Barostim-Enabled NEurohormonal Intervention For Improving Treatment of Heart Failure (BENEFIT-HF)

Barostim-Enabled NEurohormonal Intervention For Improving Treatment of Heart Failure (BENEFIT-HF)

The purpose of BENEFIT-HF is to demonstrate the safety and effectiveness of Baroreflex Activation Therapy (BAT) with the Barostim System in participants with heart failure, defined as NYHA Functional Class II or III, LVEF < 50% and NT-proBNP < 5,000 pg/mL despite being treated with Guideline-Directed Medical Therapies (medications and devices). It includes demonstration that treatment with the Barostim System, relative to usual care medical management, reduces the rate of all-cause mortality and Heart Failure Morbidity (Cardiac Transplant, Durable LVAD, or Worsening Heart Failure Events).

Study Overview

• Status: Enrolling by invitation
• Conditions: Heart Failure; Heart Failure NYHA Class II; Heart Failure NYHA Class III
• Intervention / Treatment: Device: Barostim System; Other: Usual care medical management

• Study Type: Interventional
• Enrollment (Estimated): 2500
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Alabama
    • Mobile, Alabama, United States, 36608
      • Cardiology Associates of Mobile
  • Florida
    • Tallahassee, Florida, United States, 32308
      • Tallahassee Research Institute
    • Tampa, Florida, United States, 33614
      • BayCare Health Systems
  • South Dakota
    • Sioux Falls, South Dakota, United States, 57108
      • North Central Heart

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Age 18 years or above
2. NYHA Functional Class II or III heart failure symptoms at the time of screening
3. Left ventricular ejection fraction < 50% within 6 months of consent

4. Heart failure accompanied by either:

   • Screening local lab NT-proBNP ≥ 400 AND < 5,000 pg/mL or a BNP ≥100 AND < 1,250 pg/mL, adjusted for BMI in a stable outpatient setting OR
   • A documented Worsening Heart Failure Event in the 6 months prior to or concurrent with consent, AND an NT-proBNP < 5,000 pg/mL or BNP < 1,250 pg/mL, adjusted for BMI in a stable outpatient setting.

   Note: If participant is taking sacubitril/valsartan (i.e. Entresto®), NT-proBNP must be used for screening eligibility. NT-proBNP and BNP to be adjusted for BMI using a 4% reduction per BMI unit over 25 kg/m2.

5. On optimal, maximally tolerated Guideline Directed Medical Therapy (GDMT) (medications and devices) per current country specific guidelines (e.g. US follows AHA/ACC guidelines, Germany follows DGK/ESC guidelines) for the treatment of heart failure, when appropriate, throughout screening/baseline evaluation and for at least 4 weeks prior to consent:

   • No more than a 100% increase or a 50% decrease of the dosage of any one medication other than an oral diuretic.
   • Medication changes within a drug class are allowed as long as the equivalent dosage is within the limits specified above.
   • Unrestricted changes in oral diuretics are allowed.
   • For participants with LVEF between 40-50%, SGLT2 inhibitors and mineralocorticoid receptor antagonists (MRAs) are encouraged and should be initiated before consent when possible.
6. Six-minute hall walk (6MHW) ≥ 100 m AND ≤ 450 m within 15 days after consent.
7. If female and of childbearing potential, must have a negative pregnancy test within 15 days after consent.
8. Be an appropriate candidate for the trial and the surgical procedure as determined by the investigator or designee and the surgeon.
9. Have signed an informed consent form for participation in this trial.

Exclusion Criteria:

1. Any contraindications to Barostim as noted in Instructions for Use.
2. An existing device which contraindicates Barostim specifically or unipolar therapy in general.

3. Advanced heart failure defined by any of the following:

   • AHA/ACC Stage D heart failure.
   • Two or more NT-proBNP results >5,000 pg/mL or BNP >1,250 pg/mL in a stable outpatient setting within 3 months prior to consent. If participant is taking sacubitril/valsartan (i.e. Entresto®), NT-proBNP must be used for screening eligibility.
   • Current or prior continuous or intermittent intravenous positive inotrope therapy.
   • Has received, is receiving, or scheduled to receive LVAD therapy.
   • Solid organ or hematologic transplant or currently being evaluated for cardiac transplant.
4. Serum estimated glomerular filtration rate (eGFR) < 20 mL/min/1.73 m2 or has end-stage renal disease.
5. Recurring symptomatic hypotension.
6. Life expectancy less than one year.

