Clinical trial NCT04575428
Conditions: Chronic Heart Failure
Keywords: heart failure, exercise, splanchnic nerve block
Sponsor: Duke University
Start date: 2020-02-05; Completion date: 2021-06-16
Enrollment: 5 participants; Allocation: NA; Intervention model: SINGLE_GROUP

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.

Arms: arm 1: None
Interventions: intervention 1: Splanchnic nerve block
Intervention descriptions: intervention 1: Percutaneous splanchnic nerve block

Protocol documents:
Prot_SAP_000.pdf: 
Splanchnic Nerve Block for Therapy of Chronic Heart Failure (Splanchnic III) 
Clinicaltrials.gov number: NCT04575428 
Duke IRB number: Pro00103788 
Date: May 1th 2023 


Research Abstract
Please type your Research Abstract here:
The Research Abstract should summarize the main points of your study in one paragraph. The following 
guidelines may help you:
1. Purpose and objective (1-2 sentences)
2. Study activities and population group (2-4 sentences)
3. Data analysis and risk/safety issues (1-2 sentences)
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 and improve renal function in patients presenting with HF.
We have already obtained preliminary safety and efficacy data in acute and chronic heart failure patients 
with temporary (<24 h) SNB. Now we would like to apply a prolonged SNB in chronic heart failure patients 
using a long acting agent.  
Research Summary
State your primary study objectives
1. We will determine if splanchnic nerve blockade decreases cardiac preload as measured by invasive
hemodynamics.
2. We will determine if splanchnic nerve blockade will improve invasive hemodynamics during exercise.
3. We will determine if splanchnic nerve blockade improves symptoms of shortness of breath.
State your secondary study objectives
N/A
Please select your research summary form:
Standard Research Summary Template
This is the regular (generic) research summary template which is required  for all regular applications (unless 
your protocol fits under the other research summary templates in this category).  Use of these instructions is 
helpful for ensuring that the research summary contains all necessary elements.
Standard Research Summary
Purpose of the Study
Objectives & hypotheses to be tested


1.  
2.  
3.  
We will determine if splanchnic nerve blockade decreases cardiac preload as measured by 
invasive hemodynamics.
We will determine if splanchnic nerve blockade will improve invasive hemodynamics during 
exercise.
We will determine if splanchnic nerve blockade improves symptoms of shortness of breath.
Background & Significance
Should support the scientific aims of the research
Heart failure (HF) is a leading cause of morbidity and mortality, affecting more than 6 million adults in the 
US alone.  Cardiovascular congestion with resultant limitation in physical activity is the hallmark of chronic 
1
and decompensated HF. While it is well-accepted that the extent of fluid volume congestion is closely 
associated with clinical outcomes 
, the concept of fluid and salt overload as the primary drivers of 
2-4
symptomatic decompensation (with resting or exercise-induced dyspnea) has been challenged.
 Notably, 
5,6
about 50% of patients gain only minor weight (<2pounds or <2kg based on the study) in the days prior to 
a hospitalization.
 Additionally, intracardiac filling pressures in patients with HF commonly start to 
7,8
increase before any significant weight changes occur preceding an admission for clinical decompensation.9,1
 In our own analysis of the ASCEND-HF trial, 26% of patients had no weight loss (+/-1kg change) and 
0
8% actually experienced weight gain (³1kg) during a HF hospitalization, suggesting that net volume loss is 
not necessary for symptomatic relief.
 
11 Taken together, an increase in central filling pressures 
occurs in many cases in the absence of weight gain or total body volume increase 4,12, which 
lead us and others to suggest a contribution of 
 to the mechanism of 
volume redistribution
cardiac decompensation
 
In chronic HF, cardiopulmonary congestion is the main determinant of exercise intolerance, which 
manifests itself as exertional dyspnea and/or fatigue.
 Many HF patients have normal hemodynamics 
13,14
at rest 
, but there is growing evidence of profoundly abnormal hemodynamic response to exercise 
15
characterized by rapid and marked elevation in filling pressures.
 Exercise-induced intra-cardiac 
13,16
decompensation, whether driven by fluid overload or volume redistribution, in most cases is only an 
intermittent phenomenon as pressures return to baseline values during recovery.  
       The abdominal compartment has been implicated as a key contributor to the complex 
pathophysiology of HF given that it is the main storage compartment of intravascular blood volume. The 
highly vascular organs such as the liver, spleen and bowel are able to “store” or “recruit” large blood 
volumes within minutes in and out of the splanchnic vascular compartment.
 Animal and human data 
17-20
indicates that these blood shifts can significantly alter cardiac and central vascular hemodynamics.
 
17-19 Th
e main regulatory system for the splanchnic vascular capacitance (“storage-space”) are post-
ganglionic sympathetic fibers originating from the celiac plexus which control arterial and 
 These post-ganglionic sympathetic fibers in the celiac plexus receive input from 
venous vascular tone.
pre-ganglionic sympathetic fibers travelling via splanchnic nerves.
 
21,22 Activation of splanchnic nerves 
results in vasoconstriction and reduces splanchnic capacitance, therefore recruiting blood 
 
volume into the central circulation.19,21 In HF, a reduced splanchnic vascular capacitance23,24 co
uld be the mechanism underlying symptoms of exercise intolerance and could predispose to 
A compromised 
rapid decompensation with external fluid intake or retention (Figure 1).5,16,25 
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 
5,6,26
in HF.
Prior Evidence: Mounting evidence questions the notion that congestion is merely the result of external 
volume overload or volume retention. Supportive evidence is provided by blood volume analysis using the I
-labeled human serum albumin indicator-dilution technique. Using this technology, studies found that 
131
chronic HF patients with persistent symptoms are in 35% of cases hypovolemic or euvolemic  and the 
4
same was even true for patients admitted for decompensated HF (34%).
 
