Trial Outcomes & Findings for Restoration of Chronotropic Competence in Heart Failure Patients With Normal Ejection Fraction (NCT NCT00670111)

Last Updated: 2017-05-19

Results Overview

Randomized therapy order cross-over comparison at 1 month post-implant. Each patient evaluated for endpoint with and without RAP therapy at this time.

Recruitment status

TERMINATED

Study phase

Target enrollment

32 participants

Primary outcome timeframe

1 month post implant

Results posted on

2017-05-19

Participant Flow

Following enrollment, patients were had an exercise test to determine chronotropic incompetence (CI). If patients were not CI, they were deemed a Testing Failure and withdrawn from the study. CI patients that were then implanted with a pacemaker were randomized to the order of their Rate Adaptive Pacing therapy for the 2 one month exercise tests.

Participant milestones

Participant milestones
Measure	Rate Adaptive Pacing (RAP) On Then Off Rate Adaptive Pacing (RAP) On for first cardiopulmonary exercise test (CPX) at one month, then RAP-Off for second CPX at one month.	Rate Adaptive Pacing (RAP) Off Then On Rate Adaptive Pacing (RAP) Off for first cardiopulmonary exercise test (CPX) at one month, then RAP-On for second CPX at one month.	Non-Randomized Patients Only implanted patients were randomized. All other patients fall into this group.
Enrollment to One Month STARTED	5	8	19
Enrollment to One Month COMPLETED	4	8	0
Enrollment to One Month NOT COMPLETED	1	0	19
One Month Period A STARTED	4	8	0
One Month Period A COMPLETED	4	8	0
One Month Period A NOT COMPLETED	0	0	0
One Month Period B STARTED	4	8	0
One Month Period B COMPLETED	4	8	0
One Month Period B NOT COMPLETED	0	0	0
One Month to Six Months STARTED	4	8	0
One Month to Six Months COMPLETED	4	8	0
One Month to Six Months NOT COMPLETED	0	0	0
Six Months to Twelve Months STARTED	4	8	0
Six Months to Twelve Months COMPLETED	4	8	0
Six Months to Twelve Months NOT COMPLETED	0	0	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Rate Adaptive Pacing (RAP) On Then Off Rate Adaptive Pacing (RAP) On for first cardiopulmonary exercise test (CPX) at one month, then RAP-Off for second CPX at one month.	Non-Randomized Patients Only implanted patients were randomized. All other patients fall into this group.
Enrollment to One Month Testing Failure	0	13
Enrollment to One Month Ebrolled Patients but not Implanted	0	6
Enrollment to One Month Physician Decision	1	0

Baseline Characteristics

Restoration of Chronotropic Competence in Heart Failure Patients With Normal Ejection Fraction

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rate Adaptive Pacing (RAP) On Then Off n=5 Participants Rate Adaptive Pacing (RAP) On for first cardiopulmonary exercise test (CPX) at one month, then RAP-Off for second CPX at one month.	Rate Adaptive Pacing (RAP) Off Then On n=8 Participants Rate Adaptive Pacing (RAP) Off for first cardiopulmonary exercise test (CPX) at one month, then RAP-On for second CPX at one month.	Non-Randomized Patients n=19 Participants Only implanted patients were randomized. All other patients fall into this group.	Total n=32 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=93 Participants	0 Participants n=4 Participants	0 Participants n=27 Participants	0 Participants n=483 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=93 Participants	2 Participants n=4 Participants	5 Participants n=27 Participants	8 Participants n=483 Participants
Age, Categorical >=65 years	4 Participants n=93 Participants	6 Participants n=4 Participants	14 Participants n=27 Participants	24 Participants n=483 Participants
Age, Continuous	68.4 years STANDARD_DEVIATION 7.1 • n=93 Participants	65.8 years STANDARD_DEVIATION 12.1 • n=4 Participants	68.1 years STANDARD_DEVIATION 11.0 • n=27 Participants	67.6 years STANDARD_DEVIATION 10.5 • n=483 Participants
Sex: Female, Male Female	3 Participants n=93 Participants	5 Participants n=4 Participants	10 Participants n=27 Participants	18 Participants n=483 Participants
Sex: Female, Male Male	2 Participants n=93 Participants	3 Participants n=4 Participants	9 Participants n=27 Participants	14 Participants n=483 Participants
Region of Enrollment United States	5 participants n=93 Participants	8 participants n=4 Participants	19 participants n=27 Participants	32 participants n=483 Participants

PRIMARY outcome

Timeframe: 1 month post implant

Population: The following were required for a patient's dataset to be included in the analysis: 1. 2 CPX tests had to be performed at 1M (RAP On \& RAP Off), 2. Each 1M CPX test had to result in RER ≥ 1.05, 3. Trending data from the disk had to have been obtained during each 1M CPX test.

Randomized therapy order cross-over comparison at 1 month post-implant. Each patient evaluated for endpoint with and without RAP therapy at this time.

