Clinical trial NCT04592445: Endovascular Ablation of the Right Greater Splanchnic Nerve in Subjects Having HFpEF
Official title: ENDOVASCULAR ABLATION OF THE RIGHT GREATER SPLANCHNIC NERVE IN Endovascular Ablation of the Right Greater Splanchnic Nerve in Subjects Having HFpEF: Feasibility Study: Randomized Controlled Feasibility Trial- Rebalance HF Study
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: NA
Conditions: Heart Failure With Preserved Ejection Fraction
Lead sponsor: Axon Therapies, Inc.
Sponsor class: INDUSTRY
First posted: 2020-10-19
Enrollment: 80
Sex: ALL
Minimum age (years): 40
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Subjects randomized 1:1 (treatment to sham control); cross-over offered
Primary purpose: TREATMENT

Brief summary: The objective of this clinical evaluation is to assess the safety and initial effectiveness of catheter-based unilateral ablation of the right greater splanchnic nerve (GSN) in subjects having heart failure with preserved ejection fraction (HFpEF).

Detailed description: This clinical investigation is a prospective, multi-center randomized, sham control, double blinded feasibility clinical study. Both the subject and the noninvasive cardiologist that is caring for the subject will be blinded to the assigned cohort (treatment or sham). The interventional cardiologist who performs the index procedure will not be blinded.

Subjects who meet the eligibility criteria and are enrolled will be randomized 1:1 to either ablation of the right GSN using the Axon System (treatment cohort) or sham (control cohort) at the time of the procedure.

This study will enroll up to 100 subjects at an anticipated 20 US sites. Subject follow up is at 1, 3, 6, and 12 months

Eligibility criteria: Inclusion Criteria:

1. Subjects ≥ 40 years of age
2. Chronic heart failure defined as at least one of the following:

   1. Symptoms of HF requiring current treatment with diuretics (intermittent or continuous) for \> 30 days, AND
   2. 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
   3. \> 1 HF hospital admission (with HF as the primary, or secondary diagnosis);

      * OR - treatment with intravenous (IV) diuretics, or intensification of oral diuresis for HF in a healthcare facility within the 12 months prior to study entry;
      * OR - NT-pro BNP value \> 150 pg/ml in normal sinus rhythm, \> 450 pg/ml in atrial fibrillation within the past 6 months;
      * OR - BNP value \> 50 pg/ml in normal sinus rhythm, \> 150 pg/ml in atrial fibrillation within the past 6 months.
3. Ongoing stable GDMT HF management (unless unable to tolerate GDMT) and management of potential comorbidities according to the 2017 ACCF/AHA Guideline for the Management of Heart Failure, with no significant changes \[\>100% increase or 50% decrease\] for a minimum of 1 month prior to screening, that is expected to be maintained without change for at least 3 months.
4. LVEF ≥ 50 % (site determined by TTE) in the past 3 months.
5. Site determined elevated PCWP documented by right heart catheterization by PCWP ≥ 25 mmHg during supine ergometer exercise

   a. PCWP to be evaluated by a Swan Ganz procedure performed either prior to the day of the index procedure or on the day of the index procedure
6. 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 past 3 months; CABG in past 3 months, or current indication for coronary revascularization.
2. Cardiac Resynchronization Therapy initiated within the past 3 months prior to screening.
3. Advanced heart failure defined as one or more of the below:

   1. ACC/AHA/ESC Stage D heart failure, non-ambulatory NYHA Class IV HF
   2. Cardiac index \< 2.0 L/min/m2
   3. Inotropic infusion (continuous or intermittent) for LV EF\< 30% within the past 6 months prior to screening
   4. Subject is on the cardiac transplant waiting list
4. BMI \> 45 kg/m2
5. Inability to perform 6-minute walk test (distance \< 100 meters), OR ability to perform 6-minute walk test distance \> 450 meters.
6. Admission for HF within the 30 days prior to planned index procedure.
7. In the last 3 years an ejection fraction (EF) below 40
8. Systolic BP \< 100 mmHg or \> 170 mmHg despite appropriate medical management.
9. Symptomatic orthostatic hypotension or orthostatic hypotension requiring treatment (orthostatic hypotension is defined as systolic blood pressure decrease of \>20mmHg and/or increase in heart rate \>20 bpm upon going from supine to standing position).
10. Arterial oxygen saturation \< 90 % on room air.
11. Presence of significant valve disease defined by the site cardiologist as:

    1. Mitral valve stenosis defined as \<1.5 cm2 (or greater than mild)
    2. Mitral valve regurgitation defined as grade \> 3+ MR
    3. Tricuspid valve regurgitation defined as grade \> 3+ TR
    4. Aortic valve disease defined as \> 3+ AR or \> severe AS
12. Hypertrophic cardiomyopathy, restrictive cardiomyopathy, constrictive pericarditis, cardiac amyloidosis, or other infiltrative cardiomyopathy (e.g., hemochromatosis, sarcoidosis)
13. 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.
14. Mean resting right atrial pressure (RAP) \> 20 mmHg based upon screening right heart catheterization.
15. History of severe liver cirrhosis
16. Dialysis dependent; or estimated-GFR \<25 ml/min/1.73 m2 by MDRD equation.
17. Baseline status of persistent atrial fibrillation with resting HR \>100 beats per minute that could obfuscate RHC interpretation.
18. Chronic pulmonary disease requiring continuous home oxygen OR hospitalization for exacerbation (including intubations) in the 12 months before study entry OR known history of GOLD Class II or higher COPD.
19. Currently participating in conflicting investigational drug or device study.
20. Life expectancy \<12 months for non-cardiovascular reasons.
21. Any condition, or history of illness or surgery that, in the opinion of the Investigator, might confound the results of the study or pose additional risks to the patient.
22. Females who are not pregnant or lactating and not or planning to become pregnant for the duration of the study during the next year.

Primary outcomes:
measure: Primary Outcome Endpoint
timeFrame: 1 Month
measure: Primary Safety Outcome
timeFrame: 1 month
Secondary outcomes:
measure: Secondary Outcome Endpoints
timeFrame: 1, 3, 6, and 12 months
measure: Secondary Outcome Endpoints
timeFrame: 1, 3, 6, and 12 months
measure: Secondary Outcome Endpoints
timeFrame: 1, 3, 6, and 12 months
measure: Secondary Outcome Endpoints
timeFrame: 1 month
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Cardiology PC
state: Alabama
city: Phoenix
country: United States
facility: Arizona Cardiovascular Research Center
state: Arizona
city: La Jolla
country: United States
facility: Scripps Health
state: California
city: San Francisco
country: United States
facility: University of California, San Francisco
state: California
city: Chicago
country: United States
facility: Bluhm Cardiovascular Institute of Northwestern University
state: Illinois
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: Springfield
country: United States
facility: Prairie Education and Research Cooperative
state: Illinois
city: Houma
country: United States
facility: Cardiovascular Institute of the South
state: Louisiana
city: Ann Arbor
country: United States
facility: Michigan Medicine, University of Michigan
state: Michigan
city: Rochester
country: United States
facility: Mayo Clinic
state: Minnesota
city: New York
country: United States
facility: Weill Cornell Medicine
state: New York
city: New York
country: United States
facility: Icahn School of Medicine at Mount Sinai
state: New York
city: New York
country: United States
facility: Center for Advanced Cardiac Care, Columbia University Medical Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Columbus
country: United States
facility: Ohio State University Wexner Medical Center
state: Ohio
city: Charleston
country: United States
facility: Medical University of South Carolina, Gazes Cardiac Research Institute
state: South Carolina
city: Richmond
country: United States
facility: Virginia Commonwealth University Medical Center
state: Virginia
Study officials:
References: