Heart Failure With Reduced Ejection Fraction (HFrEF)R-HFrEFNCT07403058
Endovascular Ablation of the Right Greater Splanchnic Nerve in Subjects With Reduced Ejection Fraction
A study testing Right Greater Splanchnic Nerve (GSN) ablation in people with Heart Failure With Reduced Ejection Fraction (HFrEF), run by Axon Therapies, Inc. at 9 sites in 5 countries.
Trial summary
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). Read more about this study
- Who is it for?
- Ages 40 years and older
- Conditions the study is for
- Heart Failure With Reduced Ejection Fraction (HFrEF)
- What is being tested?
- Right Greater Splanchnic Nerve (GSN) ablation
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 50 participants
- Where
- 9 sitesin 5 countries
- Study dates
- 12 Jun 2026to 1 Sep 2028
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 40 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Chronic heart failure, defined as:
- 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
- NYHA class II, NYHA class III, or ambulatory NYHA class IV symptoms at screening or signs of HF, AND
- 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
- 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:
- 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).
Show all 14Show fewer
- 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.
- 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.
- 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.
- 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.
- 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.
- LVEF 20% - 40% (at screening visit and determined by echo core lab).
- Age ≥40 years.
- Subject is willing and able to provide appropriate study-specific informed consent, follow protocol procedures, and comply with follow-up visit requirements.
Who cannot join
- 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.
- Cardiac resynchronization therapy initiated within 3 months prior to enrollment.
- Advanced heart failure defined as one or more of the following:
- ACC/AHA/ESC Stage D HF or non-ambulatory NYHA Class IV HF.
- Inotropic infusion (continuous or intermittent) within 6 months prior to screening.
- Subject is on the cardiac transplant waiting list or has undergone transplant.
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- Presence of, or history of, mechanical circulatory support for HF.
- Planned other advanced HF Therapies in the next 12 months.
- 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).
- Body mass index (BMI) >45 kg/m2.
- 6-minute walk test distance <100 meters OR >450 meters.
- Admission for HF within the 30 days prior to planned index procedure.
- 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.
- Orthostatic pulse pressure narrowing from supine to standing (+3 minutes) of ≥10mmHg in the absence of a HR increase >15bpm
- Postural orthostatic tachycardia syndrome or preload insufficiency syndrome or on medical therapy for neurogenic orthostatic hypotension (e.g., midodrine, droxidopa).
- Systolic BP <100 mmHg or >170 mmHg despite appropriate medical management.
- Baseline screening ECG resting HR >100 beats per minute or ventricular tachycardia.
- Catheter ablation for atrial fibrillation within 6 months prior to screening or planned in the next 12 months at the time of screening.
- Presence of significant valve disease defined by the site cardiologist as:
- Greater than mild mitral valve stenosis.
- Greater than moderate mitral valve regurgitation.
- Greater than moderate-to-severe tricuspid valve regurgitation.
- Greater than moderate aortic valve stenosis or regurgitation.
- Any planned procedure to address valve disease in the past 6 months.
- Known hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis, or other infiltrative cardiomyopathy (e.g., hemochromatosis, sarcoidosis).
- History of clinically significant liver cirrhosis.
- Prior weight loss surgery
- Dialysis dependent; or estimated GFR <20 ml/min/1.73 m2 by CKD-EPI creatinine equation.
- Arterial oxygen saturation <90% on room air.
- 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).
- Participating in conflicting investigational drug or device study that is not completed within 30 days prior to the screening visit.
- Life expectancy <12 months for non-cardiovascular reasons.
- 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.
- Females who are pregnant or lactating or planning to become pregnant during the next year.
- LVEDD > 7.5 cm (at screening visit and determined by echo core lab)
- Estimated peak pulmonary artery pressure (PAP) > 70 mmHg (at screening visit and determined by echo core lab).
- 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.
Trial locations and contacts
9 sites in 5 countries. Contact the study team or a site near you to ask about taking part.
