-diastolic pressure >18 mmHg at catheterization for dyspnea and/or exercise PCWP/LV end-diastolic pressure >25 mmHg, or Elevated NT-proBNP level (≥300 pg/ml )
Left ventricular EF ≥40% within 12 months with clinical stability
Stable cardiac medical therapy for ≥30 days

Key exclusion criteria (22 listed)

Inability to exercise, or non-cardiac condition that precludes exercise testing
Any contraindication to a pacemaker system
Non-cardiac condition limiting life expectancy to less than one year
Significant left sided structural valve disease (>mild stenosis, >moderate regurgitation)
Hypertrophic cardiomyopathy

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
Rate adaptive atrial pacing using a dual-chamber pacemakerAlso: Medtronic Azure XT DR MRI pacemaker model W1DR01, Medtronic CapSureFix MRI model 5086The Azure XT DR is a permanent, dual-chamber cardiac pacemaker with the ability to continuously monitor and record patient activity, and respond to activity by pacing faster and increasing the heart rate (rate adaptive atrial pacing). It will be programmed in AAIR mode to pace the right atrium. The leads will be placed in the right atrium and right ventricle using CapSureFix model 5086.	Device	Pacing off first, then pacing on, Pacing on first, then pacing off
Pacemaker system will be implanted but set to Pacing Off.Also: Medtronic Azure XT DR MRI model W1DR01, Medtronic CapSureFix MRI model 5086The identical pacing system will be implanted, but will be set to Pacing Off.	Device	Pacing off first, then pacing on, Pacing on first, then pacing off

Primary outcome

Change in Oxygen Consumption (VO2) at Ventilatory Anaerobic Threshold (VAT)
Time frame: baseline, after 4 weeks of treatment
Maximal effort cardiopulmonary exercise testing was performed on a treadmill after 4 weeks of pacing-on and after 4 weeks of pacing-off to measure volumes of oxygen consumed (VO2). Change in VO2 at anaerobic threshold (VO2,AT) determined by the V-Slope method as the point of disproportionate rise in VCO2 relative to VO2 as measured in ml/kg/min.

4 secondary outcomes

Peak Aerobic Capacity (Peak VO2)
Time frame: 4 weeks after pacemaker activation
Ventilatory Efficiency (VE/VCO2)
Time frame: 4 weeks
Change in Plasma N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)
Time frame: baseline, after 4 weeks of treatment
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score
Time frame: baseline, after 4 weeks of treatment

Results and safety

Results posted to the registry on 5 Apr 2023, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Pacing Off First, Then Pacing on	0	0
Pacing on First, Then Pacing Off	0	0
Pacemaker Implantation	32	32

Primary outcome: Change in Oxygen Consumption (VO2) at Ventilatory Anaerobic Threshold (VAT)

Time frame: baseline, after 4 weeks of treatment. Mean (Standard Deviation). Unit: ml/kg/min

Measure	Pacing Off n = 29	Pacing on n = 29
Value	10.4 (2.9)	10.7 (2.6)

4 secondary outcomes are reported in the full results.

Adverse events

Time frame: Adverse Events were assessed for all subjects during Pacemaker implantation (4 weeks), first treatment period (4 weeks), washout period (4 weeks), and second treatment period (4 weeks) for a total of approximately 16 weeks.. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Pacing Off	0 of 29 (0%)	8 of 29 (27.6%)	0 of 29
Pacing on	0 of 29 (0%)	7 of 29 (24.1%)	0 of 29
Pacemaker Implantation	1 of 32 (3.1%)	5 of 32 (15.6%)	0 of 32
Washout Period	0 of 29 (0%)	0 of 29 (0%)	0 of 29

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 5 Apr 2023.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 36871285Reddy YNV, Koepp KE, Carter R, Win S, Jain CC, Olson TP, Johnson BD, Rea R, Redfield MM, Borlaug BA. Rate-Adaptive Atrial Pacing for Heart Failure With Preserved Ejection Fraction: The RAPID-HF Randomized Clinical Trial. JAMA. 2023 Mar 14;329(10):801-809. doi: 10.1001/jama.2023.0675.
Mayo Clinic Clinical TrialsLink provided by the sponsor.
Individual participant dataSharing planned: No

Related trials for Heart Failure With a Preserved Ejection Fraction

Not yet recruitingPhase 2
A Study of Bimagrumab in Participants With HFpEF
Heart Failure, Diastolic, Diastolic Heart Failure
RecruitingPhase 4
The Effects of Ferric Derisomaltose in Patients With Acute Heart Failure and Iron Deficiency on Exercise Capacity and Quality of Life
Heart Failure With Preserved Ejection Fraction, Iron Deficiencies
RecruitingObservational study
Descriptive Study of Circulating Gene or Protein Inflammatory Biomarkers and Bioimpedance Parameters in a Population of Patients Hospitalized for Decompensated Heart Failure With Preserved or Mildly Reduced Cardiac Function
Inflammation Biomarkers, Heart Failure
Recruiting
Remote Rehabilitation in Patients With HFpEF (PATRON-HF)
Heart Failure With Preserved Ejection Fraction
RecruitingPhase 2
The Clinical Trial of Tamibarotene for Patients With HFpEF (RELIEF Trial)
HFpEF - Heart Failure With Preserved Ejection Fraction

Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Barry Borlaug, MD principal investigator

Mayo Clinic

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 5 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

Yes. Results are posted in the registry (first posted 5 Apr 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Change in Oxygen Consumption (VO2) at Ventilatory Anaerobic Threshold (VAT) (time frame: baseline, after 4 weeks of treatment). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02145351, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 5 Apr 2023.