Heart Failure With Reduced Ejection Fraction (HFrEF)
Conditions
Keywords
Heart Failure, Reduced Ejection Fraction, Right Greater Splanchnic Nerve (GSN)
Brief 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). 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.
Interventions
DEVICERight Greater Splanchnic Nerve (GSN) ablation
Subjects receive catheter-based unilateral ablation of the right greater splanchnic nerve.
PROCEDURESham Control
Simulated procedure designed to mimic the treatment experience without delivering nerve ablation
Sponsors
Axon Therapies, Inc.
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Intervention model description
Randomized, sham controlled, double blinded
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
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).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Device or procedure related serious adverse events | 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) | Baseline through the 6 months | Assessment of change in NT-ProBNP from baseline to 6-month follow up visit |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Serious device related cardiac or vascular events | Treatment through the 12 months | Incidence of serious device related cardiac or vascular events for up to 12 months |
| Device or procedure related pain | Enrollment through the 12 months | Device or procedure related pain lasting at least 30 days and requiring medical management |
| Orthostatic hypotension | Procedure through 12 months | Incidence of new orthostatic hypotension up to 12 months |
| Acute Kidney Injury | Procedure through 12 months | Incidence of AKI requiring renal replacement therapy up to 12 months |
| Worsening Glomerular Filtration Rate (GFR) | Procedure through 12 months | Incidence of worsening GFR (defined as change \> 50% for at least 30 days in duration) up to 12 months |
| Adverse Events | Procedure through 12 months | Incidence of all Adverse Events through 12 months |
| Mortality | Procedure through 12 months | Incidence of all mortality for up to 12 months summarized as all-cause mortality, CV mortality, or heart failure-related |
| Left Ventricular End Diastolic Volume (LVEDV) | Baseline through 6- and 12- months | Change in LVEDV from baseline indexed for body surface area (LVEDVi ml/m2) at 6 and 12 month follow up |
| Left Ventricular Ejection Fraction (LVEF) | Baseline through 6- and 12-months | Change in LVEF from baseline at 6 and 12 month follow up |
| NT-proBNP (12 months) | Baseline through 12 months | Change in NT-proBNP evaluated over time from baseline through 12 months |
| Kansas City Cardiomyopathy Questionnaire (KCCQ) | Baseline through 6- and 12-months | Change in KCCQ scores evaluated over time from baseline through 6 and 12 months |
| 6-minute Walk Test (6MWT) | Baseline through 6- and 12-months | Change in 6MWT evaluated over time from baseline through 6 and 12 months |
| Worsening Heart Failure (Time to) | Baseline through 6- and 12-months | Time to first heart failure hospitalization or worsening heart failure event through 6 and 12 months |
| Worsening Heart Failure (Incidence) | Baseline through 6- and 12-months | Incidence of heart failure hospitalization and worsening heart failure events through 6 and 12 months |
| Composite Endpoint | Baseline through 12 months | Hierarchical composite endpoint of cardiovascular death, heart failure events, and changes from baseline to 12 months in KCCQ OSS |
Countries
Czechia, Poland, Spain, United Kingdom
Contacts
CONTACTJudit Adorjan
PRINCIPAL_INVESTIGATORPiotr Ponikowski, MD, PhD
Professor of Cardiology, Head of the Department of Heart Diseases at Wroclaw Medical University
PRINCIPAL_INVESTIGATORMarat Fudim, MD, MHS
Associate Professor of Medicine, Duke Clinical Research Institute of Cardiology
PRINCIPAL_INVESTIGATORKlaus 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
Outcome results
None listed