Splanchnic Nerve Block for Therapy of Chronic Heart Failure (Splanchnic III)
Primary Purpose
Chronic Heart Failure
Status
Completed
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Splanchnic nerve block
Sponsored by
About this trial
This is an interventional treatment trial for Chronic Heart Failure focused on measuring heart failure, exercise, splanchnic nerve block
Eligibility Criteria
Inclusion Criteria:
- Followed at DUMC for known or suspected diagnosis of HF (NYHA stage 2-4, Class C-D), including patients on inotropic medication
- Systolic blood pressure (SBP) > 100 mmHg
- History of HF hospitalization or ER visit or iv diuretic use in last 12 months.
- Patients will be included regardless of left ventricular ejection fraction.
Exclusion Criteria:
- Anticoagulation at the time the procedure or in case of recent warfarin use an INR >1.4. Anticoagulation includes: warfarin, or novel oral anticoagulants like dabigatran, rivaroxaban, apixaban, endoxaban or full dose intravenous heparin products or bivalirudin and fondaparinux). Antiplatelet agents besides aspirin such as ticagrelor, prasugrel, Plavix are also considered to be a contraindication if used at time point of procedure.
- Immunosuppressive medications for solid organ transplant
- Acute MI (STEMI or Type I NSTEMI) within 7 days?
- Evidence of progressive cardiogenic shock within 48 hours
- Restrictive cardiomyopathy
- Constrictive pericarditis
- Pericardial effusion with evidence of tamponade
- Severe valvular stenosis requiring intervention
- Known history of an increased bleeding risk
- Thrombocytopenia (< 50,000)
- End-stage renal disease CKD stage 5 due to primary renal pathology
Sites / Locations
- Duke University Medical Center
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Splanchnic nerve block
Arm Description
Outcomes
Primary Outcome Measures
Peak Exercise Wedge Pressure
Measured with cardiopulmonary exercise testing
Peak Pulmonary Arterial Pressure
Measured on exercise cardiopulmonary stress test
Absence of Nerve Block Related Complications
Assessment of orthostasis, gastrointestinal symptoms were observed
Secondary Outcome Measures
Peak Oxygen Uptake
Resting Wedge Pressure
Assessed with right heart cath
Resting Central Venous Pressure
Assessed with right heart cath
Resting Pulmonary Arterial Pressure
Assessed on right heart catheterization
Dyspnea - Visual Analog Scale (VAS)
The VAS for dyspnea has a range of 0 to 100, where 0 corresponds to the patient's subjective feeling of "I Can Breathe Normally" and a score of 100 corresponds to "I Can't Breathe At All."
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT04575428
Brief Title
Splanchnic Nerve Block for Therapy of Chronic Heart Failure (Splanchnic III)
Official Title
Splanchnic Nerve Block for Therapy of Chronic Heart Failure (Splanchnic III)
Study Type
Interventional
2. Study Status
Record Verification Date
May 2023
Overall Recruitment Status
Completed
Study Start Date
February 5, 2020 (Actual)
Primary Completion Date
June 16, 2021 (Actual)
Study Completion Date
June 16, 2021 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Duke University
4. Oversight
Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
Splanchnic vasoconstriction may contribute to decompensation of chronic heart failure (HF) via volume redistribution from the splanchnic vascular bed to the central compartment. This is a sympathetically mediated reflex and can be interrupted through a splanchnic nerve block (SNB). We hypothesize that interruption of the efferent/afferent innervation of the splanchnic vasculature will decrease cardiac congestion in patients presenting with HF. Based on preliminary safety and efficacy data in acute and chronic heart failure patients with temporary (<24 h) SNB. Now we will apply a prolonged SNB in chronic heart failure patients using a long acting agent. We will test the effects of SNB on long term exercise capacitance.
Detailed Description
Activation of splanchnic nerves results in vasoconstriction and reduces splanchnic capacitance, therefore recruiting blood volume into the central circulation. In heart failure, a reduced splanchnic vascular capacitance could be the mechanism underlying symptoms of exercise intolerance and could predispose to rapid decompensation with external fluid intake or retention. A compromised vascular reservoir is likely unable to buffer shifts of fluid and actively contributes to the acute or chronic expulsion of fluid from the splanchnic vascular compartment to the central thoracic compartment. The redistribution of blood volume into the central circulation may lead to a sudden rise in pulmonary and left-sided cardiac pressures in HF. This makes the splanchnic vascular compartment an attractive target in heart failure. Our preliminary proof-of-concept work in patients with acute decompensated and chronic heart failure showed promise for the concept of splanchnic nerve modulation in heart failure. In a series of two small first-in-human studies for acute decompensated heart failure (N=13) (NCT02669407) and chronic heart failure (N=17) (NCT03453151), we found that a splanchnic nerve block (SNB) with lidocaine (90 min duration of action) and ropivacaine (24 hours duration of action) acutely reduced resting and exercise-induced intra-cardiac filling pressures, associated with improved patient symptoms and functional capacity.
The present study will be a prospective open-label pilot study to help establish feasibility, safety and enable dose finding for botulinumtoxin. Following a baseline invasive (right heart catheterization) cardiopulmonary exercise testing (CPX) patients will undergo unilateral celiac plexus block, followed by repeat hemodynamic testing. Functional testing at baseline and follow up will be supplemented by measures of blood volume and autonomic tone.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Heart Failure
Keywords
heart failure, exercise, splanchnic nerve block
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
5 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Splanchnic nerve block
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Splanchnic nerve block
Intervention Description
Percutaneous splanchnic nerve block
Primary Outcome Measure Information:
Title
Peak Exercise Wedge Pressure
Description
Measured with cardiopulmonary exercise testing
Time Frame
4 weeks
Title
Peak Pulmonary Arterial Pressure
Description
Measured on exercise cardiopulmonary stress test
Time Frame
4 weeks
Title
Absence of Nerve Block Related Complications
Description
Assessment of orthostasis, gastrointestinal symptoms were observed
Time Frame
8 weeks
Secondary Outcome Measure Information:
Title
Peak Oxygen Uptake
Time Frame
4 weeks
Title
Resting Wedge Pressure
Description
Assessed with right heart cath
Time Frame
4 weeks
Title
Resting Central Venous Pressure
Description
Assessed with right heart cath
Time Frame
4 weeks
Title
Resting Pulmonary Arterial Pressure
Description
Assessed on right heart catheterization
Time Frame
4 weeks
Title
Dyspnea - Visual Analog Scale (VAS)
Description
The VAS for dyspnea has a range of 0 to 100, where 0 corresponds to the patient's subjective feeling of "I Can Breathe Normally" and a score of 100 corresponds to "I Can't Breathe At All."
Time Frame
4 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Followed at DUMC for known or suspected diagnosis of HF (NYHA stage 2-4, Class C-D), including patients on inotropic medication
Systolic blood pressure (SBP) > 100 mmHg
History of HF hospitalization or ER visit or iv diuretic use in last 12 months.
Patients will be included regardless of left ventricular ejection fraction.
Exclusion Criteria:
Anticoagulation at the time the procedure or in case of recent warfarin use an INR >1.4. Anticoagulation includes: warfarin, or novel oral anticoagulants like dabigatran, rivaroxaban, apixaban, endoxaban or full dose intravenous heparin products or bivalirudin and fondaparinux). Antiplatelet agents besides aspirin such as ticagrelor, prasugrel, Plavix are also considered to be a contraindication if used at time point of procedure.
Immunosuppressive medications for solid organ transplant
Acute MI (STEMI or Type I NSTEMI) within 7 days?
Evidence of progressive cardiogenic shock within 48 hours
Restrictive cardiomyopathy
Constrictive pericarditis
Pericardial effusion with evidence of tamponade
Severe valvular stenosis requiring intervention
Known history of an increased bleeding risk
Thrombocytopenia (< 50,000)
End-stage renal disease CKD stage 5 due to primary renal pathology
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marat Fudim, MD, MHS
Organizational Affiliation
Duke Universtiy
Official's Role
Principal Investigator
Facility Information:
Facility Name
Duke University Medical Center
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
12. IPD Sharing Statement
Plan to Share IPD
No
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Splanchnic Nerve Block for Therapy of Chronic Heart Failure (Splanchnic III)
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