Efficacy Study of Pacemakers to Treat Slow Heart Rate in Patients With Heart Failure (RAPID-HF)

• ClinicalTrials.gov Identifier: NCT02145351
• Recruitment Status: Completed
• First Posted: May 22, 2014
• Results First Posted: April 5, 2023
• Last Update Posted: April 5, 2023
• Sponsor: Mayo Clinic
• Collaborator: Medtronic
• Information provided by (Responsible Party): Barry Borlaug, Mayo Clinic

Study Description

Brief 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).

Condition or disease	Intervention/treatment	Phase
Heart Failure With a Preserved Ejection Fraction; Heart Failure, Diastolic; Chronotropic Incompetence	Device: Rate adaptive atrial pacing using a dual-chamber pacemaker; Device: Pacemaker system will be implanted but set to Pacing Off.	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 32 participants
• Allocation: Randomized
• Intervention Model: Crossover Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Rate-Adaptive Atrial Pacing In Diastolic Heart Failure (RAPID-HF)
• Actual Study Start Date: April 7, 2014
• Actual Primary Completion Date: May 9, 2022
• Actual Study Completion Date: May 9, 2022

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: Pacing off first, then pacing on; 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.	Device: Rate adaptive atrial pacing using a dual-chamber pacemaker; 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.; Other Names: Medtronic Azure XT DR MRI pacemaker model W1DR01; Medtronic CapSureFix MRI model 5086; Device: Pacemaker system will be implanted but set to Pacing Off.; The identical pacing system will be implanted, but will be set to Pacing Off.; Other Names: Medtronic Azure XT DR MRI model W1DR01; Medtronic CapSureFix MRI model 5086
Experimental: Pacing on first, then 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	Device: Rate adaptive atrial pacing using a dual-chamber pacemaker; 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.; Other Names: Medtronic Azure XT DR MRI pacemaker model W1DR01; Medtronic CapSureFix MRI model 5086; Device: Pacemaker system will be implanted but set to Pacing Off.; The identical pacing system will be implanted, but will be set to Pacing Off.; Other Names: Medtronic Azure XT DR MRI model W1DR01; Medtronic CapSureFix MRI model 5086

Outcome Measures

Primary Outcome Measures :

1. 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.

Secondary Outcome Measures :

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

Other Outcome Measures:

1. Mean Peak Heart Rate (HR) [ Time Frame: 4 weeks ]
   Determined as the maximum heart rate . Heart rate (or pulse rate) is the frequency of the heartbeat measured by the number of contractions of the heart per minute (beats per minute, or bpm).

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria

1. Age >18 years and able to provide informed consent to enroll in the trial, or consent through a legal guardian or power of attorney.
2. Previous clinical diagnosis of HF with current NYHA Class II-III symptoms
3. 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 )
4. Left ventricular EF ≥40% within 12 months with clinical stability
5. Stable cardiac medical therapy for ≥30 days
6. Sinus rhythm
7. 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
8. Meet both screening criteria on clinically-performed cardiopulmonary exercise testing within 12 months.

Exclusion Criteria

1. Inability to exercise, or non-cardiac condition that precludes exercise testing
2. Any contraindication to a pacemaker system
3. Non-cardiac condition limiting life expectancy to less than one year
4. Significant left sided structural valve disease (>mild stenosis, >moderate regurgitation)
5. Hypertrophic cardiomyopathy
6. Infiltrative or inflammatory myocardial disease (amyloid, sarcoid)
7. Pericardial disease
8. Non-group 2 pulmonary arterial hypertension
9. Chronic stable exertional angina
10. Acute coronary syndrome or revascularization within 60 days
11. Other clinically important causes of dyspnea
12. Atrial fibrillation
13. PR interval >210 msec
14. Resting heart rate (HR) > 100 bpm
15. A history of reduced ejection fraction (EF<40%)
16. Advanced chronic kidney disease (GFR < 20 ml/min/1.73m2 by modified MDRD equation)
17. Women of child bearing potential without negative pregnancy test and effective contraception
18. Severe anemia (Hemoglobin <10 g/dL)
19. Severe hepatic disease
20. Complex congenital heart disease
21. Listed for cardiac transplantation
22. Other class I indications for pacing

Contacts and Locations

Locations

United States, Minnesota

Mayo Clinic in Rochester

Rochester, Minnesota, United States, 55905

Sponsors and Collaborators

Mayo Clinic

Medtronic

Investigators

• Principal Investigator: Barry Borlaug, MD; Mayo Clinic

  Study Documents (Full-Text)

Documents provided by Barry Borlaug, Mayo Clinic:

Study Protocol and Statistical Analysis Plan  [PDF] September 30, 2021

More Information

Additional Information:

Mayo Clinic Clinical Trials 

• Responsible Party: Barry Borlaug, Principal Investigator, Mayo Clinic
• ClinicalTrials.gov Identifier: NCT02145351
• Other Study ID Numbers: 13-008306
• First Posted: May 22, 2014
• Results First Posted: April 5, 2023
• Last Update Posted: April 5, 2023
• Last Verified: March 2023

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: Yes

Keywords provided by Barry Borlaug, Mayo Clinic:

HFpEF; Heart failure; Heart failure with preserved ejection fraction; Chronotropic incompetence

Additional relevant MeSH terms:

Heart Failure; Heart Failure, Diastolic; Heart Diseases; Cardiovascular Diseases