7. An inappropriate trial candidate as evidenced by at least one of the following:

   • Has received or is receiving chronic dialysis.
   • Is within WHO groups 1, 3, 4, or 5 pulmonary hypertension.
   • Severe COPD or severe restrictive lung disease requiring chronic oral steroid use or any oxygen use.
   • Heart failure secondary to a reversible cause, such as cardiac structural valvular disease, acute myocarditis and pericardial constriction.
   • Active malignancy with the exception of non-melanoma skin cancers.
   • Infiltrative cardiomyopathy (e.g. cardiac amyloidosis).
   • Any other serious medical condition that may adversely affect the safety of the participant or validity of the trial, in the opinion of the investigator.

8. Any of the following within 3 months prior to consent:

   • Myocardial infarction
   • Unstable angina
   • Percutaneous coronary intervention (e.g. PTCA)
   • Cerebral vascular accident or transient ischemic attack
   • Cardiac arrest
   • Surgical cardiac intervention (e.g., CABG, cardiac ablation, valve replacement, CRT/ICD implantation, IPG battery replacements)
9. Surgery planned to occur within 45 days of the Barostim implant procedure. This includes pacemaker or ICD implants or battery replacements.
10. Enrolled and active in another clinical trial (e.g. device, pharmaceutical, or biological) unless approved by the CVRx Clinical Research department.
11. Unable or unwilling to fulfill the Protocol medication compliance and follow-up requirements, for reasons including but not limited to an unresolved history of alcohol or substance abuse or psychiatric disorder. Participant is a member of a vulnerable population who, in the judgment of the investigator, is unable to give Informed Consent for reasons of incapacity, immaturity, adverse personal circumstances or lack of autonomy. This may include individuals with mental disability, persons in nursing homes, impoverished persons, persons in emergency situations, homeless persons, nomads, refugees, and those permanently incapable of giving informed consent. Vulnerable populations also include university students, subordinate hospital and laboratory personnel, employees of the Sponsor, members of the armed forces, and persons kept in detention.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Device Arm; Participants will receive Baroreflex Activation Therapy (BAT) with an implanted Barostim System in addition to usual care medical management.	Device: Barostim System; Baroreflex Activation Therapy (BAT) using the Barostim System
Active Comparator: Control Arm; Participants will receive usual care medical management alone with no Barostim System device implant.	Other: Usual care medical management; Usual care medical management alone - no device implant

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Effectiveness Endpoint	Composite of all-cause mortality and Heart Failure Morbidity, defined as Cardiac Transplant, Durable LVAD, or Worsening Heart Failure Events, assessed through 24 months of follow-up.	Through 24-months follow-up
Primary Safety Endpoint	The event-free rate of all system- and procedure-related Major Adverse Neurological and Cardiovascular Events (MANCE) occurring within 180 days of the device implant, assessed among participants who were randomized to the Device Arm and in whom an implant has been achieved or attempted.	Within 180 days of the device implant

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
6MHW distance change	6-minute hall walk (6MHW) distance change from baseline to 12 months.	12-months follow-up
Days lost to death or hospitalization		24-months follow-up
NT-proBNP level change	NT-proBNP level change from baseline to 12 months	12-months follow up
Quality of Life (QoL) Score Change	QoL score change from baseline to 12 months, measured by the Minnesota Living With Heart Failure (MLWHF) questionnaire, a 21-question survey that uses a 0-5 scale where a lower score indicates better QoL.	12-months follow-up
All-cause mortality	All-cause mortality rate for all randomized participants through 24-months of follow-up.	24-months follow-up

Collaborators and Investigators

• Sponsor: CVRx, Inc.

Publications and helpful links

Helpful Links

• Sponsor website

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2026
• Primary Completion (Estimated): January 1, 2033
• Study Completion (Estimated): January 1, 2033

Study Registration Dates

• First Submitted: November 14, 2025
• First Submitted That Met QC Criteria: November 14, 2025
• First Posted (Actual): November 18, 2025

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: June 3, 2026
• Last Verified: June 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: 360069-001

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