Fast Induced Remodeling in Heart Failure With Preserved Ejection Fraction

Heart Failure With Preserved Ejection Fraction Clinical Trial

— FIRE-HFpEF  

Official title:

Fast Induced Remodeling in Heart Failure With Preserved Ejection Fraction

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT05839730
• Other study ID #: MDT20060
• Status: Suspended
• Phase: N/A
• Start date: September 26, 2023
• Est. completion date: January 2026

Study information

• Verified date: April 2024
• Source: Medtronic Cardiac Rhythm and Heart Failure
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Description:

After enrollment, baseline data will be collected, and subjects will then have a pacemaker implanted. Subjects will then be randomized 1:1 to either the Atrial Ventricular Node Stimulation (AVNS) therapy or the control group, that will be applied for 24 hours and discontinued at the end of the 24-hour period. Serum biomarkers will be collected and analyzed. After 6 weeks, subjects will be randomized to either the full pacing therapy (TRT + PLR on) or the control group. At 7 months therapy modifications will be made based on initial pacing randomization assignment (full pacing therapy or modified pacing therapy), and a new randomization which applies pacing therapies (either full pacing therapy or modified pacing therapy) to all subjects will be applied. At 10 months all pacing therapy will have a final adjustment and subjects will be evaluated for their final visit at 12-months and exited from the study. Echocardiographic, functional, and health status endpoints will be collected and analyzed to assess therapy efficacy.

Recruitment information / eligibility

• Status: Suspended
• Enrollment: 105
• Est. completion date: January 2026
• Est. primary completion date: January 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Heart Failure
• Heart Failure With Preserved Ejection Fraction
• Hypertrophy

Intervention

Device:
• Pacemaker PLR + TRT ON
RAMware modified implantable pulse generator (IPG) with personalized lower rate (PLR) and tachycardia remodeling therapy (TRT) on
• Pacemaker PLR ON
RAMware modified implantable pulse generator (IPG) with personalized lower rate (PLR) on

Locations

Country	Name	City	State
United States	Emory University Hospital	Atlanta	Georgia
United States	University of Kansas Medical Center	Kansas City	Kansas
United States	NCH Heart Institute	Naples	Florida
United States	Prairie Education and Research Cooperative	Springfield	Illinois

Sponsors (1)

Lead Sponsor	Collaborator
Medtronic Cardiac Rhythm and Heart Failure

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in left ventricular volumes as assessed by cardiac MRI compared from baseline to 7,10, and 12-month follow-up visits.		Through study completion, projected for three years until last subject last 12-month visit.
Primary	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, 7, 10, and 12 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.
Primary	Characterize the effect of pacing therapies on functional status, defined as change in 6-minute walk test from baseline to 7, 10, and 12 months.		Through study completion, projected for three years until last subject last 12-month visit.
Primary	Characterize the effect of pacing therapies on functional status, defined as change in device-measured accelerometer data from baseline to 3, 7, 10, and 12 months.		Through study completion, projected for three years until last subject last 12-month visit.
Secondary	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.
Secondary	Characterize the impact of AVNS therapy on changes in serum biomarkers: Tumor Necrosis Factor (TNF-a), Interleukin 6 (IL-6) Interleukin 1 beta (IL-1ß) 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