Efficacy Study of Pacemakers to Treat Slow Heart Rate in... | NCT02145351

Status Module

Name	Class
Medtronic	INDUSTRY

Arms/Interventions Module

Arm Groups

Label	Type	Description	Intervention Names
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.	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	Device: Rate adaptive atrial pacing using a dual-chamber pacemaker Device: Pacemaker system will be implanted but set to Pacing Off.

Interventions

Name	Type	Description	Arm Group Labels	Other Names
Rate adaptive atrial pacing using a dual-chamber pacemaker	Device	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.

Outcomes Module

Primary Outcomes

Measure	Description	Time Frame
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.	baseline, after 4 weeks of treatment

Secondary Outcomes

Measure	Description	Time Frame
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.	4 weeks after pacemaker activation

Other Outcomes

Measure	Description	Time Frame
Mean Peak Heart Rate (HR)	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).	4 weeks

Eligibility Module

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

Name	Affiliation	Role
Barry Borlaug, MD	Mayo Clinic	Principal Investigator

Facility	Status	City	State	ZIP	Country	Contacts
Mayo Clinic in Rochester		Rochester	Minnesota	55905	United States

PubMed Identifier	Type	Citation	Retractions
36871285	Derived	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.

Label	URL
Mayo Clinic Clinical Trials	View source

Results Section

Participant Flow Module

Arm/Group Information

ID	Title	Description
FG000	Pacing Off First, Then Pacing on	Subjects who received pacing off in either the first or last 4 weeks of the study Pacing off for the first for 4 weeks, followed by 4 week washout period, and then cross-over to pacing on for an additional 4 weeks. 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. Pacemaker system implanted but set to Pacing Off.: The identical pacing system will be implanted, but will be set to Pacing Off.

Baseline Characteristics Module

Outcome Measures Module

Adverse Events Module

More Info Module

Type	Includes Protocol	Includes SAP	Includes ICF	Document Label	Document Date	Document Uploaded Date	Document File Name
Prot_SAP	Yes	Yes	No	Study Protocol and Statistical Analysis Plan	Sep 30, 2021

Arm/Group Information

ID	Title	Description
BG000	Pacing Off First, Then Pacing on	Subjects who received pacing off in either the first or last 4 weeks of the study Pacing off for the first for 4 weeks, followed by 4 week washout period, and then cross-over to pacing on for an additional 4 weeks. 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. Pacemaker system implanted but set to Pacing Off.: The identical pacing system will be implanted, but will be set to Pacing Off.
BG001	Pacing on First, Then Pacing Off	Subjects who received pacing on either the first or last 4 weeks of the study 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 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. Pacemaker system implanted but set to Pacing Off.: The identical pacing system will be implanted, but will be set to Pacing Off.
BG002	Total	Total of all reporting groups

Units	Counts
Participants	BG00015 BG00114 BG00229

Type

Title

Description

Population Description

Reporting Status

Anticipated Posting Date

Parameter Type

Dispersion Type

Unit of Measure

Calculate Percentage

Time Frame

Units Analyzed

Denominator Units Selected

Arm/Group Information

Denominators

Classes

Analyses

Primary

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.

Posted

Mean

Standard Deviation

ml/kg/min

baseline, after 4 weeks of treatment

ID	Title	Description
OG000	Pacing Off	Subjects who received pacing off in either the first or last 4 weeks of the study
OG001	Pacing on	Subjects who received pacing on either the first or last 4 weeks of the study

Units	Counts
Participants	OG00029 OG00129

Title

Denominators

Categories

Title	Measurements
	OG00010.4± 2.9 OG00110.7± 2.6

Secondary

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.

Posted

Mean

Standard Deviation

ml/kg/min

4 weeks after pacemaker activation

ID	Title	Description
OG000	Pacing Off	Subjects who received pacing off in either the first or last 4 weeks of the study
OG001	Pacing on	Subjects who received pacing on either the first or last 4 weeks of the study

Units	Counts
Participants	OG000

Secondary

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).

Posted

Mean

Standard Deviation

ratio

4 weeks

ID	Title	Description
OG000	Pacing Off	Subjects who received pacing off in either the first or last 4 weeks of the study
OG001	Pacing on	Subjects who received pacing on either the first or last 4 weeks of the study

Units	Counts
Participants	OG000

Secondary

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.

Posted

Mean

Standard Deviation

pg/mL

baseline, after 4 weeks of treatment

ID	Title	Description
OG000	Pacing Off	Subjects who received pacing off in either the first or last 4 weeks of the study
OG001	Pacing on	Subjects who received pacing on either the first or last 4 weeks of the study

Units	Counts
Participants	OG000

Secondary

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.

Posted

Mean

Standard Deviation

score on a scale

baseline, after 4 weeks of treatment

ID	Title	Description
OG000	Pacing Off	Subjects who received pacing off in either the first or last 4 weeks of the study
OG001	Pacing on	Subjects who received pacing on either the first or last 4 weeks of the study

Other Pre-specified

Mean Peak Heart Rate (HR)

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).

Posted

Mean

Standard Deviation

bpm

4 weeks

ID	Title	Description
OG000	Pacing Off	Subjects who received pacing off in either the first or last 4 weeks of the study
OG001	Pacing on	Subjects who received pacing on either the first or last 4 weeks of the study

Units	Counts
Participants	OG000

Arm/Groups

ID	Title	Description	Deaths (At Risk)	Serious Events (Affected)	Serious Events (At Risk)	Other Events (Affected)	Other Events (At Risk)
EG000	Pacing Off	Subjects who received pacing off in either the first or last 4 weeks of the study Pacemaker system implanted but set to Pacing Off.: The identical pacing system will be implanted, but will be set to Pacing Off.	29	0	29	8	29
EG001	Pacing on	Subjects who received pacing on either the first or last 4 weeks of the study 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.	29	0	29	7	29
EG002	Pacemaker Implantation	Subjects who experience adverse events during pacemaker implantation procedure only. This would be the timeframe after consent and prior to randomization to either pacing off or pacing on.	32	1	32	5	32
EG003	Washout Period	After first intervention, both pacing off and pacing on groups will have a 4 week washout period when the pacemaker is turned off.	29	0	29	0	29

Other Adverse Events

Term	Organ System	Assessment Type	Statistical Information
Chest discomfort/palpitations	Cardiac disorders	Systematic Assessment	EG0001 affected29 at risk EG0015 affected29 at risk EG0020 affected32 at risk EG0030 affected29 at risk
Pacing lead induced tricuspid regurgitation	Cardiac disorders	Systematic Assessment	EG0000 affected29 at risk EG0010 affected29 at risk EG0021 affected32 at risk EG003
Upper extremity deep venous thrombosis	Cardiac disorders	Systematic Assessment	EG0000 affected29 at risk EG0010 affected29 at risk EG0021 affected32 at risk EG003
Incision site reaction	Skin and subcutaneous tissue disorders	Systematic Assessment	EG0000 affected29 at risk EG0010 affected29 at risk EG0023 affected32 at risk EG003
Dizziness	Nervous system disorders	Systematic Assessment	EG0003 affected29 at risk EG0010 affected29 at risk EG0020 affected32 at risk EG003
Worsening fatigue	General disorders	Systematic Assessment	EG0002 affected29 at risk EG0011 affected29 at risk EG0020 affected32 at risk EG003
Non pacemaker infection	Infections and infestations	Systematic Assessment	EG0002 affected29 at risk EG0011 affected29 at risk EG0020 affected32 at risk EG003

ID	Term
D006331	Heart Diseases
D002318	Cardiovascular Diseases