Trial Outcomes & Findings for Efficacy Study of Pacemakers to Treat Slow Heart Rate in Patients With Heart Failure (NCT NCT02145351)
NCT ID: NCT02145351
Last Updated: 2023-04-05
Results Overview
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.
Recruitment status
COMPLETED
Study phase
NA
Target enrollment
32 participants
Primary outcome timeframe
baseline, after 4 weeks of treatment
Results posted on
2023-04-05
Participant Flow
Three subjects did not return for baseline testing following pacemaker implantation, leaving a total of 29 patients who were randomized into the study.
Participant milestones
| Measure |
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.
|
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.
|
Pacemaker Implantation
All subjects who had a pacemaker implanted 4 weeks prior to randomization
|
|---|---|---|---|
|
Pacemaker Implantation (4 Weeks)
STARTED
|
0
|
0
|
32
|
|
Pacemaker Implantation (4 Weeks)
COMPLETED
|
0
|
0
|
32
|
|
Pacemaker Implantation (4 Weeks)
NOT COMPLETED
|
0
|
0
|
0
|
|
First Intervention (4 Weeks)
STARTED
|
15
|
14
|
0
|
|
First Intervention (4 Weeks)
COMPLETED
|
15
|
14
|
0
|
|
First Intervention (4 Weeks)
NOT COMPLETED
|
0
|
0
|
0
|
|
Washout (4 Weeks)
STARTED
|
15
|
14
|
0
|
|
Washout (4 Weeks)
COMPLETED
|
15
|
14
|
0
|
|
Washout (4 Weeks)
NOT COMPLETED
|
0
|
0
|
0
|
|
Second Intervention (4 Weeks)
STARTED
|
15
|
14
|
0
|
|
Second Intervention (4 Weeks)
COMPLETED
|
15
|
14
|
0
|
|
Second Intervention (4 Weeks)
NOT COMPLETED
|
0
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Efficacy Study of Pacemakers to Treat Slow Heart Rate in Patients With Heart Failure
Baseline characteristics by cohort
| Measure |
Pacing Off First, Then Pacing on
n=15 Participants
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.
|
Pacing on First, Then Pacing Off
n=14 Participants
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.
|
Total
n=29 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
66.5 years
STANDARD_DEVIATION 12.2 • n=99 Participants
|
65.4 years
STANDARD_DEVIATION 6.4 • n=107 Participants
|
66.0 years
STANDARD_DEVIATION 9.7 • n=206 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=99 Participants
|
5 Participants
n=107 Participants
|
13 Participants
n=206 Participants
|
|
Sex: Female, Male
Male
|
7 Participants
n=99 Participants
|
9 Participants
n=107 Participants
|
16 Participants
n=206 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
White
|
15 Participants
n=99 Participants
|
14 Participants
n=107 Participants
|
29 Participants
n=206 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=99 Participants
|
0 Participants
n=107 Participants
|
0 Participants
n=206 Participants
|
|
Region of Enrollment
United States
|
15 participants
n=99 Participants
|
14 participants
n=107 Participants
|
29 participants
n=206 Participants
|
PRIMARY outcome
Timeframe: baseline, after 4 weeks of treatmentMaximal 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.
Outcome measures
| Measure |
Pacing Off
n=29 Participants
Subjects who received pacing off in either the first or last 4 weeks of the study
|
Pacing on
n=29 Participants
Subjects who received pacing on either the first or last 4 weeks of the study
|
|---|---|---|
|
Change in Oxygen Consumption (VO2) at Ventilatory Anaerobic Threshold (VAT)
|
10.4 ml/kg/min
Standard Deviation 2.9
|
10.7 ml/kg/min
Standard Deviation 2.6
|
SECONDARY outcome
Timeframe: 4 weeks after pacemaker activationDetermined 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.
Outcome measures
| Measure |
Pacing Off
n=29 Participants
Subjects who received pacing off in either the first or last 4 weeks of the study
|
Pacing on
n=29 Participants
Subjects who received pacing on either the first or last 4 weeks of the study
|
|---|---|---|
|
Peak Aerobic Capacity (Peak VO2)
|
16.5 ml/kg/min
Standard Deviation 4.3
|
16.8 ml/kg/min
Standard Deviation 4.1
|
SECONDARY outcome
Timeframe: 4 weeksDetermined 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).
Outcome measures
| Measure |
Pacing Off
n=29 Participants
Subjects who received pacing off in either the first or last 4 weeks of the study
|
Pacing on
n=29 Participants
Subjects who received pacing on either the first or last 4 weeks of the study
|
|---|---|---|
|
Ventilatory Efficiency (VE/VCO2)
|
34.2 ratio
Standard Deviation 6.6
|
34.9 ratio
Standard Deviation 6.3
|
SECONDARY outcome
Timeframe: baseline, after 4 weeks of treatmentChange 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.
Outcome measures
| Measure |
Pacing Off
n=29 Participants
Subjects who received pacing off in either the first or last 4 weeks of the study
|
Pacing on
n=29 Participants
Subjects who received pacing on either the first or last 4 weeks of the study
|
|---|---|---|
|
Change in Plasma N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)
|
-88.0 pg/mL
Standard Deviation 390
|
-36.0 pg/mL
Standard Deviation 255
|
SECONDARY outcome
Timeframe: baseline, after 4 weeks of treatmentChange 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.
Outcome measures
| Measure |
Pacing Off
n=29 Participants
Subjects who received pacing off in either the first or last 4 weeks of the study
|
Pacing on
n=29 Participants
Subjects who received pacing on either the first or last 4 weeks of the study
|
|---|---|---|
|
Change in Kansas City Cardiomyopathy Questionnaire (KCCQ) Overall Summary Score
|
4.7 score on a scale
Standard Deviation 16.4
|
3.8 score on a scale
Standard Deviation 20.2
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 4 weeksDetermined 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).
Outcome measures
| Measure |
Pacing Off
n=29 Participants
Subjects who received pacing off in either the first or last 4 weeks of the study
|
Pacing on
n=29 Participants
Subjects who received pacing on either the first or last 4 weeks of the study
|
|---|---|---|
|
Mean Peak Heart Rate (HR)
|
109 bpm
Standard Deviation 21
|
123 bpm
Standard Deviation 15
|
Adverse Events
Pacing Off
Serious events: 0 serious events
Other events: 8 other events
Deaths: 0 deaths
Pacing on
Serious events: 0 serious events
Other events: 7 other events
Deaths: 0 deaths
Pacemaker Implantation
Serious events: 1 serious events
Other events: 5 other events
Deaths: 0 deaths
Washout Period
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
| Measure |
Pacing Off
n=29 participants at risk
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.
|
Pacing on
n=29 participants at risk
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.
|
Pacemaker Implantation
n=32 participants at risk
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.
|
Washout Period
n=29 participants at risk
After first intervention, both pacing off and pacing on groups will have a 4 week washout period when the pacemaker is turned off.
|
|---|---|---|---|---|
|
Cardiac disorders
Pericardial effusion
|
0.00%
0/29 • 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.
|
0.00%
0/29 • 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.
|
3.1%
1/32 • 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.
|
0.00%
0/29 • 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
| Measure |
Pacing Off
n=29 participants at risk
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.
|
Pacing on
n=29 participants at risk
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.
|
Pacemaker Implantation
n=32 participants at risk
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.
|
Washout Period
n=29 participants at risk
After first intervention, both pacing off and pacing on groups will have a 4 week washout period when the pacemaker is turned off.
|
|---|---|---|---|---|
|
Cardiac disorders
Chest discomfort/palpitations
|
3.4%
1/29 • 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.
|
17.2%
5/29 • 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.
|
0.00%
0/32 • 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.
|
0.00%
0/29 • 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.
|
|
Cardiac disorders
Pacing lead induced tricuspid regurgitation
|
0.00%
0/29 • 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.
|
0.00%
0/29 • 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.
|
3.1%
1/32 • 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.
|
0.00%
0/29 • 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.
|
|
Cardiac disorders
Upper extremity deep venous thrombosis
|
0.00%
0/29 • 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.
|
0.00%
0/29 • 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.
|
3.1%
1/32 • 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.
|
0.00%
0/29 • 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.
|
|
Skin and subcutaneous tissue disorders
Incision site reaction
|
0.00%
0/29 • 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.
|
0.00%
0/29 • 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.
|
9.4%
3/32 • 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.
|
0.00%
0/29 • 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.
|
|
Nervous system disorders
Dizziness
|
10.3%
3/29 • 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.
|
0.00%
0/29 • 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.
|
0.00%
0/32 • 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.
|
0.00%
0/29 • 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.
|
|
General disorders
Worsening fatigue
|
6.9%
2/29 • 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.
|
3.4%
1/29 • 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.
|
0.00%
0/32 • 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.
|
0.00%
0/29 • 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.
|
|
Infections and infestations
Non pacemaker infection
|
6.9%
2/29 • 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.
|
3.4%
1/29 • 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.
|
0.00%
0/32 • 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.
|
0.00%
0/29 • 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.
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place