Endovascular Ablation of the Right Greater Splanchnic Nerve in Subjects Having HFpEF (Rebalance-HF)

Endovascular Ablation of the Right Greater Splanchnic Nerve in Subjects Having Heart Failure With Preserved Ejection Fraction: Randomized Controlled Feasibility Trial - The Rebalance HF Study

The purpose of this clinical study is to evaluate the safety and early effectiveness of a catheter-based procedure that treats a nerve called the right greater splanchnic nerve. The study includes people who have heart failure with preserved ejection fraction (HFpEF). The goal is to learn whether this procedure, performed using the Satera Ablation System, may help improve symptoms and to better understand which patients may benefit most from this treatment in the future.

Study Overview

• Status: Recruiting
• Conditions: Heart Failure With Preserved Ejection Fraction (HFpEF
• Intervention / Treatment: Device: Greater Splanchnic Nerve Ablation; Device: Sham Control

Detailed Description

Up to 150 people will take part in this clinical study.

Phase I of the REBALANCE-HF Study

The first part of the study took place between January 2021 and March 2023. During this phase, 116 patients participated. Researchers reviewed the results to learn whether the procedure appeared safe and whether it might help improve symptoms in people with heart failure with preserved ejection fraction (HFpEF).

This early review showed encouraging results in some patients. It also helped researchers identify a group of patients who seemed more likely to benefit from the procedure.

Phase II of the REBALANCE-HF Study:

The current phase of the study focuses on patients who have similar characteristics to those who responded well in Phase I. The goal is to confirm whether this group of patients may benefit most from the treatment and whether the procedure should be studied further in a larger future trial.

This study will take place at multiple hospitals and research centers.

Participants who qualify for the study will be randomly assigned to one of two groups:

• Treatment group: The procedure is performed using the Satera Ablation System to treat a nerve called the greater splanchnic nerve.
• Control (sham) group: A simulated procedure is performed, but the treatment itself is not delivered.

Participants will be assigned to a group by chance, similar to flipping a coin, although twice as many patients will receive the treatment as the sham procedure (2:1 ratio).

The group assignment will happen during the procedure after anesthesia is given, and only after the doctor confirms that the patient's anatomy is suitable for the procedure.

Blinding:

To make sure the results are fair and unbiased:

• Participants and their heart failure doctors will not know whether the patient received the treatment or the sham procedure.
• The doctor performing the procedure and certain study staff will know which procedure is performed so they can carry out the procedure safely.
• The study safety team will also know this information to help monitor patient safety.

Sham Procedure:

A sham procedure is used to help researchers understand whether any improvements are due to the treatment itself or to the placebo effect.

During the sham procedure:

A small needle puncture is made in the groin or neck, similar to what is done for many heart procedures.

Doctors check the veins to confirm whether the procedure could have been performed.

However, the treatment catheter is not used and the nerve is not treated.

The sham procedure takes about 45 minutes, which is about the same amount of time as the treatment procedure.

Number of Participants:

90 patients were assigned to treatment or sham during Phase I.

In Phase II, up to 60 additional patients will be enrolled.

About 40 patients will receive the treatment, and about 20 will receive the sham procedure.

• Study Type: Interventional
• Enrollment (Estimated): 150
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Judit Adorjan; Phone Number: 16507221119; Email: j.adorjan@axontherapies.com
• Study Contact Backup: Name: Jennifer Moore, MS; Email: jennifer@axontherapies.com

Study Locations

• United States
  • Alabama
    • Birmingham, Alabama, United States, 35211
      • Completed
      • Cardiology PC
  • Arizona
    • Phoenix, Arizona, United States, 85016
      • Active, not recruiting
      • Arizona Cardiovascular Research Center
  • California
    • La Jolla, California, United States, 92037
      • Active, not recruiting
      • Scripps Health
    • San Francisco, California, United States, 94143
      • Recruiting
      • University of California, San Francisco
      • Principal Investigator: Liviu Klein, MD
      • Contact: Priscilla Zhang; Phone Number: 415-514-7903; Email: Priscilla.Zhang@ucsf.edu
  • Illinois
    • Chicago, Illinois, United States, 60637
      • Recruiting
      • University of Chicago Medical Center
      • Contact: Adaeze Emeka; Email: adaeze.emeka@bsd.uchicago.edu
      • Principal Investigator: Mark Nathan Belkin, MD
    • Chicago, Illinois, United States, 60611
      • Recruiting
      • Bluhm Cardiovascular Institute of Northwestern University
      • Principal Investigator: Ravi Patel, MD
      • Contact: Daniel Roshevsky; Email: droshevs@nm.org
    • Springfield, Illinois, United States, 62701
      • Active, not recruiting
      • Prairie Education and Research Cooperative
  • Indiana
    • Indianapolis, Indiana, United States, 46260
      • Completed
      • Ascension St. Vincent - Cardiovascular Research Institute
  • Louisiana
    • Houma, Louisiana, United States, 70360
      • Recruiting
      • Cardiovascular Institute of the South
      • Principal Investigator: Peter Fail, MD
      • Contact: Kimberly Lirette; Email: kimberly.lirette@cardio.com
  • Michigan
    • Ann Arbor, Michigan, United States, 48109
      • Recruiting
      • Michigan Medicine, University of Michigan
      • Principal Investigator: Scott Hummel, MD
  • Minnesota
    • Rochester, Minnesota, United States, 55905
      • Recruiting
      • Mayo Clinic
      • Principal Investigator: Barry Borlaug, MD
      • Contact: Alyssa Ploof; Email: ploof.alyssa@mayo.edu
  • Missouri
    • St Louis, Missouri, United States, 63136
      • Recruiting
      • St. Louis Heart and Vascular
      • Principal Investigator: Gil Vardi, MD
      • Contact: Melissa McCann; Email: mmccann@slhv.com
  • New York
    • New York, New York, United States, 10021
      • Recruiting
      • Weill Cornell Medicine
      • Contact: Caroline Goldstein; Email: cag4020@med.cornell.edu
      • Principal Investigator: Parag Goyal, MD
    • New York, New York, United States, 10032
      • Recruiting
      • Columbia University Medical Center
      • Principal Investigator: Nir Uriel, MD
    • New York, New York, United States, 10029
      • Active, not recruiting
      • ICAHN School of Medicine at Mount Sinai
    • Rochester, New York, United States, 14621
      • Recruiting
      • Rochester General Hospital
      • Contact: Kathleen Ebeling, RN; Email: kathleen.ebeling@rochesterregional.org
      • Principal Investigator: Scott Feitell, DO
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Recruiting
      • Duke University Medical Center
      • Principal Investigator: Marat Fudim, MD, MHS
      • Contact: Matthew Gray; Email: james.gray@duke.edu
  • Ohio
    • Columbus, Ohio, United States, 43210
      • Recruiting
      • Ohio State University Wexner Medical Center
      • Contact: Kalyn Ferguson; Email: kalyn.ferguson@osumc.edu
      • Principal Investigator: Alexandria Miller, MD
  • South Carolina
    • Charleston, South Carolina, United States, 29425
      • Recruiting
      • Medical University of South Carolina
      • Principal Investigator: Sheldon Litwin, MD
      • Contact: Elly Borhanian; Email: borhania@musc.edu
  • Virginia
    • Richmond, Virginia, United States, 23298
      • Active, not recruiting
      • Virginia Commonwealth University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 36 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria

1. Chronic heart failure, defined as:

   1. Symptoms of HF requiring current (intermittent or continuous) treatment with diuretics for >30 days, AND
   2. NYHA class II with a history of >NYHA class II in the past year, NYHA class III, or ambulatory NYHA class IV symptoms (paroxysmal nocturnal dyspnea, orthopnea, dyspnea on mild or moderate exertion) at screening or signs of HF (any rales post cough, chest x-ray demonstrating pulmonary congestion), AND
   3. At least one of the following:

   i. ≥1 HF hospital admission (with HF as the primary diagnosis) including treatment with intravenous (IV) diuretics or urgent unplanned treatment with IV diuretics in healthcare facility within past 12 months, OR ii. NT-proBNP >300 pg/ml in normal sinus rhythm (>450 pg/ml in atrial fibrillation or flutter) within the past 6 months; BNP >100 pg/ml in normal sinus rhythm (>300 pg/ml in atrial fibrillation or flutter) within the past 6 months, OR iii. Right heart catheterization (RHC) with PCWP ≥ with PCWP ≥18 mmHg at rest or 25 mmHg during exercise at the time of the screening RHC.

2. Ongoing stable GDMT HF management (unless unable to tolerate GDMT) and management of potential comorbidities according to the 2022 ACCF/AHA Guideline for the Management of Heart Failure (Class 1 and 2a recommendations), with no significant changes [≥100% increase or ≥50% decrease] for a minimum of 1 month (30 days) prior to screening, that is expected to be maintained without change for at least 6 months. Participants cannot have started a glucagon-like peptide (GLP)-1 or gastric inhibitory peptide (GIP) agonist within the last 6 months or plan to start a GLP-1 or GIP agonist within the ensuing 6 months after enrollment.
3. LVEF ≥50% (site-determined by transthoracic echocardiography) within the past 6 months.
4. Age ≥40 years.
5. Subject is willing and able to provide appropriate study-specific informed consent, follow protocol procedures, and comply with follow-up visit requirements.

Exclusion Criteria:

1. MI (type I) and/or percutaneous cardiac intervention within 3 months prior to screening; CABG in past 3 months prior to screening, or current indication for coronary revascularization.
2. Cardiac resynchronization therapy initiated within 3 months prior to screening.

3. Advanced heart failure defined as one or more of the following:

   1. ACC/AHA/ESC Stage D HF or non-ambulatory NYHA Class IV HF.
   2. Inotropic infusion (continuous or intermittent) within 6 months prior to screening.
   3. Subject is on the cardiac transplant waiting list.
   4. Presence of or prior history of mechanical circulatory support for HF.
4. Poor left heart compliance as determined by pulse-wave Doppler transmitral early-to-late (E/A) ratio >2.0 assessed by the screening echocardiogram. The Screening Committee will evaluate left heart function if the transmitral A velocity is not measurable or absent.
5. Right heart dysfunction defined as tricuspid annular plane systolic excursion (TAPSE) <12 mm or right ventricular (RV) fractional area change (FAC) <25% assessed by the screening echocardiogram.
6. Body mass index (BMI) >45 kg/m2.
7. 6-minute walk test distance <100 meters OR >450 meters.
8. Admission for HF within the 30 days prior to planned index procedure.
9. Any known history of orthostatic hypotension or orthostatic hypotension at the time of screening (regardless of the presence of symptoms). Orthostatic hypotension is defined as a systolic blood pressure (BP) decrease of >20 mmHg upon going from supine to standing position or undergoing treatment with Midodrine.
10. Orthostatic pulse pressure change from supine to standing decrease of >10mmHg in the absence of a HR increase >15bpm
11. Postural orthostatic tachycardia syndrome or preload insufficiency syndrome.
12. Systolic BP <100 mmHg or >170 mmHg despite appropriate medical management.
13. Baseline screening ECG resting HR >100 beats per minute or ventricular tachycardia.
14. Catheter ablation for atrial fibrillation within 6 months prior to screening or planned in the next 12 months at the time of screening.
15. Left ventricular EF <40% within the 3 years prior to screening unless reduced EF was transient and associated with an acute event.

16. Presence of significant valve disease defined by the site cardiologist as:

    1. Greater than mild mitral valve stenosis.
    2. Greater than moderate mitral valve regurgitation.
    3. Greater than moderate-to-severe tricuspid valve regurgitation.
    4. Greater than moderate aortic valve stenosis or regurgitation.
17. Known hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis, or other infiltrative cardiomyopathy (e.g., hemochromatosis, sarcoidosis).
18. History of clinically significant liver cirrhosis.
19. Prior weight loss surgery
20. Dialysis dependent; or estimated GFR <25 ml/min/1.73 m2 by CKD-EPI creatinine equation.
21. Arterial oxygen saturation <90% on room air.
22. Chronic pulmonary disease requiring continuous home oxygen OR hospitalization for exacerbation of chronic pulmonary disease (including intubation) in the 12 months before study entry OR known history of GOLD Class III or worse chronic obstructive pulmonary disease (COPD).
23. Participating in conflicting investigational drug or device study that is not completed within 30 days prior to the screening visit.
24. Life expectancy <12 months for non-cardiovascular reasons.
25. Any condition, or history of illness or surgery that, in the opinion of the site investigator or Screening Committee, might confound the results of the study or pose additional risks to the patient.
26. Females who are pregnant or lactating or planning to become pregnant during the next year.

27. Any of the following measured by screening right heart catheterization:

    1. Mean right atrial pressure (RAP) >20 mmHg at rest
    2. Cardiac index <2.0 L/min/m2 at rest
    3. Pulmonary vascular resistance (PVR) >4 Wood units

    Exclusion Criteria Assessed During the index procedure:

28. Vessel tortuosity or variant vascular anatomy that could preclude the access or maneuvering of the interventional device from the access site to target vessel. This includes previous spine surgery that may impact the ability to access and treat the target sites of T11 and T10.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Greater Splanchnic Nerve Ablation; After anesthesia is given, doctors will use the Satera Ablation System to reach a nerve called the right greater splanchnic nerve. Subjects receive catheter-based unilateral ablation of the right greater splanchnic nerve.	Device: Greater Splanchnic Nerve Ablation; The greater splanchnic nerve (GSN) ablation procedure begins with a small needle puncture in the groin or neck to access a vein, using methods that are commonly used for heart procedures. Doctors then guide thin tubes and wires through the vein to reach a nerve called the right greater splanchnic nerve. X-ray imaging is used to help the doctor see where the catheter is and guide it to the correct location. Once the catheter is in the right place, the doctor uses the device to treat the nerve using controlled heat.
Sham Comparator: Sham Control Arm; After anesthesia is given, doctors will place a small tube into a vein. The steps and length of the procedure will be similar to the Axon treatment procedure, but the study treatment will not be performed.	Device: Sham Control; During the sham procedure, a small needle puncture will be made in the groin or neck to access a vein using standard medical techniques. A short tube will be placed into the vein, similar to what is done for many heart procedures. The Satera catheter and treatment devices will not be inserted, and the nerve will not be treated. The procedure will take about the same amount of time as the treatment procedure.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Primary Safety Endpoint: Device or procedure related serious adverse events	Evaluation of device or procedure-related serious adverse events at 1-month follow-up based on Clinical Events Committee (CEC) assessment	1 Month
Primary Efficacy Endpoint: KCCQ (6 months)	Assessment of change in Kansas City Cardiomyopathy Questionnaire (KCCQ) from baseline to 6-month follow up visit	Baseline through 6-months
Primary Efficacy Endpoint: 6MWT (6 months)	Assessment of change in Six Minute Walk Test (6MWT) from baseline to the 6-month follow up visit	Baseline through 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pulmonary Capillary Wedge Pressure (PCWP)	Change in pulmonary capillary wedge pressure (PCWP) at resting, legs up, 20 Watts, and Peak Exercise Stage from Baseline to the 1-month follow up visit	Baseline through 1-month
Stress blood volume	Change in estimated stress blood volume at resting, legs up, 20Watts, and Peak Exercise Stage from Baseline to the 1-month follow up visit.	Baseline through 1-month
NT-proBNP	Change in NT-proBNP levels from Baseline through the 24-month visit	Baseline through 24-months
KCCQ (24-months)	Change in KCCQ scores from baseline through the 24-month visit	Baseline through 24-months
6MWT (24-months)	Change in 6MWT from Baseline through the 24-month visit	Baseline through 24-months
Time to first heart failure event	Time to first heart failure event (hospitalizations and worsening heart failure events) through the 24-month visit	Treatment through 24-months
Incidence of heart failure events	Incidence of heart failure events (hospitalizations and worsening heart failure events) through the 24-month visit	Treatment through 24-months
Hierarchical composite endpoint (12-months)	Composite endpoint of cardiovascular death, heart failure events, and changes in KCCQ from Baseline to the 12-month visit	Baseline through 12-months
Incidence of serious device related cardiac or vascular events	Assessment of the incidence of serious device related cardiac or vascular events through 12- and 24-months	Treatment through 12- and 24-months
Device or procedure related pain	Assessment of device or procedure related pain lasting at least 30 days and requiring medical management	Treatment through 24-months
Orthostatic hypotension	Incidence of new orthostatic hypotension up to 12- and 24-months	Treatment through 12- and 24-months
Acute Kidney Injury (AKI)	Incidence of AKI requiring renal replacement therapy up to 12- and 24-months	Baseline through 12-and 24-months
Glomerular Filtration Rate (GFR)	Incidence of worsening GFR (defined as >50% for at least 30 days in duration) up to 12- and 24-months	Baseline through 12- and 24-months
Adverse Events	Incidence of all Adverse Events through 12- and 24-months	Procedure through 12- and 24-months
Mortality	Incidence of all mortality for up to 6-, 12-, and 24-months summarized as all-cause mortality, CV mortality, or heart failure-related	Procedure through 6-, 12- and 24-months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Exploratory endpoint: Heart failure related medication changes (24-months)	Freedom from heart failure related medication changes through the 24-month visit	Baseline through 24-months
Exploratory Endpoint: Diuretic medication (24-months)	Change in diuretic dose through the 24-month visit	Baseline through 24-months
Exploratory Endpoint: Diastolic function (24-months)	Assessment of diastolic function by transthoracic echocardiography evaluated over time from baseline through 24-months	Baseline through 24-months
Exploratory Endpoint: C-reactive protein	Change in c-reactive protein levels from Baseline through 24-months	Baseline through 24-months
Exploratory Endpoint: Aldosterone (ALD)	Change in aldosterone levels from Baseline through 24-months	Baseline through 24-months
Exploratory Endpoint: Renin	Change in Renin levels from Baseline through 24-months	Baseline through 24-months
Exploratory Endpoint: Weight	Change in weight from Baseline through 24-months	Baseline through 24-months

Collaborators and Investigators

• Sponsor: Axon Therapies, Inc.
• Collaborators: NAMSA; Northwestern University Feinberg School of Medicine; Cardiovascular Research Foundation, New York
• Investigators: Principal Investigator: Sanjiv S Shah, MD, Northwestern University

Publications and helpful links

General Publications

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Study record dates

Study Major Dates

• Study Start (Actual): December 18, 2020
• Primary Completion (Estimated): January 10, 2028
• Study Completion (Estimated): August 10, 2029

Study Registration Dates

• First Submitted: October 7, 2020
• First Submitted That Met QC Criteria: October 13, 2020
• First Posted (Actual): October 19, 2020

Study Record Updates

• Last Update Posted (Actual): March 13, 2026
• Last Update Submitted That Met QC Criteria: March 10, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: HFpEF; Heart Failure with Preserved Ejection Fraction (HFpEF); Greater Splanchnic Nerve; GSN
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure
• Other Study ID Numbers: 09868

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