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

Primary Purpose

Heart Failure With a Preserved Ejection Fraction, Heart Failure, Diastolic, Chronotropic Incompetence

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Rate adaptive atrial pacing using a dual-chamber pacemaker
Pacemaker system will be implanted but set to Pacing Off.
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Heart Failure With a Preserved Ejection Fraction focused on measuring HFpEF, Heart failure, Heart failure with preserved ejection fraction, Chronotropic incompetence

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Mayo Clinic in Rochester

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Experimental

Arm Label

Pacing off first, then pacing on

Pacing on first, then pacing off

Arm Description

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 for the first for 4 weeks, followed by 4 week washout period, and then cross-over to pacing off for an additional 4 weeks

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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).
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.
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.

Full Information

First Posted
May 20, 2014
Last Updated
March 31, 2023
Sponsor
Mayo Clinic
Collaborators
Medtronic
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1. Study Identification

Unique Protocol Identification Number
NCT02145351
Brief Title
Efficacy Study of Pacemakers to Treat Slow Heart Rate in Patients With Heart Failure
Acronym
RAPID-HF
Official Title
Rate-Adaptive Atrial Pacing In Diastolic Heart Failure (RAPID-HF)
Study Type
Interventional

2. Study Status

Record Verification Date
March 2023
Overall Recruitment Status
Completed
Study Start Date
April 7, 2014 (Actual)
Primary Completion Date
May 9, 2022 (Actual)
Study Completion Date
May 9, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Mayo Clinic
Collaborators
Medtronic

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
Yes
Data Monitoring Committee
No

5. 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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Heart Failure With a Preserved Ejection Fraction, Heart Failure, Diastolic, Chronotropic Incompetence
Keywords
HFpEF, Heart failure, Heart failure with preserved ejection fraction, Chronotropic incompetence

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
32 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Pacing off first, then pacing on
Arm Type
Active Comparator
Arm Description
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.
Arm Title
Pacing on first, then pacing off
Arm Type
Experimental
Arm Description
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
Intervention Type
Device
Intervention Name(s)
Rate adaptive atrial pacing using a dual-chamber pacemaker
Other Intervention Name(s)
Medtronic Azure XT DR MRI pacemaker model W1DR01, Medtronic CapSureFix MRI model 5086
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Pacemaker system will be implanted but set to Pacing Off.
Other Intervention Name(s)
Medtronic Azure XT DR MRI model W1DR01, Medtronic CapSureFix MRI model 5086
Intervention Description
The identical pacing system will be implanted, but will be set to Pacing Off.
Primary Outcome Measure Information:
Title
Change in Oxygen Consumption (VO2) at Ventilatory Anaerobic Threshold (VAT)
Description
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.
Time Frame
baseline, after 4 weeks of treatment
Secondary Outcome Measure Information:
Title
Peak Aerobic Capacity (Peak VO2)
Description
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.
Time Frame
4 weeks after pacemaker activation
Title
Ventilatory Efficiency (VE/VCO2)
Description
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).
Time Frame
4 weeks
Title
Change in Plasma N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)
Description
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.
Time Frame
baseline, after 4 weeks of treatment
Title
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score
Description
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.
Time Frame
baseline, after 4 weeks of treatment
Other Pre-specified Outcome Measures:
Title
Mean Peak Heart Rate (HR)
Description
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).
Time Frame
4 weeks

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria 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. Exclusion Criteria 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) 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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Barry Borlaug, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic in Rochester
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Plan to Share IPD
No
Links:
URL
https://www.mayo.edu/research/clinical-trials
Description
Mayo Clinic Clinical Trials

Learn more about this trial

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

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