9 sites in 5 countries
Spain3 sites, 3 recruiting
- Recruiting
Hospital Universitari Quirónsalud Barcelona
Barcelona
- Recruiting
Hospital Clínico Universitario de Valencia-INCLIVA
Valencia
- Recruiting
Vithas Valencia Turia
Valencia
Georgia2 sites, 2 recruiting
- Recruiting
Heart and Vascular Clinic
Tbilisi
- Recruiting
Tbilisi Heart Center
Tbilisi
United Kingdom2 sites, 2 recruiting
- Not yet recruiting
Leeds General Infirmary
Leeds
- Recruiting
King's College London
London
Czechia1 site, 1 recruiting
- Recruiting
Motol and Homolka University Hospital
Prague
Poland1 site, 1 recruiting
- Not yet recruiting
Uniwersytecki Szpital Kliniczny im. Jana Mikulicza Radeckiego we Wrocławiu
Wroclaw
About this study
Official title: 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.
Read more
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.
- Being tested
- Right Greater Splanchnic Nerve (GSN) ablation, Sham Control
- Keywords
- Heart Failure, Reduced Ejection Fraction, Right Greater Splanchnic Nerve (GSN)
- Medical subject headings
- Heart Failure
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Right Greater Splanchnic Nerve (GSN) ablationDevice
Subjects receive catheter-based unilateral ablation of the right greater splanchnic nerve.
Sham ControlProcedure or surgery
Simulated procedure designed to mimic the treatment experience without delivering nerve ablation
| Study group | Role | What they receive |
|---|---|---|
| Greater Splanchnic Nerve Ablation | Experimental | 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. Receives: Device: Right Greater Splanchnic Nerve (GSN) ablation |
| Sham treatment | Sham comparator | 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. Receives: Procedure: Sham Control |
What is being measured
The primary outcome is the main question the study is designed to answer.
Device or procedure related serious adverse events
Evaluation of device or procedure related serious adverse events based on Clinical Events Committee (CEC) assessment
Measured: Treatment through the 1 month
NT-proBNP (6 months)
Assessment of change in NT-ProBNP from baseline to 6-month follow up visit
Measured: Baseline through the 6 months
Secondary outcomes (15)
Serious device related cardiac or vascular events
Incidence of serious device related cardiac or vascular events for up to 12 months
Measured: Treatment through the 12 months
Device or procedure related pain
Device or procedure related pain lasting at least 30 days and requiring medical management
Measured: Enrollment through the 12 months
Orthostatic hypotension
Incidence of new orthostatic hypotension up to 12 months
Measured: Procedure through 12 months
Acute Kidney Injury
Incidence of AKI requiring renal replacement therapy up to 12 months
Measured: 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
Measured: Procedure through 12 months
Adverse Events
Incidence of all Adverse Events through 12 months
Measured: 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
Measured: 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
Measured: Baseline through 6- and 12- months
Left Ventricular Ejection Fraction (LVEF)
Change in LVEF from baseline at 6 and 12 month follow up
Measured: Baseline through 6- and 12-months
NT-proBNP (12 months)
Change in NT-proBNP evaluated over time from baseline through 12 months
Measured: Baseline through 12 months
Kansas City Cardiomyopathy Questionnaire (KCCQ)
Change in KCCQ scores evaluated over time from baseline through 6 and 12 months
Measured: Baseline through 6- and 12-months
6-minute Walk Test (6MWT)
Change in 6MWT evaluated over time from baseline through 6 and 12 months
Measured: 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
Measured: 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
Measured: 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
Measured: Baseline through 12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2026
- Study start12 Jun 2026
- Primary completion1 Mar 2028 (estimated)
- Study completion1 Sep 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (44)Papers the sponsor has linked to this study.
- Other trials for Heart Failure With Reduced Ejection Fraction (HFrEF)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Randomized, sham controlled, double blinded
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Axon Therapies, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Piotr Ponikowski, MD, PhD, Principal investigator, Professor of Cardiology, Head of the Department of Heart Diseases at Wroclaw Medical UniversityMarat Fudim, MD, MHS, Principal investigator, Associate Professor of Medicine, Duke Clinical Research Institute of CardiologyKlaus Witte, MD, Principal investigator, Senior Lecturer in Cardiology and Consultant Cardiologist Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds and Leeds Teaching Hospitals NHS Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07403058
- Sponsor's protocol ID
- CP003
- Acronym
- R-HFrEF
- Status last verified
- Nov 2026
- First submitted
- 29 Jan 2026
- Last updated
- 6 Nov 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- Undecided
Publications
Finkelstein DM, Schoenfeld DA. Combining mortality and longitudinal measures in clinical trials. Stat Med. 1999 Jun 15;18(11):1341-54. doi: 10.1002/(sici)1097-0258(19990615)18:113.0.co;2-7.
PubMed 10399200Pocock SJ, Ariti CA, Collier TJ, Wang D. The win ratio: a new approach to the analysis of composite endpoints in clinical trials based on clinical priorities. Eur Heart J. 2012 Jan;33(2):176-82. doi: 10.1093/eurheartj/ehr352. Epub 2011 Sep 6.
PubMed 21900289Fudim M, Fail PS, Litwin SE, Shaburishvili T, Goyal P, Hummel SL, Borlaug BA, Mohan RC, Patel RB, Mitter SS, Klein L, Rocha-Singh K, Patel MR, Reddy VY, Burkhoff D, Shah SJ. Endovascular ablation of the right greater splanchnic nerve in heart failure with preserved ejection fraction: early results of the REBALANCE-HF trial roll-in cohort. Eur J Heart Fail. 2022 Aug;24(8):1410-1414. doi: 10.1002/ejhf.2559. Epub 2022 May 29.
PubMed 35598154Fudim M, Patel MR, Boortz-Marx R, Borlaug BA, DeVore AD, Ganesh A, Green CL, Lopes RD, Mentz RJ, Patel CB, Rogers JG, Felker GM, Hernandez AF, Sunagawa K, Burkhoff D. Splanchnic Nerve Block Mediated Changes in Stressed Blood Volume in Heart Failure. JACC Heart Fail. 2021 Apr;9(4):293-300. doi: 10.1016/j.jchf.2020.12.006. Epub 2021 Mar 10.
PubMed 33714749Malek F, Gajewski P, Zymlinski R, Janczak D, Chabowski M, Fudim M, Martinca T, Neuzil P, Biegus J, Mates M, Kruger A, Skalsky I, Bapna A, Engelman ZJ, Ponikowski PP. Surgical ablation of the right greater splanchnic nerve for the treatment of heart failure with preserved ejection fraction: first-in-human clinical trial. Eur J Heart Fail. 2021 Jul;23(7):1134-1143. doi: 10.1002/ejhf.2209. Epub 2021 Jul 16.
PubMed 33932262Maher JW, Johlin FC, Pearson D. Thoracoscopic splanchnicectomy for chronic pancreatitis pain. Surgery. 1996 Oct;120(4):603-9; discussion 609-10. doi: 10.1016/s0039-6060(96)80006-7.
PubMed 8862367Fudim M, Boortz-Marx RL, Ganesh A, DeVore AD, Patel CB, Rogers JG, Coburn A, Johnson I, Paul A, Coyne BJ, Rao SV, Gutierrez JA, Kiefer TL, Kong DF, Green CL, Jones WS, Felker GM, Hernandez AF, Patel MR. Splanchnic Nerve Block for Chronic Heart Failure. JACC Heart Fail. 2020 Sep;8(9):742-752. doi: 10.1016/j.jchf.2020.04.010. Epub 2020 Jun 10.
PubMed 32535123Fudim M, Jones WS, Boortz-Marx RL, Ganesh A, Green CL, Hernandez AF, Patel MR. Splanchnic Nerve Block for Acute Heart Failure. Circulation. 2018 Aug 28;138(9):951-953. doi: 10.1161/CIRCULATIONAHA.118.035260. No abstract available.
PubMed 29804067Baghdadi S, Abbas MH, Albouz F, Ammori BJ. Systematic review of the role of thoracoscopic splanchnicectomy in palliating the pain of patients with chronic pancreatitis. Surg Endosc. 2008 Mar;22(3):580-8. doi: 10.1007/s00464-007-9730-x. Epub 2007 Dec 28.
PubMed 18163168RAPAPORT E, WEISBART MH, LEVINE M. The splanchnic blood volume in congestive heart failure. Circulation. 1958 Oct;18(4 Part 1):581-7. doi: 10.1161/01.cir.18.4.581. No abstract available.
PubMed 13573575Borlaug BA, Nishimura RA, Sorajja P, Lam CS, Redfield MM. Exercise hemodynamics enhance diagnosis of early heart failure with preserved ejection fraction. Circ Heart Fail. 2010 Sep;3(5):588-95. doi: 10.1161/CIRCHEARTFAILURE.109.930701. Epub 2010 Jun 11.
PubMed 20543134Burkhoff D, Tyberg JV. Why does pulmonary venous pressure rise after onset of LV dysfunction: a theoretical analysis. Am J Physiol. 1993 Nov;265(5 Pt 2):H1819-28. doi: 10.1152/ajpheart.1993.265.5.H1819.
PubMed 8238596Funakoshi K, Hosokawa K, Kishi T, Ide T, Sunagawa K. Striking volume intolerance is induced by mimicking arterial baroreflex failure in normal left ventricular function. J Card Fail. 2014 Jan;20(1):53-9. doi: 10.1016/j.cardfail.2013.11.007. Epub 2013 Nov 28.
PubMed 24291683Barnes RJ, Bower EA, Rink TJ. Haemodynamic responses to stimulation of the splanchnic and cardiac sympathetic nerves in the anaesthetized cat. J Physiol. 1986 Sep;378:417-36. doi: 10.1113/jphysiol.1986.sp016228.
PubMed 3795110Fudim M, Ganesh A, Green C, Jones WS, Blazing MA, DeVore AD, Felker GM, Kiefer TL, Kong DF, Boortz-Marx RL, Hernandez AF, Patel MR. Splanchnic nerve block for decompensated chronic heart failure: splanchnic-HF. Eur Heart J. 2018 Dec 21;39(48):4255-4256. doi: 10.1093/eurheartj/ehy682. No abstract available.
PubMed 30346508
Study at a glance
From the registry record, last updated by the sponsor on 6 Nov 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Endovascular Ablation Of The Right Greater Splanchnic Nerve In Subjects Having Heart Failure With Reduced Ejection Fraction: Randomized Controlled Feasibility Trial
- ClinicalTrials.gov ID
- NCT07403058
- Acronym / sponsor ID
- R-HFrEF / CP003
- Keywords
- Heart Failure, Reduced Ejection Fraction, Right Greater Splanchnic Nerve (GSN)
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Axon Therapies, Inc.Industry (pharma, biotech, devices)
- Study start
- 12 Jun 2026 (actual)
- Primary completion
- 1 Mar 2028 (estimated)
- Study completion
- 1 Sep 2028 (estimated)
- First posted
- 11 Feb 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 2
- Model description
- Randomized, sham controlled, double blinded
| Arm | Type | Receives |
|---|---|---|
| Greater Splanchnic Nerve Ablation | Experimental | Device: Right Greater Splanchnic Nerve (GSN) ablationSubjects 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. |
| Sham treatment | Sham comparator | Procedure: Sham ControlSubjects 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. |
Who may qualify
- Ages
- 40 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Chronic heart failure, defined as:
- 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:
- 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.
- 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.
- LVEF 20% - 40% (at screening visit and determined by echo core lab).
Key exclusion criteria (37 listed)
- 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.
- Cardiac resynchronization therapy initiated within 3 months prior to enrollment.
- Advanced heart failure defined as one or more of the following:
- 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).
- Body mass index (BMI) >45 kg/m2.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Right Greater Splanchnic Nerve (GSN) ablationSubjects receive catheter-based unilateral ablation of the right greater splanchnic nerve. | Device | Greater Splanchnic Nerve Ablation |
| Sham ControlSimulated procedure designed to mimic the treatment experience without delivering nerve ablation | Procedure or surgery | Sham treatment |
Primary outcome
Device or procedure related serious adverse events
Time frame: Treatment through the 1 month
Evaluation of device or procedure related serious adverse events based on Clinical Events Committee (CEC) assessment
NT-proBNP (6 months)
Time frame: Baseline through the 6 months
Assessment of change in NT-ProBNP from baseline to 6-month follow up visit
15 secondary outcomes
Serious device related cardiac or vascular events
Time frame: Treatment through the 12 months
Device or procedure related pain
Time frame: Enrollment through the 12 months
Orthostatic hypotension
Time frame: Procedure through 12 months
Acute Kidney Injury
Time frame: Procedure through 12 months
Worsening Glomerular Filtration Rate (GFR)
Time frame: Procedure through 12 months
Adverse Events
Time frame: Procedure through 12 months
Mortality
Time frame: Procedure through 12 months
Left Ventricular End Diastolic Volume (LVEDV)
Time frame: Baseline through 6- and 12- months
Left Ventricular Ejection Fraction (LVEF)
Time frame: Baseline through 6- and 12-months
NT-proBNP (12 months)
Time frame: Baseline through 12 months
Kansas City Cardiomyopathy Questionnaire (KCCQ)
Time frame: Baseline through 6- and 12-months
6-minute Walk Test (6MWT)
Time frame: Baseline through 6- and 12-months
Worsening Heart Failure (Time to)
Time frame: Baseline through 6- and 12-months
Worsening Heart Failure (Incidence)
Time frame: Baseline through 6- and 12-months
Composite Endpoint
Time frame: Baseline through 12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Nov 2026.
- Background: PubMed 10399200Finkelstein DM, Schoenfeld DA. Combining mortality and longitudinal measures in clinical trials. Stat Med. 1999 Jun 15;18(11):1341-54. doi: 10.1002/(sici)1097-0258(19990615)18:113.0.co;2-7.
- Background: PubMed 21900289Pocock SJ, Ariti CA, Collier TJ, Wang D. The win ratio: a new approach to the analysis of composite endpoints in clinical trials based on clinical priorities. Eur Heart J. 2012 Jan;33(2):176-82. doi: 10.1093/eurheartj/ehr352. Epub 2011 Sep 6.
- Background: PubMed 35598154Fudim M, Fail PS, Litwin SE, Shaburishvili T, Goyal P, Hummel SL, Borlaug BA, Mohan RC, Patel RB, Mitter SS, Klein L, Rocha-Singh K, Patel MR, Reddy VY, Burkhoff D, Shah SJ. Endovascular ablation of the right greater splanchnic nerve in heart failure with preserved ejection fraction: early results of the REBALANCE-HF trial roll-in cohort. Eur J Heart Fail. 2022 Aug;24(8):1410-1414. doi: 10.1002/ejhf.2559. Epub 2022 May 29.
- Background: PubMed 33714749Fudim M, Patel MR, Boortz-Marx R, Borlaug BA, DeVore AD, Ganesh A, Green CL, Lopes RD, Mentz RJ, Patel CB, Rogers JG, Felker GM, Hernandez AF, Sunagawa K, Burkhoff D. Splanchnic Nerve Block Mediated Changes in Stressed Blood Volume in Heart Failure. JACC Heart Fail. 2021 Apr;9(4):293-300. doi: 10.1016/j.jchf.2020.12.006. Epub 2021 Mar 10.
- Background: PubMed 33932262Malek F, Gajewski P, Zymlinski R, Janczak D, Chabowski M, Fudim M, Martinca T, Neuzil P, Biegus J, Mates M, Kruger A, Skalsky I, Bapna A, Engelman ZJ, Ponikowski PP. Surgical ablation of the right greater splanchnic nerve for the treatment of heart failure with preserved ejection fraction: first-in-human clinical trial. Eur J Heart Fail. 2021 Jul;23(7):1134-1143. doi: 10.1002/ejhf.2209. Epub 2021 Jul 16.
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- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Piotr Ponikowski, MD, PhD principal investigator
Professor of Cardiology, Head of the Department of Heart Diseases at Wroclaw Medical University
Marat Fudim, MD, MHS principal investigator
Associate Professor of Medicine, Duke Clinical Research Institute of Cardiology
Klaus Witte, MD principal investigator
Senior Lecturer in Cardiology and Consultant Cardiologist Leeds Institute of Cardiovascular and Metabolic Medicine University of Leeds and Leeds Teaching Hospitals NHS Trust
9 sites in 5 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Right Greater Splanchnic Nerve (GSN) ablation in people with Heart Failure With Reduced Ejection Fraction (HFrEF), run by Axon Therapies, Inc. at 9 sites in 5 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 37 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 6 Nov 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 sites in Spain, Georgia, United Kingdom, Czechia, Poland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Judit Adorjan (+1 650 722-1119, j.adorjan@axontherapies.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Device or procedure related serious adverse events (time frame: Treatment through the 1 month). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT07403058, which also lists 44 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Nov 2026.