Outcome measures

Outcome measures
Measure	Rate Adaptive Pacing (RAP) On at One Month n=6 Participants Rate Adaptive Pacing (RAP) On for cardiopulmonary exercise test (CPX) at one month.	Rate Adaptive Pacing (RAP) Off at One Month n=6 Participants Rate Adaptive Pacing (RAP) Off for cardiopulmonary exercise test (CPX) at one month.
Peak Volume of Oxygen Uptake (Peak VO2) - Rate Adaptive Pacing (RAP) On at One Month vs. Rate Adaptive Pacing (RAP) Off at One Month.	12.47 ml/kg/min Standard Deviation 2.02	12.79 ml/kg/min Standard Deviation 2.14

SECONDARY outcome

Timeframe: 6 months post implant

Population: The following were required for a patient's dataset to be included in the analysis: 1. 2 CPX tests had to be performed (1M with RAP Off, 6M with RAP On \[RAP was On from 1M to 6M\]), 2. Each CPX test had to result in RER ≥ 1.05, 3. Trending data from the disk had to have been obtained during each CPX test.

Each patient had RAP therapy On from one through six months. This endpoint evaluated Peak VO2 measured at 6 months (RAP On) vs. Peak VO2 measured at 1 month without RAP therapy (RAP Off).All participants were "RAP On" for months 1 through 6. All participants were 'Rap On' for months 6 to 12.

Outcome measures

Outcome measures
Measure	Rate Adaptive Pacing (RAP) On at One Month n=4 Participants Rate Adaptive Pacing (RAP) On for cardiopulmonary exercise test (CPX) at one month.	Rate Adaptive Pacing (RAP) Off at One Month n=4 Participants Rate Adaptive Pacing (RAP) Off for cardiopulmonary exercise test (CPX) at one month.
Peak Volume of Oxygen Uptake (Peak VO2) - Rate Adaptive Pacing (RAP) On at Six Months vs. Rate Adaptive Pacing (RAP) Off at One Month.	12.04 ml/kg/min Standard Deviation 1.74	13.09 ml/kg/min Standard Deviation 2.35

Adverse Events

All Implanted Patients

Serious events: 7 serious events

Other events: 10 other events

Deaths: 0 deaths

Non-Randomized Patients

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Other adverse events
Measure	All Implanted Patients n=13 participants at risk All patients from the RAP On then Off group and from the RAP Off then On group.	Non-Randomized Patients n=19 participants at risk Only implanted patients were randomized. All other patients fall into this group. Adverse events were collected for all subjects, also for non-randomized patients.
Surgical and medical procedures Adverse reaction - Rash from ECG leads	7.7% 1/13 • Number of events 1 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Cardiac disorders Atrial flutter	15.4% 2/13 • Number of events 2 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Cardiac disorders Chest pain	23.1% 3/13 • Number of events 3 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Cardiac disorders Chest pain - due to acid reflux	7.7% 1/13 • Number of events 1 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Respiratory, thoracic and mediastinal disorders Coughing, Shortness of Breath	7.7% 1/13 • Number of events 1 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Musculoskeletal and connective tissue disorders Fibromyalgia	7.7% 1/13 • Number of events 1 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Cardiac disorders Heart Failure	15.4% 2/13 • Number of events 4 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Skin and subcutaneous tissue disorders Integumentary - Herpes zoster	7.7% 1/13 • Number of events 1 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Surgical and medical procedures Integumentary - Skin reaction to adhesive	7.7% 1/13 • Number of events 1 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Cardiac disorders Myocardial infarction	7.7% 1/13 • Number of events 1 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Cardiac disorders Oversensing, Right Atrial	7.7% 1/13 • Number of events 1 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Cardiac disorders Rapid heart rate	7.7% 1/13 • Number of events 1 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.

Additional Information

Elke Sommerijns

Boston Scientific

Phone: +32 479 76 71 56

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: OTHER

Measure	All Implanted Patients n=13 participants at risk All patients from the RAP On then Off group and from the RAP Off then On group.	Non-Randomized Patients n=19 participants at risk Only implanted patients were randomized. All other patients fall into this group. Adverse events were collected for all subjects, also for non-randomized patients.
Vascular disorders Cerebrovascular accident (CVA)	7.7% 1/13 • Number of events 1 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Musculoskeletal and connective tissue disorders Chronic cervical spondylosis	7.7% 1/13 • Number of events 1 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Cardiac disorders Coronary Artery Disease	15.4% 2/13 • Number of events 2 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Gastrointestinal disorders Gastrointestinal bleed	7.7% 1/13 • Number of events 1 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Renal and urinary disorders Genitourinary	7.7% 1/13 • Number of events 1 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Cardiac disorders Heart Failure	30.8% 4/13 • Number of events 7 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Blood and lymphatic system disorders Hematological - Anemia	7.7% 1/13 • Number of events 2 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Cardiac disorders Hypertension	15.4% 2/13 • Number of events 2 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Skin and subcutaneous tissue disorders Integumentary	7.7% 1/13 • Number of events 1 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Musculoskeletal and connective tissue disorders Knee replacement	7.7% 1/13 • Number of events 1 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Cardiac disorders Lead Dislodgment, Right Atrial	7.7% 1/13 • Number of events 1 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Cardiac disorders Myocardial infarction	7.7% 1/13 • Number of events 1 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Cardiac disorders Nonsustained ventricular tachycardia (NSVT)	7.7% 1/13 • Number of events 1 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Respiratory, thoracic and mediastinal disorders Pneumonia, lingular	7.7% 1/13 • Number of events 1 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.
Cardiac disorders Rate response inappropriate - Pulse generator	7.7% 1/13 • Number of events 1 • Entire study (twelve months) Adverse events were collected for all enrolled patients.	0.00% 0/19 • Entire study (twelve months) Adverse events were collected for all enrolled patients.