Pacemaker Therapy for Heart Failure

(FIRE-HFpEF Trial)

Recruiting at 11 trial locations

Overseen By Scott A Sarazin

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Medtronic Cardiac Rhythm and Heart Failure

Must be taking: Heart failure medications

Disqualifiers: Atrial fibrillation, Structural heart disease, Severe COPD, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 6

105 Participants Needed

Trial Summary

What is the purpose of this trial?

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.

Will I have to stop taking my current medications?

The trial requires participants to be stable on their current heart failure medications for at least one month before joining, except for loop diuretics. This means you should continue taking your prescribed medications as directed by your doctor.

Is pacemaker therapy for heart failure safe for humans?

There is no specific safety data available for pacemaker therapy for heart failure in the provided research articles. ^{1 2 3 4 5}

How is the Pacemaker PLR ON and Pacemaker PLR + TRT ON treatment for heart failure different from other treatments?

This treatment is unique because it involves a pacemaker that not only helps regulate heart rhythm but also includes features like cardiac resynchronization therapy (CRT), which can improve heart function in patients with heart failure by ensuring the heart's chambers beat in sync. This is particularly beneficial for patients with left ventricular dysfunction, a common issue in heart failure. ^{6 7 8 9 10}

Research Team

Tom Mullen

Principal Investigator

Medtronic

Eligibility Criteria

This trial is for people with heart failure who still have normal or near-normal heart pumping function (LVEF ≥ 55%), specifically those in NYHA Functional Class I-III without severe symptoms. Participants should show signs of a thickened heart muscle and be stable on standard heart failure meds, except diuretics, for at least a month. They can't join if they need a pacemaker for other reasons, have severe chest pain during exercise, permanent A-fib, recent valve surgery, serious lung disease like COPD, very low kidney function (eGFR < 25), uncontrolled high blood pressure despite treatment, or certain types of cardiomyopathy.

Inclusion Criteria

My heart's size is within the normal range for my body size.

My heart's pumping ability is normal or above normal.

My heart condition allows me to perform daily activities with minimal to moderate difficulty.

Exclusion Criteria

I experience chest pain when I exert myself.

I have severe lung disease such as advanced COPD.

I had an aortic valve replacement less than a year ago.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline and Implantation

Baseline data collection and pacemaker implantation

6 weeks

1 visit (in-person)

Randomization and Initial Follow-up

Randomization to pacing therapy or control, with follow-up visits at 3, 6, and 9 months

9 months

3 visits (in-person)

Therapy Modification

Therapy modifications based on initial randomization; pacing therapy terminated in original group and enabled in control group

3 months

1 visit (in-person)

Final Follow-up

Final follow-up visit with therapy cessation and exit from the study

3 months

1 visit (in-person)

Treatment Details

Interventions

• Pacemaker PLR ON
• Pacemaker PLR + TRT ON

Trial Overview The FIRE-HFpEF study is testing whether special pacing therapies from pacemakers can improve the ability to exercise and overall health in patients with Heart Failure with Preserved Ejection Fraction (HFpEF). It's comparing two different pacemaker settings to see which might work better. Up to 105 participants will be randomly assigned to one of these treatments at multiple centers.

Participant Groups

Group I: Pacemaker with multiple pacing therapies enabled Experimental Treatment 1 Intervention

Device will be programmed for personalized lower rate pacing (PLR) and tachycardiac remodeling pacing (TRT).

Group II: Pacemaker with no pacing therapies enabled Active Control 1 Intervention

Device will be programmed to a non-pacing mode or an exertional rate-adaptive pacing mode with no planned pacing at rest.

Who Is Running the Clinical Trial?

Medtronic Cardiac Rhythm and Heart Failure

Lead Sponsor

Trials

206

Recruited

137,000+

Geoff Martha

Medtronic Cardiac Rhythm and Heart Failure

Chief Executive Officer since 2020

MBA from University of Minnesota

Dr. Kweli Thompson

Medtronic Cardiac Rhythm and Heart Failure

Chief Medical Officer since 2022

MD from Harvard Medical School

Findings from Research

In a study of 199 psoriasis patients on long-term biologic treatments, significant changes were observed in neutrophil counts and triglyceride levels, particularly during the first 180 days of treatment, indicating the need for careful monitoring of these parameters.

Despite recording 15 serious laboratory adverse events related to liver enzymes, only 2 cases required a change in treatment, suggesting that routine monitoring of many laboratory parameters may not be necessary during long-term biologic therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Routine Laboratory Parameter Dynamics and Laboratory Adverse Events in Psoriasis Patients on Long-term Treatment with Adalimumab, Etanercept, and Ustekinumab. Hoffmann, JH., Knoop, C., Enk, AH., et al.[2017]

Long-term safety concerns have emerged regarding TNF blocker therapy, including risks of infections, cytopenias, lymphoma, and other serious conditions, necessitating careful monitoring of patients.

Regular evaluations and tuberculin skin testing are recommended before starting TNF inhibitors to assess the risk of infections, particularly tuberculosis, ensuring the safety and efficacy of the treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Laboratory monitoring of biologic therapies. Cush, JJ., Yazici, Y.[2017]

The combination of the Micra AV pacemaker and WiSE-CRT systems allows for completely leadless cardiac resynchronization therapy, demonstrating feasibility in clinical practice.

This case report provides a 1-year follow-up on the first use of these leadless systems together in the United States, indicating potential for innovative treatment options in cardiac care.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Outcome of the First Completely Leadless Cardiac Resynchronization Therapy in the United States. Mehlhorn, D., Patel, S., Verghese, D., et al.[2023]

Biologics, including TNF, IL-12/23, and IL-17 antagonists, have been shown to be safe for both short- and long-term use, based on a review of phase 3 clinical trials and biologics registries.

While these treatments have similar safety profiles regarding infections and cardiovascular events, specific risks such as tuberculosis activation with TNF antagonists can be managed through screening, and IL-17 blockade may lead to mild infections or inflammatory bowel disease issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical Trial and Registry Data. Gooderham, M., Papp, K.[2019]

The Micra AV leadless pacemaker, approved by the FDA in early 2020, was successfully implanted in a 38-year-old female patient with a complete AV block, demonstrating its safety and efficacy in treating AV blocks.

After experiencing complications with a traditional dual chamber pacemaker, the patient was safely transitioned to the Micra AV pacemaker, suggesting it may be a viable option for young patients facing device-related issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The implantation of AV leadless pacemaker - a case report. Warwas, S., Jędrzejczyk-Patej, E., Jagosz, M., et al.[2022]

In a study of 157 pacemaker-dependent patients with left ventricular dysfunction, those with significant coronary artery disease (CAD) experienced a higher risk of appropriate shocks from CRT-defibrillators, with a shocking rate of 1 per 26 person-years compared to 1 per 362 person-years in patients without CAD.

Patients without CAD had better overall survival and fewer comorbidities, suggesting that CRT-pacemakers may be a safer and equally effective option for these patients, as they showed similar improvements in heart function without the increased risk of shocks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes in pacemaker-dependent patients upgraded from conventional pacemakers to cardiac resynchronization therapy-defibrillators. Adelstein, E., Schwartzman, D., Bazaz, R., et al.[2016]

In a study of 50 patients with unavoidable right ventricular pacing and left ventricular systolic dysfunction, cardiac resynchronization therapy (CRT) significantly improved left ventricular ejection fraction (LVEF) compared to standard RV pacing, with a median increase of 9% versus a decrease of 1.5% in the RV-PGR group after 6 months.

Patients receiving CRT also experienced better exercise capacity, improved quality of life, and lower NT-proBNP levels, along with fewer hospital days compared to those with standard RV pacing, highlighting the benefits of CRT even in patients with mild or no symptoms of heart failure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Cardiac resynchronization therapy in pacemaker-dependent patients with left ventricular dysfunction. Gierula, J., Cubbon, RM., Jamil, HA., et al.[2021]

Pacemaker therapy is widely used, with around 900,000 patients receiving treatment each year, primarily for conditions like sinus node dysfunction and atrioventricular block, which can significantly improve symptoms and quality of life.

Biventricular pacing has been shown to effectively treat advanced heart failure, particularly in patients with left bundle branch block, highlighting its role in improving survival in specific populations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Indications and recommendations for pacemaker therapy. Gregoratos, G.[2007]

Pacemakers are effective for patients with symptomatic bradyarrhythmias, complete atrioventricular (AV) block, and type II second-degree AV block, but their use in type I second-degree AV block and first-degree AV block is more controversial and generally not recommended unless specific symptoms are present.

Cardiac resynchronization therapy significantly improves outcomes in patients with severe heart failure (NYHA class III or IV) and a QRS duration of 150 milliseconds or greater, but it is not supported for patients with class I heart failure or those with a QRS duration of 120 to 150 milliseconds.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Common questions about pacemakers. Denay, KL., Johansen, M.[2014]

Biventricular resynchronization therapy significantly improves cardiac function and reduces symptoms in most patients with systolic heart failure, as evidenced by improved ejection fraction and decreased NYHA class after treatment.

In a study of 17 patients with prolonged QRS intervals and severe heart failure, the majority experienced better walking distances and reduced hospital stays, although a few patients did not respond to the treatment and two patients died from unrelated complications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Resynchronisation therapy in patients with heart failure: our results]. Milasinović, G., Jelić, V., Petrović, M., et al.[2019]

References

1. Sweden pubmed.ncbi.nlm.nih.gov

Routine Laboratory Parameter Dynamics and Laboratory Adverse Events in Psoriasis Patients on Long-term Treatment with Adalimumab, Etanercept, and Ustekinumab. [2017]

2. Italy pubmed.ncbi.nlm.nih.gov

Laboratory monitoring of biologic therapies. [2017]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Long-Term Outcome of the First Completely Leadless Cardiac Resynchronization Therapy in the United States. [2023]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Clinical Trial and Registry Data. [2019]

5. Poland pubmed.ncbi.nlm.nih.gov

The implantation of AV leadless pacemaker - a case report. [2022]

6. United States pubmed.ncbi.nlm.nih.gov

Outcomes in pacemaker-dependent patients upgraded from conventional pacemakers to cardiac resynchronization therapy-defibrillators. [2016]

7. England pubmed.ncbi.nlm.nih.gov

Cardiac resynchronization therapy in pacemaker-dependent patients with left ventricular dysfunction. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Indications and recommendations for pacemaker therapy. [2007]

9. United States pubmed.ncbi.nlm.nih.gov

Common questions about pacemakers. [2014]

10. Serbia pubmed.ncbi.nlm.nih.gov

[Resynchronisation therapy in patients with heart failure: our results]. [2019]