Endovascular Ablation of the Right Greater Splanchnic Nerve in Subjects Having HFpEF

Официальное название

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

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство 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 usi
• Устройство 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.

Первичные конечные точки

• Primary Safety Endpoint: Device or procedure related serious adverse events [Срок оценки: 1 Month]
• Primary Efficacy Endpoint: KCCQ (6 months) [Срок оценки: Baseline through 6-months]
• Primary Efficacy Endpoint: 6MWT (6 months) [Срок оценки: Baseline through 6 months]

Вторичные конечные точки (12)

• Pulmonary Capillary Wedge Pressure (PCWP) [Срок оценки: Baseline through 1-month]
• Stress blood volume [Срок оценки: Baseline through 1-month]
• NT-proBNP [Срок оценки: Baseline through 24-months]
• KCCQ (24-months) [Срок оценки: Baseline through 24-months]
• 6MWT (24-months) [Срок оценки: Baseline through 24-months]
• Time to first heart failure event [Срок оценки: Treatment through 24-months]
• Incidence of heart failure events [Срок оценки: Treatment through 24-months]
• Hierarchical composite endpoint (12-months) [Срок оценки: Baseline through 12-months]
• Incidence of serious device related cardiac or vascular events [Срок оценки: Treatment through 12- and 24-months]
• Device or procedure related pain [Срок оценки: Treatment through 24-months]
• Orthostatic hypotension [Срок оценки: Treatment through 12- and 24-months]
• Acute Kidney Injury (AKI) [Срок оценки: Baseline through 12-and 24-months]

Критерии участия

Критерии включения

• 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.

Критерии исключения

• 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/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 change from supine to standing decrease of >10mmHg in the absence of a HR increase >15bpm
• Postural orthostatic tachycardia syndrome or preload insufficiency syndrome.
• 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.
• Left ventricular EF <40% within the 3 years prior to screening unless reduced EF was transient and associated with an acute event.
• 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.
• 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 <25 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.
• Any of the following measured by screening right heart catheterization:

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

Exclusion Criteria Assessed During the index procedure:

• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Двойное слепое

Основная цель

Лечение

Центры проведения

США · 20 центров

• Cardiology PC — Birmingham
• Arizona Cardiovascular Research Center — Phoenix
• Scripps Health — La Jolla
• University of California, San Francisco — San Francisco
• Bluhm Cardiovascular Institute of Northwestern University — Chicago
• University of Chicago Medical Center — Chicago
• Prairie Education and Research Cooperative — Springfield
• Ascension St. Vincent - Cardiovascular Research Institute — Indianapolis
• … и ещё 12 центров

Публикации

• Ziaeian B, Fonarow GC. Epidemiology and aetiology of heart failure. Nat Rev Cardiol. 2016 Jun;13(6):368-78. doi: 10.1038/nrcardio.2016.25. Epub 2016 Mar 3. PMID 26935038
• Benjamin EJ, Virani SS, Callaway CW, Chamberlain AM, Chang AR, Cheng S, Chiuve SE, Cushman M, Delling FN, Deo R, de Ferranti SD, Ferguson JF, Fornage M, Gillespie C, Isasi CR, Jimenez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Lutsey PL, Mackey JS, Matchar DB, Matsushita K, Mussolino ME, Nasir K, O'Flaherty M, Palaniappan LP, Pandey A, Pandey DK, Reeves MJ, PMID 29386200
• Gheorghiade M, Vaduganathan M, Fonarow GC, Bonow RO. Rehospitalization for heart failure: problems and perspectives. J Am Coll Cardiol. 2013 Jan 29;61(4):391-403. doi: 10.1016/j.jacc.2012.09.038. Epub 2012 Dec 5. PMID 23219302
• Heidenreich PA, Bozkurt B, Aguilar D, Allen LA, Byun JJ, Colvin MM, Deswal A, Drazner MH, Dunlay SM, Evers LR, Fang JC, Fedson SE, Fonarow GC, Hayek SS, Hernandez AF, Khazanie P, Kittleson MM, Lee CS, Link MS, Milano CA, Nnacheta LC, Sandhu AT, Stevenson LW, Vardeny O, Vest AR, Yancy CW; ACC/AHA Joint Committee Members. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure: A Report of t PMID 35363499
• Lam CS, Donal E, Kraigher-Krainer E, Vasan RS. Epidemiology and clinical course of heart failure with preserved ejection fraction. Eur J Heart Fail. 2011 Jan;13(1):18-28. doi: 10.1093/eurjhf/hfq121. Epub 2010 Aug 3. PMID 20685685
• Shah KS, Xu H, Matsouaka RA, Bhatt DL, Heidenreich PA, Hernandez AF, Devore AD, Yancy CW, Fonarow GC. Heart Failure With Preserved, Borderline, and Reduced Ejection Fraction: 5-Year Outcomes. J Am Coll Cardiol. 2017 Nov 14;70(20):2476-2486. doi: 10.1016/j.jacc.2017.08.074. Epub 2017 Nov 12. PMID 29141781
• Steinberg BA, Zhao X, Heidenreich PA, Peterson ED, Bhatt DL, Cannon CP, Hernandez AF, Fonarow GC; Get With the Guidelines Scientific Advisory Committee and Investigators. Trends in patients hospitalized with heart failure and preserved left ventricular ejection fraction: prevalence, therapies, and outcomes. Circulation. 2012 Jul 3;126(1):65-75. doi: 10.1161/CIRCULATIONAHA.111.080770. Epub 2012 May PMID 22615345
• Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006 Jul 20;355(3):251-9. doi: 10.1056/NEJMoa052256. PMID 16855265

Идентификаторы

NCT: NCT04592445 · 09868

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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