27,28 The heterogeneity of clinical 
to explain increased filling pressures at rest 
presentation suggests the presence of an alternate mechanism 
or with exercise despite a lack of fluid retention.


Effective measures to decrease vascular congestion acutely or chronically remain an 
unmet clinical need. We recently identified the splanchnic nerves as potential contributors to 
the pathophysiology of HF and we proposed that a heightened splanchnic sympathetic tone 
contributes to cardiac decompensation and a short-term interruption of the splanchnic nerve 
signaling would reverse the process and thus alleviate HF sign and symptoms in select patients 
with acute and chronic HF.
 We first showed that splanchnic nerve stimulation results in acute 
5,6,24
hemodynamic changes, with a decrease in splanchnic vascular compliance and increase in cardiac preload.1
 HF is characterized by a heightened global sympathetic tone, yet untargeted pharmacological 
7,19
reduction in sympathetic tone can be insufficient to result in effective splanchnic vasodilation and be 
detrimental due to unintended cardiovascular effects.
 Consequently, a targeted reduction of the 
29
splanchnic sympathetic tone in chronic HF could provide a therapy for patients with cardiopulmonary 
congestion at a resting state or state of activity.
Our preliminary proof-of-concept work in patients with acute decompensated and chronic HF 
showed promise for the concept of splanchnic nerve modulation in HF (
).
 In a series of two 
Figure 2
38
small first-in-human studies for acute decompensated HF (N=13)
 (Late-Breaker at ESC-HF 2018, 
25,38
Vienna, Austria, 
) and chronic HF (N=17) (Young Investigator Competition, ESC-HF 2019, 
NCT02669407
Athens, Greece,
), we found that a splanchnic nerve block (SNB) with lidocaine (90 min 
 NCT03453151
duration of action) and ropivacaine (24 hours duration of action) acutely reduced resting and exercise-
 intra-cardiac filling pressures, associated with improved patient symptoms and functional 
induced
capacity.
Our two proof-of-concept studies and the well-established safety profile of permanent splanchnic 
nerve blockade in patients with intractable abdominal pain (e.g., due to pancreatitis or cancer) provide the 
foundation for our study.
 A body of literature (>3,000 published cases) on non-HF patients suggests 
30-33
that the side effects of permanent splanchnic nerve blockade (surgical or interventional via alcohol 
injection) are restricted to 48-h post procedure. Most common side effects include orthostatic hypotension 
(80%) followed by gastrointestinal symptoms (60%). Interestingly, transient orthostatic hypotension due 
an increase in splanchnic vascular storage capacity, is clinically prevented by aggressive pre-procedural 
hydration.
 Historically (1930-1950’s) surgical denervation of splanchnic nerves has also been applied in 
33
form of the so-called splanchnicectomy for treatment of uncontrolled hypertension. While it was shown to 
be effective to reduce sympathetic tone and reduce blood pressure, the discovery of antihypertensive 
medications made this surgical procedure obsolete.
 Long-term pharmacological blockade of the celiac 
34
plexus/splanchnic nerves with Botulinum toxin (BTX) has been previously reported to be safe and effective 
in a case of refractory hypertension.
 Finally, our group has extensive experience with neuromodulation 
35
which includes the application of BTX to epicardial fat pads for prevention of post-operative atrial fibrillation
 and stellate ganglion blockade for ventricular arrhythmias.
 
36
37,38 Together, published evidence and 
our data indicates the potential importance of splanchnic nerve modulation as a treatment for 
HF, providing a strong scientific premise for further investigation in this field. 
 
Design & Procedures
Describe the study, providing detail regarding the study intervention (drug, device, physical 
procedures, manipulation of the subject or the subject’s environment, etc.). Discuss justifications for 
placebo control, discontinuation or delay of standard therapies, and washout periods if applicable. 
Identify procedures, tests and interventions performed exclusively for research purposes or more 
frequently than standard of care. Include alternative therapies, concurrent therapies discontinued per 
protocol, risk benefit ratio, and use of tissue/specimens. Discuss monitoring during washout periods if 
applicable. Include brief description of follow-up, if any.
 
Study design. The present study will be a prospective open-label pilot study to help establish feasibility, 
safety and enable dose finding for BTX. The schedule of events is presented in 
. Following a 
Figure 3
baseline invasive (right heart catheterization) cardiopulmonary exercise testing (CPX) patients will undergo 
unilateral celiac plexus block (
), followed by repeat hemodynamic testing in the following 
Figures 2 and 4
90 minutes. Repeat CPX (with and without hemodynamic testing) will occur at 2, 4, 8 weeks. A 12 month 
phone call to investigate vital status, HF hospitalizations will conclude the study. Functional testing at 
baseline and follow up will be supplemented by a series of minimally invasive and non-invasive measures 
of static and dynamic blood volume distribution (radionuclear plethysmography, bioelectrance, hepatic vein 
ultrasound), congestion parameters (biomarkers, BVA), autonomic nervous tone (catecholamines, 


baroreflex, and heart rate variability) and symptom questionnaires (Likert and Visual Analog scale). Given 
high volume of patients and right heart catheterizations (>1,000 per year) and our experience with 
enrolling patients in the preliminary studies, we anticipate to complete recruitment within 2 years. 
Figure 3.  Study Flow
Table 1: Schedule of events (CS, clinical study; SOC, standard of care/clinical)
  
Required 
Assessment
Pre-
Procedu
re (Day 
1)
Baselin
e (Intr
a-
Proced
ure)
Block Post-
Block 
Procedu
re
48 
Hour
s
Week
1
Week 2 Week 4 Week 8 Mont
h 6
Mont
h 12
Vitals
(BP, HR, RR, 
SpO2, weight)
X (CS)
X(CS)
X(CS)
X(CS)
X(CS)
Orthostatic 
vitals
X(CS)
X(CS)
X(CS)
X (CS)
X (CS)
Non-Invasive 
Testing*
X(CS)
X(CS)
X(CS)
X (CS)
X (CS)
Pregnancy test
X (SOC)
Labs: BMP 
(SOC), pro-BNP 
(CS), CA-125 
(CS), urine 
sodium (CS),
X (CS
/SOC)
X (CS
/SOC)
X (CS
/SOC)
X (CS
/SOC)
X (CS
/SOC)
Labs
Renin,
Angiotensin 
II,     Vasopressi
n,
Plasma 
Catecholamines
X (CS)
X (CS)
X (CS)
X (CS)
X (CS)
X(CS) X(CS)
X(CS) X(CS)


Dyspnea and 
EQ-5D-3L 
Questionnaires
X (CS)
X(CS)
X(CS) 
X (CS)
X(CS) 
Six minute walk 
test
X (CS)
X(CS)
X(CS) 
X (CS)
X(CS) 
Blood volume - 
Daxor
X (CS)
X (CS)
Heart rate 
variability
X (CS)
X (CS)
X (CS)
X (CS)
X (CS)
X (CS)
Right Heart 
Cath (RHC)
X (CS, 
SOC)
X (CS)
Scintigraphy
X (CS)
X (CS)
Invasive CPX
(peak VO2) 
X (CS)
X (CS)
CPX (peak VO2)
X (CS)
X (CS)
Echocardiogram
X (CS)
X (CS)
X (CS)
X (CS)
X (CS)
Renal 
ultrasound (to 
be done by 
Marat)
X (CS)
X (CS)
X (CS)
X(CS) 
X (CS)
Splanchnic 
nerve block
X
(CS) 
Phone Call
X 
(CS)
X 
(CS)
X 
(CS)
X 
(CS)
*Non-Invasive Testing
Device Name
Approval
Indication
CardioSet
Investigational measures lung volume using impedance technology
ReDS unit
FDA
measures lung fluid content using radiofrequency 
waves
Sphygmocor
FDA
measures arterial stiffness through a brachial cuff
Bedside Ultrasound
FDA
performed of the heart, abdomen, kidney and 
diaphragm to assess left ventricular function, inferior 
vena cava dimensions and collapsibility, hepatic vein 
blood flow and portal vein flow and peripheral renal 
flow of the kidney
Musculoskeletal 
Ultrasound
FDA
Utilizes muscle metabolic imaging derived from point 
of care musculoskeletal ultrasound for muscle mass, 
intramuscular glycogen content and intramuscular 
adipose tissue content
InBody
FDA
Bioelectrical Impedance Spectroscopy: Segmental 
bioelectrical impedance spectroscopy (BIS) is another 
non-invasive way of assessing muscle quality 
assessment.
VO2Master Pro
FDA
compact, mobile and wireless (bluetooth) breath-by-
breath metabolic cart to assess the cardio-metabolic 
and cardio-respiratory capacity /effort during training 
(Rehab)
PhysioFlow 
Hemodynamics
FDA
non-invasive hemodynamic monitor. It provides 
continuous, accurate, reproducible and sensitive 
measurements of cardiac output, stroke volume, 
systemic vascular resistance and left cardiac work 
index.
Portalite and Moxy
Investigational
assessment of muscle- and brain mitochondrial 
function  during cardiopulomonary exercise testing. 
The device is developed to measure concentration 
changes of oxyhemoglobin and deoxyhemoglobin with 
near infrared light.
WHOOP strap 3.0
Investigational measures heart rate variability and  heart rate
Questionnaire
Dyspnea
7-point Likert scale and Visual Analog Scale
EQ-5D-3L
Quality of Life


Device Name
FDA Approval 
(Yes/No)
Indication
CardioSet
No
measures lung volume using impedance technology
ReDS unit
Yes
measures lung fluid content using radiofrequency 
waves
Sphygmocor
Yes
measures arterial stiffness through a brachial cuff
Bedside Ultrasound
Yes
performed of the heart, abdomen, kidney and 
diaphragm to assess left ventricular function, inferior 
vena cava dimensions and collapsibility, hepatic vein 
blood flow and portal vein flow and peripheral renal 
flow of the kidney
Musculoskeletal Ultrasound
Yes
Utilizes muscle metabolic imaging derived from point 
of care musculoskeletal ultrasound for muscle mass, 
intramuscular glycogen content and intramuscular 
adipose tissue content
InBody
Yes
Bioelectrical Impedance Spectroscopy: Segmental 
bioelectrical impedance spectroscopy (BIS) is another 
non-invasive way of assessing muscle quality 
assessment.
VO2Master Pro
No
compact, mobile and wireless (bluetooth) breath-by-
breath metabolic cart to assess the cardio-metabolic 
and cardio-respiratory capacity /effort during training 
(Rehab)
PhysioFlow Hemodynamics
Yes
non-invasive hemodynamic monitor. It provides 
continuous, accurate, reproducible and sensitive 
measurements of cardiac output, stroke volume, 
systemic vascular resistance and left cardiac work 
index.
Portalite and Moxy
No
assessment of muscle- and brain mitochondrial 
function  during cardiopulomonary exercise testing. 
The device is developed to measure concentration 
changes of oxyhemoglobin and deoxyhemoglobin with 
near infrared light.
WHOOP strap 3.0
No
measures heart rate variability and  heart rate
Testing procedures
Blood volume analysis and scintigraphy: Blood volume analysis will be performed using I131-
radiolabelled albumin. The injection of the drug and associated blood draws will be completed in the 
nuclear lab. Patients will have a baseline blood sample drawn (4ml). Then, patients will be injected the 
radiolabeled albumin. After 12, 16 and 20 minutes we draw additional blood samples. The blood samples 
will be processed at the Duke nuclear laboratory using the Daxor analyzer or sent to Daxor Inc. for 
processing. If sent to Daxor for processing we will only share deidentified blood samples. Samples will be 
labelled with case number. We will provide patients age, gender and weight, which are needed for data 
calculation.
Following injection of the agent, the patient will also receive a 
 (Multiple Gated Acquisition 
MUGA Scan
sca
) is a noninvasive tool for assessing the function of the heart. The 
 produces a moving image 
n
MUGA scan
of the beating heart but also allows to image the abdomen, and from this image several important features 
can be determined about the health of the cardiac ventricles and blood distribution. 
Following injection of the technetium99, patients will be placed under a scintigraphy camera which will pick 
up the counts of radiation over the chest and abdomen. We will record resting counts over both 
compartments (chest /abdomen). Then patient will perform up to 5 min low resistance leg exercise while 
supine on a stepper placed at bed end. Counts will be recorded over both compartments during exercise. 
Blood draws reported above will occur during resting recording. The exercise will occur after the 20 min 
blood draw is complete. Total duration of the study is anticipated to be 30 min. 
The I-131 (Volumex) will either be administered by the nuclear medicine technician or Marat Fudim, MD. 
Both have received training from the manufacturer. 
 
