Baroreflex Activation Therapy in Left Ventricular Assist Device Patients Study

NCT ID: NCT06195046

Last Updated: 2025-07-23

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-07-01
• Study Completion Date: 2025-07-01

Brief Summary

This study will involve LVAD patients who have already received a clinically-indicated BAT (BAROSTIM) device. After recovery from LVAD implant, we will investigate the effects of BAT in a double-blind cross-over study design.

Detailed Description

Left ventricular assist devices (LVADs) provide a meaningful therapeutic option for patients with end-stage systolic heart failure who cannot receive cardiac transplantation. For these patients, LVADs have been shown to improve mortality, functional capacity, and quality of life [1-3]. With ever-improving technological and procedural advances, the number of LVAD implantations for patients with end-stage cardiomyopathy as bridge to transplant, recovery, or even as destination therapy continues to rise [4]. Despite the short term clinical benefits of LVAD support, studies show that deleterious neurohormonal activation does not abate after LVAD implantation and that left ventricular scarring (or fibrosis) does not regress and may worsen. Similarly, the prevalence of myocardial recovery with LVAD support has been dismally low with <1% of patients recovering to the point where their LVAD can be safely explanted. Given that the majority of patients undergoing LVAD are now doing so with a destination therapy designation, and that the median estimated survival time on LVAD support ranges from 4-6 years, the importance of therapies to maximize chances for myocardial recovery while LVAD supported is evident.

The pathophysiologic reasons underlying the lack of abrogation of sympathetic and neurohormonal signaling with LVAD support, even in the face of adequate hemodynamic support, may center around the non-pulsatile nature of the device. Markham and Levine described sympathetic nerve activity in both pulsatile and nonpuslatile LVAD patients in 2013, demonstrating that patients with nonpulsatile devices had markedly elevated muscle sympathetic nerve activity, though pulsatile LVAD patients and normal controls had similar sympathetic activity. In a sequence of experiments, the authors demonstrated that this was at least partly due to baroreceptor unloading in the nonpulsatile patients. Further studies have demonstrated that plasma norepinephrine levels remain elevated after VAD implant, as do neurohormones in the renin-angiotensin-aldosterone axis. Sympathetic neurohormone levels have been shown to correlate with clinical response to LVAD therapy (defined by significant improvement in quality of life determined by the KCCQ), with reduced B-adrenergic receptor kinase-1 and DHPG levels differentiating those with better clinical response. Further, pathologic studies pre- and post-LVAD have demonstrated an acceleration of deleterious myocardial fibrosis during LVAD support, potentially driven by sympathetic and/or RAAS signaling pathways.

As demonstrated in preclinical studies and the clinical BeAT-HF trial, autonomic modulation with baroreflex activation therapy (BAT) with the BAROSTIM NEO system reduced sympathetic signaling, leading to increased NT-proBNP, 6-minute hall walk distance (6MHW), and improved quality of life in patients with chronic systolic heart failure.

However, the role of BAT in the unique physiologic LVAD-supported state has not be characterized. Given the concerns that LVAD support by augment sympathetic and thereby RAAS signaling, and that BAT may abrogate those deleterious pathways, we propose to study the clinical and neurohormonal effects of BAT in LVAD supported patients.

Conditions

Congestive Heart Failure

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: DOUBLE

Study Groups

control (BAT off)

Baroreflex activation therapy turned off for three months

Group Type: SHAM_COMPARATOR

Baroreflex Activation Therapy (BAT)

Intervention Type: DEVICE

activation of BAROSTIM NEO system that affects autonomic modulation with BAT therapy.

treatment (BAT on)

Baroreflex activation therapy turned on for three months

Group Type: EXPERIMENTAL

Baroreflex Activation Therapy (BAT)

Intervention Type: DEVICE

activation of BAROSTIM NEO system that affects autonomic modulation with BAT therapy.

Interventions

Baroreflex Activation Therapy (BAT)

activation of BAROSTIM NEO system that affects autonomic modulation with BAT therapy.

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Age > 18 years
• LVAD patient > 3 months post implant
• Existing BAT device

Exclusion Criteria

• Presence of cardiogenic shock, respiratory failure, hypotension or unstable heart failure
• Bradycardia (resting HR <60 beats/minute)
• Presence of suspected pump thrombosis at the time of enrollment
• Presence of any significant ventricular arrhythmias at the time of enrollment

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

CVRx, Inc.

INDUSTRY

Sponsor Role: collaborator

Medical University of South Carolina

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Other Identifiers

Pro00115552

Identifier Type: -

Identifier Source: org_study_id