Fast Induced Remodeling in Heart Failure With Preserved Ejection Fraction (FIRE-HFpEF)

FIRE-HFpEF is a multi-center, prospective, randomized, single-blinded, clinical feasibility study. This study will enroll up to 105 subjects with heart failure with preserved ejection fraction in the United States. Data will be collected to evaluate whether pacing therapies can lead to improvements in exercise capacity and health status of subjects.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure With Preserved Ejection Fraction; Concentric Hypertrophy
• Intervention / Treatment: Device: Pacemaker PLR + TRT ON; Device: Pacemaker non-pacing mode or an exertional rate-adaptive pacing mode with no planned pacing at rest.

Detailed Description

After enrollment, baseline data will be collected, and subjects will then have a pacemaker implanted. After 6 weeks, subjects will have a follow up visit with a blood draw and a cardiac MRI. At this visit, subjects will be randomized 2:1 for pacing therapy or as a control (programmed into either a non-pacing mode or an exertional rate-adaptive pacing mode with no planned pacing at rest). After 3, 6 and 9 months after randomization, subjects will return for a follow up visit. At the 9-month visit therapy modifications will be made based on initial pacing randomization assignment: pacing therapy will be terminated in the original therapy group and enabled in the control group. After an additional 3-months of follow-up, subjects will return for their final visit, therapies will be disabled in all subjects and subjects will be exited. Echocardiographic, functional, and health status endpoints will be collected and analyzed to assess therapy efficacy.

• Study Type: Interventional
• Enrollment (Estimated): 105
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Scott A Sarazin; Phone Number: 763-526-2817; Email: scott.a.sarazin@medtronic.com

Study Locations

• United States
  • Florida
    • Naples, Florida, United States, 34102
      • Recruiting
      • NCH Heart Institute
      • Contact: Dinesh Sharma, MD
  • Illinois
    • O'Fallon, Illinois, United States, 62269
      • Recruiting
      • Prairie Education and Research Cooperative-St. Elizabeth's
      • Contact: Ziad Issa, MD
    • Springfield, Illinois, United States, 62769
      • Recruiting
      • Prairie Education and Research Cooperative-St. John's
      • Contact: Ziad Issa, MD
  • Kansas
    • Kansas City, Kansas, United States, 66160
      • Recruiting
      • University of Kansas Medical Center
      • Contact: Seth Sheldon, MD
  • North Carolina
    • Durham, North Carolina, United States, 27708
      • Recruiting
      • Duke University
      • Contact: Daniel Friedman, MD
  • Oklahoma
    • Oklahoma City, Oklahoma, United States, 73120
      • Recruiting
      • Oklahoma Heart Hospital
      • Contact: Charles Te, MD
  • Texas
    • Houston, Texas, United States, 77030
      • Recruiting
      • Houston Methodist Research Institute
      • Contact: Miguel Valderrabano, MD
  • Vermont
    • Burlington, Vermont, United States, 05401
      • Recruiting
      • The University of Vermont Medical Center
      • Contact: Nicole Habel, MD

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Diagnosis of Heart Failure, Left Ventricular Ejection Fraction (LVEF) ≥ 55% (this and other measurements must be made within the last year).
• New York Heart Association (NYHA) Functional Class I-III
• Stable on guideline-directed medical therapy (GDMT) heart failure medications as determined by the investigator, for at least 1 month, with the exception of loop diuretic therapy. GDMT should be in accordance with current American Heart Association (AHA)/American College of Cardiology (ACC)/Heart Failure Society of America (HFSA) Guidelines and include consideration of Sodium/glucose cotransporter-2 inhibitors (SGLT2i) therapy.
• V End Diastolic Volume indexed to body surface area (BSA) ≤ 80 mL/m^2.

• Concentric remodeling or concentric hypertrophy defined as at least one of the following criteria:

  • Left ventricular (LV) posterior or lateral wall thickness > 11mm
  • Relative wall thickness (RWT) > 0.42
  • Male and LV mass indexed to BSA ≥115 g/m2
  • Male and LV mass indexed to height ≥ 49.2 g/m2.7
  • Female and LV mass indexed to BSA ≥ 95 g/m2
  • Female and LV mass indexed to height ≥ 46.7 g/m2.7

Exclusion Criteria:

• Unable or unwilling to undergo contrast MRI.
• Class I indication for permanent pacing, except for symptomatic chronotropic incompetence
• Current permanent or persistent Atrial fibrillation (A-fib)
• Structural heart disease requiring intervention
• Aortic valve replacement procedure less than 12 months prior to enrollment
• Known pericardial constriction, genetic hypertrophic cardiomyopathy, or infiltrative cardiomyopathy
• Severe aortic or mitral valve disease, defined as severe regurgitation or a valve area < 1cm^2
• Exertional angina
• Severe pulmonary disease including severe Chronic obstructive pulmonary disease (COPD) (i.e., requiring home oxygen, chronic nebulizer therapy, or chronic oral steroid therapy or hospitalized for pulmonary decompensation within 12 months)
• Estimated glomerular filtration rate (eGFR) < 25 ml/min/1.73m^2 as calculated by the Modification in Diet in Renal Disease (MDRD) formula
• Uncontrolled blood pressure, defined as systolic pressure outside the range of 100 to 160 mmHg despite anti-hypertensive medication.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Pacemaker with multiple pacing therapies enabled; Device will be programmed for personalized lower rate pacing (PLR) and tachycardiac remodeling pacing (TRT).	Device: Pacemaker PLR + TRT ON; RAMware modified implantable pulse generator (IPG) with personalized lower rate (PLR) and tachycardia remodeling therapy (TRT) ON
Active Comparator: Pacemaker with no pacing therapies enabled; Device will be programmed to a non-pacing mode or an exertional rate-adaptive pacing mode with no planned pacing at rest.	Device: Pacemaker non-pacing mode or an exertional rate-adaptive pacing mode with no planned pacing at rest.; RAMware modified implantable pulse generator (IPG)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
characterize the effect of TRT + PLR on cardiac structure. LV mass, LVEDV, LVESV, and wall thickness which will be collected at baseline, 3-month, 6-month, 9-month, and 12-month visits.		Through study completion, projected for three years until last subject last 12-month visit.
Characterize the effect of pacing therapies on health status, defined as change in the Minnesota Living with Heart Failure Questionnaire (MLHFQ) from baseline to 3, 6, and 9 months.	The Minnesota Living with Heart Failure Questionnaire (MLHFQ) is a validated patient-oriented measure of the adverse effects of heart failure on a patient's life. Each of the 21 questions are scored on a 6-point Likert Scale (0 to 5), the total score could range from 0 to 105, with higher scores indicating more significant impairment in health-related quality of life.	Through study completion, projected for three years until last subject last 12-month visit.
Characterize the durability of cardiac remodeling changes and assess the safety and tolerability of TRT + PLR.		Through study completion, projected for three years until last subject last 12-month visit.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Characterize durability of changes in cardiac structure and/or health & functional status following the modification or cessation of pacing therapies at 7, 10, and 12 months.	Assess the number of crossovers and/or patients with treatment-related adverse events as assessed by Common Terminology Criteria for Adverse Events v4.0 (CTCAE).	Through study completion, projected for three years until last subject last 12-month visit.
Characterize the impact of AVNS therapy on changes in serum biomarkers: Tumor Necrosis Factor (TNF-α), Interleukin 6 (IL-6) Interleukin 1 beta (IL-1β) from pre-implant to 0 hours, 4 hours, 24 hours and 6 weeks post-implant.		From pre-implant to 0 hours, 4 hours, 24 hours and 6 weeks post-implant

Collaborators and Investigators

• Sponsor: Medtronic Cardiac Rhythm and Heart Failure
• Investigators: Study Director: Tom Mullen, Medtronic

Study record dates

Study Major Dates

• Study Start (Actual): September 11, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027

Study Registration Dates

• First Submitted: March 1, 2023
• First Submitted That Met QC Criteria: April 20, 2023
• First Posted (Actual): May 3, 2023

Study Record Updates

• Last Update Posted (Actual): April 27, 2026
• Last Update Submitted That Met QC Criteria: April 23, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Pathological Conditions, Anatomical; Heart Diseases; Heart Failure; Hypertrophy
• Other Study ID Numbers: MDT20060

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: Yes
• product manufactured in and exported from the U.S.: No