Study for the Treatment of Heart Failure With Preserved Ejection Fraction Associated With High Blood Pressure Using Right Atrial Pacing Controlled by the PressurePaceTM System (RelieveHFpEFII)

Early Feasibility, Randomized Crossover and Double-Blind Design, Study for the Treatment of Heart Failure With Preserved Ejection Fraction (HFpEF) Associated With Hypertension Utilizing Right Atrial Pacing Regulated by the PressurePace™ System (RelieveHFpEF-II)

This study is a prospective, double blind, self-controlled, randomized, cross-over study to evaluate the feasibility, efficacy, and safety of treating patients with Heart Failure with preserved Ejection Fraction (HFpEF) associated with hypertension using the PressurePace™ system of Right Atrial Pacing regulated by blood pressure in subjects with dual chamber pacemakers.

The objective of this study is to show that blood pressure-controlled right atrial pacing improves exercise tolerance, improves heart failure symptoms, and improves hypertension control in subjects with HFpEF associated with hypertension compared to conventional bradycardia pacing alone.

Study Overview

• Status: Completed
• Conditions: Hypertension; Heart Failure With Preserved Ejection Fraction (HFpEF)
• Intervention / Treatment: Device: BaroPacing treatment; Device: Standard treatment

Detailed Description

This study is a prospective, double blind, self-controlled, randomized, cross-over study to evaluate the feasibility, efficacy, and safety of treating patients with Heart Failure with preserved Ejection Fraction (HFpEF) associated with hypertension using the PressurePace™ system of Right Atrial Pacing regulated by blood pressure in subjects with dual chamber pacemakers. No surgery, intervention or implant will occur during this study. All subjects enrolled in the study already have a dual chamber pacemaker implanted for standard clinical indications.

The objective of this study is to show that blood pressure-controlled right atrial pacing improves exercise tolerance, improves heart failure symptoms and improves hypertension control in subjects with HFpEF associated with hypertension compared to conventional bradycardia pacing alone.

Each subject will have an office/clinic visit. Once the subject signs informed consent, the pacemaker will be interrogated by trained personnel. If all the inclusion/exclusion criteria are met, then the pacemaker will be connected to the pacemaker manufacturer's interrogation module which will be connected to the BaroPace interface. The system will run with clinical oversight in the office to determine suitability for outpatient function and subject usability. The system will then be used by the subjects for the duration of the study always with the direct supervision of a trained Clinical Research Coordinators.

Subjects that met all inclusion and exclusion criteria will be entered into the baseline phase (Day 1 to Day 7) where subjects will continue to receive their baseline antihypertensive medications while on standard baseline pacing parameters. Subjects will have at baseline screening day and day 7, 24-hour Ambulatory BP monitoring (ABPM). On Screening Day subjects will undergo a 2 D echo to assess ejection fraction, 6-Minute Walk test and a treadmill using the Modified Bruce Protocol on screening and Day 7. On Day 7, if subject has >3 lbs. weight loss, or >10 mmHg drop in SBP or >5 mmHg drop in DBP (mean of the past 3 12-hour BP readings at home) or is unable to tolerate at least 3 minutes on the Modified Bruce Protocol treadmill, or walk at least 225 meters during the 6-Minute Walk test, the subject will be discontinued from the study. Subjects that continue in the study will be randomized into two groups (8 subjects in each group), group 1 will use BaroPacing for the first 3 weeks (day 8 to day 28) and then switch to standard treatment for another 3 weeks (day 29 to day 49). Group 2 will use standard treatment for the first 3 weeks (day 8 to day 28) and then switch to BaroPacing for another 3 weeks (day 29 to day 49). Total study duration for a subject will be 7 weeks (49 +/- 5 days).

At the end of 49 days, the subject will return to the office/clinic, the external system components will be disconnected, and the subject's pacemaker will be returned to pre-study parameters.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• India
  • Rajasthan
    • Jaipur, Rajasthan, India, 302039
      • Maharaja Agrasen Superspeciality Hospital, Clinical Research Department, Basement, Main Building, Room No-09, Sector-07, Agrasen Aspatal Marg, Central Spine, Vidyadhar Nagar,
    • Jaipur, Rajasthan, India, 303702
      • Dr. C. M. Chopra Hospital & Heart Care Centre
  • Uttar Pradesh
    • Kanpur, Uttar Pradesh, India, 208002
      • L.P.S. Institute of Cardiology, G.S.V.M Medical College

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Have a Pacetronix dual chamber pacemaker implanted for > 2 weeks that is more than 6 months from ERI (elective replacement indicator).
2. Ages: Adult subjects > 35 years and < 90 of age.
3. Have heart failure with preserved ejection fraction defined as ejection fraction > 45 percent.
4. Have hypertension (SBP >135 mmHg) within 30 days before the start of screening, despite at least one or more medication for the treatment of hypertension.
5. Screening average right atrial pacing < 50% and average intrinsic/pacing heart rate < 70 bpm over the previous clinical monitoring period of the pacemaker diagnostics of at least 14 days
6. Blood pressure of no less than 135 systolic and a diastolic blood pressure no less than 85 mm Hg at initial screening over 3 readings in 30 minutes in the sitting position, in the left arm.
7. Able to tolerate at least 3 minutes of a Modified Bruce Protocol Treadmill
8. Physically capable and willing to perform repeated 6-minute walk tests associated with the study, and a baseline distance of at least 225 meters. Symptoms limiting the duration of the 6-minute walk test must be due to heart failure alone.
9. Willing and able to sign consent.
10. Stable medications for Hypertension for at least 4 weeks prior to screening.

Exclusion Criteria:

1. A resting SBP > 170 mmHg, or < 130 SBP at screening average over 3 readings in 30 minutes. The readings will be taken with the blood pressure cuff on the subject's left arm while seated after at least ten minutes of rest. Consecutive readings will be taken at least 10 minutes apart.
2. A resting DBP > 120 mmHg, or < 80 at screening average over 3 measurements in 30 minutes.
3. Physical or psychological condition which would impair study participation.
4. End Stage Renal Disease on haemodialysis
5. Indications for emergency surgery at time of screening or planned surgery before the 49-day follow-up
6. Pregnant or breast-feeding.
7. Hospitalized in the prior six months for a heart attack, stroke, or TIA, or have a history of blood-pressure related syncope in last 6 months.
8. Have a pacemaker that is currently the subject of a manufacturer's recall or regulatory advisory of malfunction.
9. Prone to atrial or ventricular arrhythmias with altered pacing.
10. Unstable from a cardiovascular standpoint, such as on-going chest pain, the diagnosis of heart failure with reduced EF, or who report being ill or otherwise uncomfortable, medically, or psychologically at the time of study.
11. Unable to interact and execute commands with the BaroPace modules during the screening phase.
12. Taking short acting Nifedipine or Clonidine or taking ISA Beta Blockers; Acebutolol, Pindolol, Sectral or Visken

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: BaroPacing treatment; Group 1 will use BaroPacing for the first 3 weeks (day 8 to day 28) and then switch to standard treatment for another 3 weeks (day 29 to day 49).	Device: BaroPacing treatment; BaroPacing for the first 3 weeks (day 8 to day 28) and then crossover to standard treatment for another 3 weeks (day 29 to day 49).
Active Comparator: Standard treatment; Group 2 will use standard treatment for the first 3 weeks (day 8 to day 28) and then switch to BaroPacing for another 3 weeks (day 29 to day 49).	Device: Standard treatment; Individual Standard treatment as prescribed by the Physician to each subject for the first 3 weeks (day 8 to day 28) and then crossover to BaroPacing for another 3 weeks (day 29 to day 49).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Modified Bruce Protocol treadmill total exercise time	At Screening Day, Day 7, Day 28, Day 49
Absence of Related Serious Adverse events	From screening to end of study- Day 49

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
NYHA class position		At Screening Day, Day 7, Day 28 and Day 49
Change from baseline of the total distance in 6 minutes	The change from baseline on the 7th day of the total distance in 6 minutes, in meters, that the patient can walk compared to 6 minutes walked on day 28 and 49. Baseline will be compared to both treatment and control. The 6-minute walk test will be performed according to the American Thoracic Society guidelines.	At Screening Day, Day 7, Day 28, Day 49
Changes in The Minnesota Living with Heart Failure Questionnaire administered	The Minnesota Living with Heart Failure Questionnaire is a quality-of-life questionnaire. At every 12-hour interval during the study the subject will be asked on the computer tablet a few questions, asking how much you're the treatment has affected the enrolled subject's life on a scale of 0, 1, 2, 3, 4 or 5. Zero denoting no adverse affect on life and 5 denoting very much adverse affect on life.	At Screening Day, Day 7, Day 28, Day 49
Quality of life questions for measuring changes in sense of well-being during intervals of perceived changes in RA pacing	It is a 3 point scale, Better=2, same=1 worse=0 reduction of Afib: How many episodes in a 21 day period.	Every 12 hours throughout the 21 day treatment duration.
Systolic blood pressure change from baseline	At least 5 mmHg drop in systolic blood pressure change from baseline	after 21 days or less of treatment
Proportion of subjects with a Systolic blood pressure drop	Proportion of subjects with a SBP drop >= 5 mmHg	at the end of 21 days
Duration of response of Systolic blood pressure after lowering	Duration of response of SBP after lowering >= 5 mmHg	at the end of 21 days
Drop in diastolic blood pressure change from baseline	At least 3 mmHg drop in diastolic blood pressure change from baseline	after 21 days or less of treatment
Proportion of subjects with a diastolic blood pressure drop	Proportion of subjects with a DBP drop >= 3 mmHg	at the end of 21 days
Duration of response of diastolic blood pressure after lowering	Duration of response of DBP after lowering >= 3 mmHg	at the end of 21 days
Reduction in the number of antihypertensive medications	Reduction in the number of antihypertensive medications or a reduction in milligrams of one or more medications	at the end of 21 days
Reduction in atrial fibrillation	Reduction in atrial fibrillation monitored by telemetry and downloaded to PressurePace™	every 12 hour visit on screening, first 7 days, randomization to 21-day period, in final 21 days, for total of 7 weeks
Rate of intolerance to increases in right atrial pacing	Rate of intolerance to increases in right atrial pacing requiring reduction to a prior lower level of right atrial pacing	every 12 hour visit on screening, first 7 days, randomization to 21-day period, in final 21 days, for total of 7 weeks

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Feasibility of real-time closed loop programming of a pacemaker atrial rate based on controlled algorithm.	real time programming worked=1, did not work=0	every 12 hour visit on screening, first 7 days, randomization to 21-day period, and in final 21 days, for total of 7 weeks
Feasibility of subject's real-time subjective inputs as a moderator of pacemaker atrial rate function and PressurePace™	real-time inputs resulted in moderating pacemaker atrial rate worked=1, did not =0	every 12 hour visit on screening, first 7 days, randomization to 21-day period, and in final 21 days, for total of 7 weeks
Real-time closed-loop performance of commands to regulate atrial rate pacing parameters.	worked=1, did not work=0	every 12 hour visit on screening, first 7 days, randomization to 21-day period, and in final 21 days, for total of 7 weeks
Subject's report of changes in sense of well-being during intervals of increased right atrial pacing.	Reported no change=1, reported change to un-well =0	every 12 hour visit on screening, first 7 days, randomization to 21-day period, and in final 21 days, for total of 7 weeks
Subjective inputs by the subject on how he/she is feeling	Reported yes=1 reported no=0	every 12 hour visit on screening, first 7 days, randomization to 21-day period, and in final 21 days, for total of 7 weeks

Collaborators and Investigators

• Sponsor: BaroPace Inc.
• Collaborators: JSS Medical Research Inc.

Study record dates

Study Major Dates

• Study Start (Actual): August 26, 2023
• Primary Completion (Actual): April 12, 2024
• Study Completion (Actual): April 12, 2024

Study Registration Dates

• First Submitted: August 16, 2023
• First Submitted That Met QC Criteria: September 12, 2023
• First Posted (Actual): September 13, 2023

Study Record Updates

• Last Update Posted (Actual): May 17, 2024
• Last Update Submitted That Met QC Criteria: May 15, 2024
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Heart Failure; Hypertension
• Other Study ID Numbers: BP011

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No