Clinical trial NCT05839730: Fast Induced Remodeling in Heart Failure With Preserved Ejection Fraction
Official title: Fast Induced Remodeling in Heart Failure With Preserved Ejection Fraction
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Heart Failure With Preserved Ejection Fraction
Concentric Hypertrophy
Lead sponsor: Medtronic Cardiac Rhythm and Heart Failure
Sponsor class: INDUSTRY
First posted: 2023-05-03
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Intervention model description: Eligible subjects will have enrollment data collected, including a blood draw. 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.
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: Through study completion, projected for three years until last subject last 12-month visit.
measure: 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.
timeFrame: Through study completion, projected for three years until last subject last 12-month visit.
measure: Characterize the durability of cardiac remodeling changes and assess the safety and tolerability of TRT + PLR.
timeFrame: Through study completion, projected for three years until last subject last 12-month visit.
Secondary outcomes:
Other outcomes:
Locations:
city: Naples
country: United States
facility: NCH Heart Institute
state: Florida
city: O'Fallon
country: United States
facility: Prairie Education and Research Cooperative-St. Elizabeth's
state: Illinois
city: Springfield
country: United States
facility: Prairie Education and Research Cooperative-St. John's
state: Illinois
city: Kansas City
country: United States
facility: University of Kansas Medical Center
state: Kansas
city: Durham
country: United States
facility: Duke University
state: North Carolina
city: Oklahoma City
country: United States
facility: Oklahoma Heart Hospital
state: Oklahoma
city: Dallas
country: United States
facility: Dallas VA Medical Center
state: Texas
city: Houston
country: United States
facility: Houston Methodist Research Institute
state: Texas
city: Burlington
country: United States
facility: The University of Vermont Medical Center
state: Vermont
Study officials:
References: