Endovascular Ablation of the Right Greater Splanchnic Nerve in Subjects With Reduced Ejection Fraction (R-HFrEF)

Endovascular Ablation Of The Right Greater Splanchnic Nerve In Subjects Having Heart Failure With Reduced Ejection Fraction: Randomized Controlled Feasibility Trial

This study is a small, early-stage clinical trial designed to test whether a new catheter-based procedure is safe and may help people with heart failure with reduced ejection fraction (HFrEF). The procedure uses the Satera Ablation System to treat the right greater splanchnic nerve, which may play a role in heart failure symptoms. The study also aims to identify which types of patients might benefit most from this treatment in the future.

Up to 50 patients aged 40 or older with HFrEF will take part at as many as 10 hospitals worldwide. The study is prospective, meaning patients are followed forward in time, and it is randomized, double-blinded, and sham-controlled. Patients are randomly assigned in a 2:1 ratio to either receive the actual nerve ablation treatment or a sham (placebo) procedure. Randomization happens during the procedure, after anesthesia or sedation, to reduce the risk of revealing which treatment the patient receives.

Neither the patient nor their heart failure doctor will know whether the patient received the real treatment or the sham. However, the doctor performing the procedure and certain study staff will know, mainly for safety and operational reasons.

The sham procedure is designed to mimic the real procedure as closely as possible without performing the nerve ablation. It involves placing a small needle in the groin or neck and accessing the vein, but no treatment catheter is inserted. The sham procedure takes about the same amount of time as the real treatment (around 45 minutes) to help account for any placebo effect.

Overall, this study is focused on evaluating safety and early signs of benefit rather than proving long-term effectiveness.

Study Overview

• Status: Not yet recruiting
• Conditions: Heart Failure With Reduced Ejection Fraction (HFrEF)
• Intervention / Treatment: Device: Right Greater Splanchnic Nerve (GSN) ablation; Procedure: Sham Control

• Study Type: Interventional
• Enrollment (Estimated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Judit Adorjan; Phone Number: +1 650 722-1119; Email: j.adorjan@axontherapies.com

Study Locations

• Czechia
  • Prague, Czechia
    • Motol and Homolka University Hospital
• Poland
  • Wroclaw, Poland
    • Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wrocławiu
• Spain
  • Valencia, Spain
    • Hospital Clínico Universitario de Valencia-INCLIVA
  • Valencia, Spain
    • Vithas Valencia Turia
• United Kingdom
  • Leeds, United Kingdom
    • Leeds General Infirmary
  • London, United Kingdom
    • King's College London

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. Chronic heart failure, defined as:

   1. Symptoms of HF requiring current (QD or QOD or appropriate dosing as per screening committee) treatment with loop diuretics for at least 30 days prior to screening visit, AND
   2. NYHA class II, NYHA class III, or ambulatory NYHA class IV symptoms at screening or signs of HF, AND
   3. NT-proBNP >800 pg/ml in normal sinus rhythm (>1400 pg/ml in atrial fibrillation or flutter) within 3 months of consent, with no adjustment for BMI

2. Ongoing stable GDMT HF management for a minimum of 30 days prior to screening (unless unable to tolerate GDMT) which refers to those HF drugs carrying a Class I indication, including:

   1. An inhibitor of the renin-angiotensin system (RAS inhibitor), including an angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) or angiotensin receptor-neprilysin inhibitor (ARNI) and beta-blocker (BB).
   2. A mineralocorticoid receptor antagonist (MRA), Sodium-Glucose Transport 2 inhibitor (SGLT2i), or nitrates/hydralazine, should be used in appropriate patients, according to the published guidelines unless intolerant or not indicated.
   3. Drug intolerance, contraindications, or lack of indications must be attested to by the investigator. Patients should be on appropriate doses of diuretics as required for volume control.
   4. Stable GDMT refers to consistent dose (change is considered a more than 100% increase or 50% decrease in dose) for at least 30 days prior to screening visit or as appropriate per the screening committee.
3. 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.
4. Considered for Class I recommended cardiac rhythm management device therapy. Specifically: if indicated by class I guidelines, cardiac resynchronization therapy (CRT), an implanted cardioverter- defibrillator (ICD) or a pacemaker should be implanted at least 3 months prior to enrollment. These criteria may be waived if a patient is clinically contraindicated for these therapies or refuses them and must be attested to by the investigator.
5. LVEF 20% - 40% (at screening visit and determined by echo core lab).
6. Age ≥40 years.
7. 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 enrollment.

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 or has undergone transplant.
   4. Presence of, or history of, mechanical circulatory support for HF.
   5. Planned other advanced HF Therapies in the next 12 months.
4. Right heart dysfunction defined as tricuspid annular plane systolic excursion (TAPSE) <12 mm or right ventricular (RV) fractional area change (FAC) <25% (at screening visit and determined by echo core lab).
5. Body mass index (BMI) >45 kg/m2.
6. 6-minute walk test distance <100 meters OR >450 meters.
7. Admission for HF within the 30 days prior to planned index procedure.
8. 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.
9. Orthostatic pulse pressure narrowing from supine to standing (+3 minutes) of ≥10mmHg in the absence of a HR increase >15bpm
10. Postural orthostatic tachycardia syndrome or preload insufficiency syndrome or on medical therapy for neurogenic orthostatic hypotension (e.g., midodrine, droxidopa).
11. Systolic BP <100 mmHg or >170 mmHg despite appropriate medical management.
12. Baseline screening ECG resting HR >100 beats per minute or ventricular tachycardia.
13. Catheter ablation for atrial fibrillation within 6 months prior to screening or planned in the next 12 months at the time of screening.

14. 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.
15. Any planned procedure to address valve disease in the past 6 months.
16. Known hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis, or other infiltrative cardiomyopathy (e.g., hemochromatosis, sarcoidosis).
17. History of clinically significant liver cirrhosis.
18. Prior weight loss surgery
19. Dialysis dependent; or estimated GFR <20 ml/min/1.73 m2 by CKD-EPI creatinine equation.
20. Arterial oxygen saturation <90% on room air.
21. 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).
22. Participating in conflicting investigational drug or device study that is not completed within 30 days prior to the screening visit.
23. Life expectancy <12 months for non-cardiovascular reasons.
24. 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.
25. Females who are pregnant or lactating or planning to become pregnant during the next year.
26. LVEDD > 7.5 cm (at screening visit and determined by echo core lab)

27. Estimated peak pulmonary artery pressure (PAP) > 70 mmHg (at screening visit and determined by echo core lab).

    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: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Greater Splanchnic Nerve Ablation; Subjects receive catheter-based unilateral ablation of the right greater splanchnic nerve (GSN) using the Satera Ablation System. Randomization occurs during the procedure after anesthesia or sedation and after confirmation that the subject's vein anatomy is suitable for treatment.	Device: Right Greater Splanchnic Nerve (GSN) ablation; Subjects receive catheter-based unilateral ablation of the right greater splanchnic nerve.
Sham Comparator: Sham treatment; Subjects undergo a simulated procedure designed to mimic the treatment experience without delivering nerve ablation. This includes venous access via a small needle puncture in the groin or neck and assessment of vein anatomy, but no treatment catheter is inserted and no ablation is performed. The sham procedure lasts approximately the same amount of time as the active treatment.	Procedure: Sham Control; Simulated procedure designed to mimic the treatment experience without delivering nerve ablation

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device or procedure related serious adverse events	Evaluation of device or procedure related serious adverse events based on Clinical Events Committee (CEC) assessment	Treatment through the 1 month
NT-proBNP (6 months)	Assessment of change in NT-ProBNP from baseline to 6-month follow up visit	Baseline through the 6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Serious device related cardiac or vascular events	Incidence of serious device related cardiac or vascular events for up to 12 months	Treatment through the 12 months
Device or procedure related pain	Device or procedure related pain lasting at least 30 days and requiring medical management	Enrollment through the 12 months
Orthostatic hypotension	Incidence of new orthostatic hypotension up to 12 months	Procedure through 12 months
Acute Kidney Injury	Incidence of AKI requiring renal replacement therapy up to 12 months	Procedure through 12 months
Worsening Glomerular Filtration Rate (GFR)	Incidence of worsening GFR (defined as change > 50% for at least 30 days in duration) up to 12 months	Procedure through 12 months
Adverse Events	Incidence of all Adverse Events through 12 months	Procedure through 12 months
Mortality	Incidence of all mortality for up to 12 months summarized as all-cause mortality, CV mortality, or heart failure-related	Procedure through 12 months
Left Ventricular End Diastolic Volume (LVEDV)	Change in LVEDV from baseline indexed for body surface area (LVEDVi ml/m2) at 6 and 12 month follow up	Baseline through 6- and 12- months
Left Ventricular Ejection Fraction (LVEF)	Change in LVEF from baseline at 6 and 12 month follow up	Baseline through 6- and 12-months
NT-proBNP (12 months)	Change in NT-proBNP evaluated over time from baseline through 12 months	Baseline through 12 months
Kansas City Cardiomyopathy Questionnaire (KCCQ)	Change in KCCQ scores evaluated over time from baseline through 6 and 12 months	Baseline through 6- and 12-months
6-minute Walk Test (6MWT)	Change in 6MWT evaluated over time from baseline through 6 and 12 months	Baseline through 6- and 12-months
Worsening Heart Failure (Time to)	Time to first heart failure hospitalization or worsening heart failure event through 6 and 12 months	Baseline through 6- and 12-months
Worsening Heart Failure (Incidence)	Incidence of heart failure hospitalization and worsening heart failure events through 6 and 12 months	Baseline through 6- and 12-months
Composite Endpoint	Hierarchical composite endpoint of cardiovascular death, heart failure events, and changes from baseline to 12 months in KCCQ OSS	Baseline through 12 months

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diuretic Dose	Change in diuretic dose through 6 and 12 months	Baseline through 6- and 12 months
High Sensitivity C-reactive Protein	Change in high sensitivity C-reactive protein levels from baseline through 6 and 12 months	Baseline through 6- and 12 months
Weight	Change in weight from baseline through 6 and 12 months	Baseline through 6- and 12 months
HbA1c	Change in HbA1c from baseline through 6 and 12 months	Baseline through 6- and 12 months
Technical Success (Primary) - treatment cohort only	Technical success of RF ablation of the GSN at the T11 level, defined as successful catheter positioning at the target site, completion of RF energy delivery, and absence of device-related Serious Adverse Events.	Procedure
Technical Success (Secondary) - treatment cohort only	Technical success (Secondary) of RF ablation of the GSN at the T10 level, defined as successful catheter positioning at the target site, completion of RF energy delivery, and absence of device-related Serious Adverse Events.	Procedure
SGLT2 Inhibitor Dose	Number of changes in SGLT2 Inhibitor dose and percentage of subjects with at least one change through 6- and 12-months	Baseline through 6- and 12-months
Angiotensin Receptor Blocker (ARB) Dose	Number of changes in Angiotensin Receptor Blocker Dose and percentage of subjects with at least one change though 6- and 12-months	Baseline through 6- and 12-months
ACE Inhibitor Dose	Number of subjects with changes in ACE Inhibitor Dose and percentage of subjects with at least one change through 6- and 12-months	Baseline through 6- and 12-months
Angiotensin Receptor-Neprilysin Inhibitor (ARNI) Dose	Number of subjects with changes in Angiotensin Receptor-Neprilysin Inhibitor dose and percentage of subjects with at least one change through 6- and 12-months	Baseline through 6- and 12-months
Aldosterone Antagonist (MRA) Dose	Number of subjects with changes in Aldosterone Antagonist (MRA) Dose and percentage of subjects with at least one change through 6- and 12-months	Baseline through 6- and 12-months
Beta Blocker Dose	Number of subjects with changes in Beta Blocker dose and percentage of subjects with at least one change through 6- and 12-months	Baseline through 6- and 12-months
Aldosterone (ALD)	Change in aldosterone levels from baseline through 6- and 12-months	Baseline through 6- and 12-months
Renin	Change in Renin levels from Baseline through 6- and 12-months	Baseline through 6- and 12-months

Collaborators and Investigators

• Sponsor: Axon Therapies, Inc.
• Investigators: Principal Investigator: Piotr Ponikowski, MD, PhD, Professor of Cardiology, Head of the Department of Heart Diseases at Wroclaw Medical University; Principal Investigator: Marat Fudim, MD, MHS, Associate Professor of Medicine, Duke Clinical Research Institute of Cardiology; Principal Investigator: Klaus Witte, MD, Senior Lecturer in Cardiology and Consultant Cardiologist Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds and Leeds Teaching Hospitals NHS Trust

Publications and helpful links

General Publications

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• Savarese G, Carrero JJ, Pitt B, Anker SD, Rosano GMC, Dahlstrom U, Lund LH. Factors associated with underuse of mineralocorticoid receptor antagonists in heart failure with reduced ejection fraction: an analysis of 11 215 patients from the Swedish Heart Failure Registry. Eur J Heart Fail. 2018 Sep;20(9):1326-1334. doi: 10.1002/ejhf.1182. Epub 2018 Mar 26.
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Study record dates

Study Major Dates

• Study Start (Estimated): March 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): September 1, 2028

Study Registration Dates

• First Submitted: January 29, 2026
• First Submitted That Met QC Criteria: February 4, 2026
• First Posted (Actual): February 11, 2026

Study Record Updates

• Last Update Posted (Actual): February 11, 2026
• Last Update Submitted That Met QC Criteria: February 4, 2026
• Last Verified: February 1, 2026

More Information

Terms related to this study

• Keywords: Heart Failure; Reduced Ejection Fraction; Right Greater Splanchnic Nerve (GSN)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: CP003

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: Yes