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
Overview
- Phase
- N/A
- Intervention
- Greater Splanchnic Nerve Ablation
- Conditions
- Not specified
- Sponsor
- Axon Therapies, Inc.
- Enrollment
- 150
- Locations
- 20
- Primary Endpoint
- Primary Safety Endpoint: Device or procedure related serious adverse events
- Status
- Recruiting
- Last Updated
- last month
Overview
Brief Summary
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.
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Chronic heart failure, defined as:
- •Symptoms of HF requiring current (intermittent or continuous) treatment with diuretics for \>30 days, AND
- •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
- •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.
- •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.
- •LVEF ≥50% (site-determined by transthoracic echocardiography) within the past 6 months.
- •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.
Exclusion Criteria
- •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 screening.
- •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.
- •Presence of or prior history of mechanical circulatory support for HF.
- •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.
- •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.
- •Body mass index (BMI) \>45 kg/m
Arms & Interventions
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.
Intervention: Greater Splanchnic Nerve Ablation
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.
Intervention: Sham Control
Outcomes
Primary Outcomes
Primary Safety Endpoint: Device or procedure related serious adverse events
Time Frame: 1 Month
Evaluation of device or procedure-related serious adverse events at 1-month follow-up based on Clinical Events Committee (CEC) assessment
Primary Efficacy Endpoint: KCCQ (6 months)
Time Frame: Baseline through 6-months
Assessment of change in Kansas City Cardiomyopathy Questionnaire (KCCQ) from baseline to 6-month follow up visit
Primary Efficacy Endpoint: 6MWT (6 months)
Time Frame: Baseline through 6 months
Assessment of change in Six Minute Walk Test (6MWT) from baseline to the 6-month follow up visit
Secondary Outcomes
- 6MWT (24-months)(Baseline through 24-months)
- Pulmonary Capillary Wedge Pressure (PCWP)(Baseline through 1-month)
- Stress blood volume(Baseline through 1-month)
- NT-proBNP(Baseline through 24-months)
- KCCQ (24-months)(Baseline through 24-months)
- Time to first heart failure event(Treatment through 24-months)
- Incidence of heart failure events(Treatment through 24-months)
- Hierarchical composite endpoint (12-months)(Baseline through 12-months)
- Incidence of serious device related cardiac or vascular events(Treatment through 12- and 24-months)
- Device or procedure related pain(Treatment through 24-months)
- Orthostatic hypotension(Treatment through 12- and 24-months)
- Acute Kidney Injury (AKI)(Baseline through 12-and 24-months)
- Glomerular Filtration Rate (GFR)(Baseline through 12- and 24-months)
- Adverse Events(Procedure through 12- and 24-months)
- Mortality(Procedure through 6-, 12- and 24-months)