Nerve Block Procedure. The unilateral, left-sided, temporal bilateral celiac plexus block will be 
performed by the interventional pain specialty team in the catheterization laboratory, with continuous 
hemodynamic monitoring similarly to our previously published experience.
 The celiac plexus block will be 
24
performed under fluoroscopic guidance in the posterior chest wall (vertebral space L1) to guarantee 
maximal safety (
). We will use a mix of 3 ml of lidocaine 1.55 with 1:10000 epinephrine, 10 ml of 
Figure 2
0.5% ropivacaine and up to 1.5 U/kg of BTX Type A. Lidocaine with epinephrine is used for procedural 


safety to exclude intravascular injection. In the present study we will start at a lower dose of the BTX 
(dose finding). We will plan to increase dose or decrease per Kg unit does for Botox based on 4 week 
assessment. 
The dosing up titration scheme (Scenario 1) is as following:
1. The 1st and 2nd subject receiving the block splanchnic procedure - 75Units of Botox, (not more than 1.5
Units/kg) follow up at 2 weeks with CPX and 4 weeks with invasive CPX and 8 weeks with CPX
2.
 - if prior dose tolerated, no safety
The 3rd and 4th subject receiving the block splanchnic procedure
issues at 4 weeks than proceed with dose increase to: 100Units of Botox, (not more than 1.5Units/kg)
follow up at 2 weeks with CPX and 4 weeks with invasive CPX and 8 weeks with CPX
3.
 - Scenario 1: if prior dose tolerated, no
The 5th and 6th subject receiving the block splanchnic procedure
safety issue and satisfactory efficacy at 4 weeks than patient 5/6 will get injection of 100Units of Botox
again (not more than 1.5Units/kg) with follow up at 2 weeks with CPX and 4 weeks with invasive CPX and
8 weeks with CPX   Satisfactory efficacy is defined as >25% reduction with exercise wedge pressure
   Scenario 2: if prior dose tolerated, no safety issue and efficacy not satisfactory at 4 weeks than patient 5
/6 will get injection of 125Units of Botox (not more than 1.5Units/kg) with follow up at 2 weeks with CPX 
and 4 weeks with invasive CPX and 8 weeks with CPX. 
Dose down titration scheme is as following: If BP is too low (newly <90mmHg, independent of heart failure 
medication changes done clinically) or patient report orthostatic symptoms we will return for the next 
patient to the preceeding lower Botox dose. If symptoms of orthostasis of hypotension are experienced 
already at the lowest dose we will drop the injection dose to 50 Units (not more than 1.5U/kg) . The 
effects of ropivacaine are expected to occur as early as 15 minutes and last for 24h. The acute effects will 
serve as confirmation of procedural success and provide reassurance that BTX was injected in the right 
location. BTX is a neurotoxin that blocks cholinergic neurotransmission and offers temporary autonomic 
modulation via ganglionic block. The peak pharmacological properties of BTX are expected at 2 weeks post 
injection. The estimated duration of BTX effect is up to 4-6 months.39,40
Selection of Subjects
List inclusion/exclusion criteria and how subjects will be identified.
Subjects will be identified by screening the Duke University Medical Center or Duke Raleigh outpatient 
heart failure and catheterization clinic environments.  All study subjects will have an electively scheduled 
right heart cathetherization, 
with or without an invasive cardiopulmonary exercise. 
by the cardiologist, 
Subjects with Cardiomems device will already have the device in place prior to the electively scheduled 
right heart catheterization.  
Inclusion Criteria:
1. Age 18-90
2. Patients with or without Cardiomems device implanted
3. Followed at DUMC for known or suspected diagnosis of HF (NYHA stage 2-3, Class C-D), including patients
on inotropic medication
4. Systolic blood pressure (SBP) > 100mmHg
5. History of HF hospitalization or ER visit or IV diuretic use in the last 12 months.
6. Patients will be included regardless of left ventricular ejection fraction.
Exclusion Criteria:
1. Contraindicated medications:


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
2. HF medication regimen: Initiation of HF medications (in the 48 hours preceding the study) such as beta
blockers, ACEI, ARB, aldosterone receptor blockers, calcium channel blockers of any type, central
sympatholytics like clonidine, moxonidine,
       
3. Recent acute MI or hemodynamic instability:
Acute MI (STEMI or Type I NSTEMI) within 7 days.
·
Evidence of progressive cardiogenic shock within 48 hours
·
4. Certain forms of HF:
Restrictive cardiomyopathy
·
Constrictive pericarditis
·
Pericardial effusion with evidence of tamponade
·
Severe valvular stenosis requiring intervention
·
5. Severe bleeding risk:
Known history of an increased bleeding risk
·
Thrombocytopenia (< 50,000)
·
6. Significant comorbidities:
End-stage renal disease CKD stage 5 due to primary renal pathology
·
Severe scoliosis of the thoracic spine
·
History of lung disease other than asthma and COPD (like interstitial fibrosis, cystic fibrosis,
·
pneumonitis, lung cancer etc.)
Respiratory instability (dependent on >4 L nasal cannula for a saturation >90% SpO2)
·


Exclude severe fixed pulmonary hypertension
·
History of organ transplant (heart , lung, liver, pancreases, small bowel).
·
7. Pregnancy: patients of childbearing age will be tested with pregnancy tests, unless they had a hysterectomy
or removal of their ovaries.
8. Procedure
Unable to tolerate procedure as determined by  or investigator
Will be excluded if invasive hemodynamics on study date determine that the  does not have elevated filling
pressures at rest or stress. Following pressures/situations will exclude the : wedge pressure < 15mmHg (<
12mmHg on inotrope) at rest and < 25mmHg with peak stress (< 22 with inotropes) and greater than the central
venous pressure or  determined by study personnel to be at risk for nerve block related complications.
Subject Recruitment and Compensation
Describe recruitment procedures, including who will introduce the study to potential subjects. Describe 
how you will ensure that subject selection is equitable and all relevant demographic groups have access 
to study participation (per 45 CFR 46.111(a) (3)). Include information about approximately how many 
DUHS subjects will be recruited. If subjects are to be compensated, provide specific prorated amounts 
to be provided for expenses such as travel and/or lost wages, and/or for inducement to participate.
Potential subjects will be identified via two potential pathways. Research team will screen the 
outpatient scheduled RHC cases and send a recruitment letter to the subject once their primary 
care provider has agred to the study. The subject will be contacted over the phone if the 
subject has not replied to the letter in at least 10 days per policy. The subject will be provided 
with any additional information he/she wants. In a second scenario the primary provider 
approaches the study team with a potential case. In both cases the subject will be notified 
about being approached on the day of the study about a second approach in person by a heal 
care provider known to the patien for potential consent.
 Subjects will be informed that their participation is strictly voluntary. They will be assured that 
the decision to decline participation will have no impact on their care or the perceptions of their 
providers.
 The subject will be compensated for a total of $300 for their participation in this clinical study. 
The subjects will receive $100 at the following visits: Procedure visit, 2 week follow-up, and 2 
month visit.
Consent Process
Complete the consent section in the iRIS Submission Form.
Subject’s Capacity to Give Legally Effective Consent
If subjects who do not have the capacity to give legally effective consent are included, describe how 
diminished capacity will be assessed. Will a periodic reassessment occur? If so, when? Will the subject 
be consented if the decisional capacity improves?


1.  
2.  
1.  
2.  
1.  
2.  
3.  
4.  
5.  
6.  
3.  
4.  
5.  
6.  
1.  
Subject has to be able to understand the English language and understand the 
study process including all potential risk and benefits to the subject. Any subject 
where the study personnel or treatment team has cause for concern regarding 
the subject’s ability to understand the study process or follow the consent 
process capacity, will be excluded from the study.
This is a FDA regulated study, therefore, this eConsent platform will comply with 21 CFR Part 11 
requirements, which include regulations on electronic records and electronic signatures.
Study Interventions
If not already presented in #4 above, describe study-related treatment or use of an investigational 
drug or biologic (with dosages), or device, or use of another form of intervention (i.e., either physical 
procedures or manipulation of the subject or the subject’s environment) for research purposes.
The study subjects will participant in the following study tests and procedures:
Invasive Test:
Regional nerve block under fluoroscopic guidance: A solution of ropivacaine 12 cc (approximately 2.5 
 
teaspoons) and Botox 75-125 units (approximately 0.25 teaspoons), into the space around a nerve, called 
the splanchnic nerve, which controls the blood vessels in your intestines. These drugs will be delivered 
using a long needle placed between the patient's ribs in the mid-region of the back.  The placement of the 
needle will be performed by an anesthesiologist experienced with the needle placement, with the 
assistance of x-ray guidance. The subject's measurement will be monitored for 60 minutes post-block. 
Cardiopulmonary exercise:  The subject will exercise by pedaling on a bike in a supine position for about 
.  
2-5 minutes, before stopping to rest The catheter will remain in the subject's heart to measure pressures 
while exercising to provide  information about the subject's exercise ability.   
Non-Invasive Tests:
Vital Signs (Orthostatic vital signs)
Imaging with ultrasound, impedance, radiofrequency
Fluid content in the body and lungs:  The subject will wear a vest that emits radiofrequency waves 
to measure fluid content (ReDs Vest).  The InBody uses Bioelectrical Impedance Spectroscopy to 
determine fluid content in the subject's body.
Lung impedance: electrodes will be attached to the subject's upper back and chest to determine 
the intra-thoracic blood volume (CardioSet)
Arterial stiffness using a brachial cuff. A cuff will be applied to your arm, similar to a blood 
pressure cuff, and a hand held probe will be placed on your groin and arm.     The cuff will inflate 
and will measure pulse wave changes in your blood vessels (Sphygmocor)
Cardiac Hemodynamics: the PhysioFlow device measures the subject's cardiac output, stroke 
volume, systemic vascular resistance and left cardiac work index.
Oxygen Utilization: VO2 Master Pro  (Oxygen consumption) will be used to measure 
oxygen consumption during rest and exercise.  PortaLite and MOXY will measure 
oxygen concentration during exercise. 
 Heart Rate Variability: The WHOOP strap 3.0 will measure heart rate and heart rate 
variability and will be worn for approximately one hour.  
6 minute walk test to measure your exercise capacity and endurance.
Questionnaires about the subject's feeling about their shortness of breath and breathing at rest
Cardiopulmonary (CPX) Testing:  Exercise testing with the subject using an upright bike.  The subject 
will exercise at their maximum effort.  The subject will be monitored for exercise intolerance, shortness 
of breath, or pain in the chest. The subject will wear a face mask to measure oxygen intake and carbon 
dioxide output.
MUGA Scan: non-invasive imaging method to evaluate the function of your heart.  This scan will help 
determine more information about the health of the subject's  cardiac ventricles and blood distribution.
Laboratory Tests:
 
Blood Volume Analysis: Administration of a small amount of plasma protein, albumin, containing a 
small amount of radioactive iodine (injected through the PIV). The radioactive iodine labeled albumin 


2.  
3.  
1.  
2.  
3.  
protein (blood volume solution) will be administered through the PIV line. Blood samples will be 
  
withdrawn before administration of the blood volume solution and 12, 16 and 20 minutes after 
administration. The blood samples will be processed at the Duke Nuclear Lab
 
oratory using the Daxor 
Analyzer for further processing
Biomarkers: Blood samples will be taken before the procedure and after the procedure for analysis of NT 
pro-BNP (indication of worsening heart failure) and  CA-125 (indication of inflammation).   
Autonomic Nervous System regulators:  Blood samples will be taken in the catheterization lab before and 
after the splanchnic block.  The samples will be processed and sent out to labs that specialize in analyzing 
these samples for hormones angiotensin II, vasopressin, catecholamines, and metanephrines.
Risk/Benefit Assessment
Include a thorough description of how risks and discomforts will be minimized (per 45 CFR 46.111(a) (1 
and 2)). Consider physical, psychological, legal, economic and social risks as applicable. If vulnerable 
populations are to be included (such as children, pregnant women, prisoners or cognitively impaired 
adults), what special precautions will be used to minimize risks to these subjects? Also identify what 
available alternatives the person has if he/she chooses not to participate in the study. Describe the 
possible benefits to the subject. What is the importance of the knowledge expected to result from the 
research?
Procedural risks of splanchnic nerve blocks have been extensively studied. Risks 
associated with this anesthetic nerve block are uncommon. Patients undergoing 
this procedure have a small risk (<1%) risk of developing local anesthetic 
systemic toxicity as a complication of regional anesthesia. Symptoms include 
non-specific central nervous system effects (altered mental status, agitation, 
seizures) and cardiac arrest. We have now completed 28 cases in the first pilot 
trial using lidocaine/ropivacaine and found no acute or chronic complications.
 
Mild complications like local pain at injection site, orthostatic hypotension and 
gastrointestinal dysmotility are time limited and improve with resolution of the 
anesthetic block. Severe complications like pneumothorax possibly requiring a 
chest tube, aortic vessel puncture with retroperitoneal bleed or hematothorax 
and spinal cord injury with possible paralysis. These are very rare since 
placement of the needle occurs under fluoroscopic guidance.
 
Other minor risks can include (in order of report in literature and experience at 
Duke):
Pain at puncture site and intercostal neuralgia
Gastrointestinal dysmotility including diarrhea, constipation and abdominal cramping as well as 
nausea
Bleeding at puncture site
 
We will perform the splanchnic block for chronic heart failure, which is a new 
indication. The splanchnic nerve block has now been studied by us for acute
/chronic heart failure but not been studied in the setting of chronic disease. We 
do not expect unexpected side effects other than stated above but unexpected 
side effects cannot be excluded. For safety purposes subjects enrolled in this 
study will remain monitored for several hours after the SNB and re-examined at 
2 weeks.
 
Anticipated benefits to the subject include improvement in central vascular 
congestion with a reduction in cardiac preload and pulmonary arterial pressures 
as well as left sided filling pressures. A reduction in cardiac pressures is also 
likely to improve symptoms of congestion, including shortness of breath.
 


Further it is expected that a decongestion of the central veins and interruption 
of the cardiorenal reflex loop will result in an improvement in renal function as 
measured by urine output. This will further contribute to the decongestion of 
the subject’s vasculature.
 
While both of those effects are only temporary (up to 6 months, the benefit 
provided by the brief episode of decongestion can provide lasting symptomatic 
improvement.
 
Given prior pilot studies and theoretical framework we expect a symptomatic 
improvement of patients during the nerve block. Given that we have not seen 
any side effects in acute heart failure patients after the nerve block wore off we 
do not expect comparable effects in chronic heart failure patiens when their 
block wears off given similar pathophysiology.
Costs to the Subject
Describe and justify any costs that the subject will incur as a result of participation; ordinarily, subjects 
should not be expected to pay for research without receiving direct benefit.
All testing and services performed only for the purposes of the clinical study will 
be provided at no cost to the research subject. However, the subject or the 
subject’s health insurance or Medicare is responsible for all costs that are part 
of usual medical care that would have happened if the subject were not in the 
clinical study. If the subjects health insurance or Medicare requires any co-
payment, co-insurance, or deductible, the subject will be responsible for making 
that payment. Anything not paid by either the study sponsor or the subject’s 
health insurance company will be billed directly to the subject for payment.
Data Analysis & Statistical Considerations
Describe endpoints and power calculations. Provide a detailed description of how study data will be 
analyzed, including statistical methods used, and how ineligible subjects will be handled and which 
subjects will be included for analysis. Include planned sample size justification. Provide estimated time 
to target accrual and accrual rate. Describe interim analysis including plans to stop accrual during 
monitoring. Phase I studies, include dose escalation schema and criteria for dose escalation with 
definition of MTD and DLT.
Cynthia Green in the Duke Heart Center will be preforming the statistics for the 
Splanchnic III study. We will perform descriptive statistics. Statistical 
comparisons will be made using t-tests for continuous outcomes and chi square 
or fisher’s exact test. Unless otherwise specified, a two-sided 0.05 level of 
significance will be used to declare change in pre-and post-procedure variables 
different.
 There is no direct measure of technical success following attempted block of 
the splanchnic nerves. Procedural success to block the splanchnic nerves will be 
assumed in 70% of the cases based on the experience in splanchnic nerve 
blocks in patients with intractable cancer.
Data & Safety Monitoring


Summarize safety concerns, and describe the methods to monitor research subjects and their data to 
ensure their safety, including who will monitor the data, and the frequency of such monitoring. If a 
data monitoring committee will be used, describe its operation, including stopping rules and frequency 
of review, and if it is independent of the sponsor (per 45 CFR 46.111(a) (6)).
Due to the experimental nature of this intervention, data will be recorded after 
each subject completes the intervention for signs of unintended negative 
effects. These include hypotension, worsening renal function, or clinical 
deterioration. Additionally, subject’s electronic medical data will be screened for 
any traumatic complications from the nerve block at 2 weeks, and 6 months 
post-procedure.
Unanticipated severe adverse events will be reported to the IRB per IRB policy.
In accordance with federal regulations the PI will monitor for review, and promptly report to 
the IRB, appropriate institutional officials, sponsor, coordinating center and the appropriate 
regulatory agency head, all unanticipated problems involving risks to subjects or others that 
occur in the course of a subject’s participation in  research study, in accordance with  (45 CFR 
46.103(b)(5)(i) and 21 CFR 56.108(b)(1)), all AE reports will be reported per the DUHS IRB 
policies.
Privacy, Data Storage & Confidentiality
Complete the Privacy and Confidentiality section of the iRIS submission form.
Describe Role of External Personnel:
N/A

ICF_001.pdf: 
 
 
Official Title: 
Splanchnic Nerve Block for Therapy of Chronic Heart Failure (Splanchnic III)   
 
NCT:   
NCT04575428 
 
IRB Document Date:   
05/13/2022 
 


Consent To Participate In A Research Study
Splanchnic Nerve Blockade as Treatment of Chronic Heart 
Failure
Page 1 of 17                                                  Subject*Initials:______________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
You are being asked to take part in this research study because you have chronic heart failure.  Research 
studies are voluntary and include only people who choose to take part.  Please read this consent form 
carefully and take your time making your decision. As your study doctor or study staff discusses this 
consent form with you, please ask him/her to explain any words or information that you do not clearly 
understand.  We encourage you to talk with your family and friends before you decide to take part in this 
CONCISE SUMMARY
This study aims to test the effects of a nerve block on heart congestion and shortness of breath symptoms 
among patients with heart failure. You may be eligible for this study because you have heart failure and are 
scheduled to have a right heart catheterization performed.
You will undergo planned hemodynamic testing during the right heart catheterization procedure in the cath 
lab. The  hemodynamic testing measures the pressures from your heart.
The research study will require the injection of a mixture of an anesthetic drug (ropivacaine) with 
botulinumtoxin (Botox) on one side of your heart. This mixture will be injected into the space around a 
nerve, called the splanchnic nerve, which controls the blood vessels in your intestines. This drug will be 
delivered using a long needle placed between your ribs, in the mid region of your back. The placement of the 
needle will be performed by an anesthesiologist experienced with the needle placement, with the assistance 
of x-ray guidance. The ropivacaine/Botox mixture is a nerve blocking medicine and will stop working on its 
own after about 6 months.  
After the block, you will go home. You will be retested with a catheterization and/or a supine bike at 2, 4, 8 
weeks. Study participation also includes a call at 48 hours, 1 week, 6 and 12 months following your 
splanchnic nerve block procedure. 
The risks associated with the nerve block include local bleeding, pain and infection. The most serious 
complications include a pneumothorax (collapsed lung) and with use of Botox, potentially excessive 
weakness, difficulty swallowing and breathing, and aspiration pneumonia (pneumonia that develops from 
inhaling food or liquid into your lungs). There is also risk associated with the catheterization that is done at 
Week 4 for research purposes.  Risks of a right heart catheterization (RHC) include pain and bruising.  Rare 
risks of RHC include rhythym disturbances, clotting, heart attack and even death. The expected benefit is a 
short and long term drop in your heart pressures and improvement in shortness of breath and related 
symptoms. 
If you are interested in learning more about this study, please continue reading below.
DUHS IRB
IRB NUMBER: Pro00103788
IRB REFERENCE DATE: 05/13/2022
IRB EXPIRATION DATE: 05/21/2023


Consent To Participate In A Research Study
Splanchnic Nerve Blockade as Treatment of Chronic Heart 
Failure
Page 2 of 17                                                  Subject*Initials:______________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
research study.  The nature of the study, risks, inconveniences, discomforts, and other important 
information about the study are listed below.
Please tell the study doctor or study staff if you are taking part in another research study.
Dr. Dr. Marat Fudim  will conduct the study and it is funded by a  grant from the National Institutes of 
Health (NIH).Portions of Dr. Fudim’s and his research team’s salaries will be paid by this grant.  
WHO WILL BE MY DOCTOR ON THIS STUDY?
If you decide to participate, Dr. Marat Fudim will be your doctor for the study and will be in contact 
with your regular health care provider throughout the time that you are in the study and afterwards, if 
needed. 
WHY IS THIS STUDY BEING DONE?
The purpose of this study is to test an investigational procedure using a pair of drugs in patients with 
chronic heart failure. Heart failure presents a big problem to the person affected by it and to the whole 
health care system. Patients with heart failure tend to be re-admitted to the hospital frequently with fluid 
overload, shortness of breath and leg swelling. The investigators want to test an intervention that targets 
an unexplored mechanism to reduce congestion and improve symptoms. We want to understand if a 
temporary block of the splanchnic nerves (nerves to the abdomen), which has been found to cause 
vasoconstriction resulting in an increase in blood volume and congestion in your heart.  We believe that 
if we block the action of the splanchnic nerve, it will reduce congestion in your heart and allow you to 
breathe better. 
A splanchnic nerve block is not usually done in patients with chronic heart failure. In this study, the 
splanchnic nerve block is considered investigational. The investigators will be using a mixture of 
ropivacaine and Botox to block your splanchnic nerve in an effort to reduce your heart failure 
symptoms.  Both ropivacaine and Botox are traditionally used for other medical purposes.  Ropivacaine 
is a local anesthetic (numbing medication) normally used to prevent the feeling of pain before, during, or 
after surgery, a medical procedure, or childbirth.  Botox is a neurotoxin produced by bacterium, which 
will block nerves from producing a flaccid paralysis (weakness or paralysis and reduced muscle tone).  
Since Botox can reduce muscle tone it has been used commonly to reduce lines and wrinkles from a 
person’s face.  It has also been used medically to treat conditions such as neck spasms, overactive 
bladder and lazy eye.  Both of these drugs interact with the the brain, spinal cord and major nerves by 
inhibiting nerve impulses and in this study, they will together inhibit the splanchnic nerve actions on the 
abdomen.   
Recently, we conducted a study using ropivacaine, as an intervention to block the splanchnic nerve, on 
patients with acute and chronic heart failure. There were changes in heart pressures and symptomatic 
benefit to the patient. In all cases the nerve block was <24 hours in duration. We would like to explore 
whether patients with chronic heart failure would directly benefit from the intervention, if the effects of 
the block have a prolonged duration, up to 6 months. 
DUHS IRB
IRB NUMBER: Pro00103788
IRB REFERENCE DATE: 05/13/2022
IRB EXPIRATION DATE: 05/21/2023


Consent To Participate In A Research Study
Splanchnic Nerve Blockade as Treatment of Chronic Heart 
Failure
Page 3 of 17                                                  Subject*Initials:______________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
HOW MANY PEOPLE WILL TAKE PART IN THIS STUDY?
The maximum amount of people that will take part in this study will be 10 at Duke University Medical 
Center.
WHAT IS INVOLVED IN THE STUDY?
If you agree to be in this study, you will be asked to sign and date this consent form.  
Some of these procedures and tests are standard for patients with heart failure, and are not 
investigational. If you have already had these tests performed before, they may be used for the study if 
your study doctor determines they do not need to be repeated for study purposes. 
Your participation in this study is strictly voluntary. If you do not sign this consent form, you will 
continue to receive care, but not as a part of this study. Declining to participate will not have any 
adverse effects on your care, incursion of any penalty, or withholding of benefits to which you are 
entitled. If you volunteer for the study but change your mind, you simply need to inform the study staff. 
We will provide you contact information to notify us of this decision. If you are unable to reach the 
study staff, you can inform your primary treatment team and they will facilitate notifying the study team. 
If you withdraw from the study, you will return to your usual care without repercussion.
Pre-Procedure Testing (Day 1):
You will have the following tests and procedures done before undergoing the right heart catheterization 
with cardiopulmonary testing: 

Physical exam and medical history

Vital signs (blood pressure, heart rate, respiratory rate and oxygen level). This will include 
measuring your blood pressure while you are in a reclined position, in a seated position, in a 
standing position (orthostatic vitals).  Document whether you have shortness of breath while 
lending forward (Bendopnea).

Shortness of Breath Questionnaires: questions asked about your shortness of breath and how you 
are breathing while resting.

EQ-5D-3L Quality of Life Questionnaire which will allow you to rate your health-related quality 
of life about your mobility, self-care, usual activities, pain and discomfort, anxiety and 
depression, on how severe of a symptom. 

Blood and urine tests: 

6-Minute Walk Test: to measure your exercise capacity and endurance.

Testing your lungs for fluid content using ReDS unit, which emits radiofrequency waves to 
measure fluid content.

Measurement of lung impedance (CardioSet device), which will determine the intra-thoracic 
blood volume.
DUHS IRB
IRB NUMBER: Pro00103788
IRB REFERENCE DATE: 05/13/2022
IRB EXPIRATION DATE: 05/21/2023


Consent To Participate In A Research Study
Splanchnic Nerve Blockade as Treatment of Chronic Heart 
Failure
Page 4 of 17                                                  Subject*Initials:______________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345

InBody will measure the fluid content of your body. It uses either clip-on or stick-on electrodes 
on your fingers and/or ankles and is worn for approximately one hour. The technology is called 
impedance.

An investigational device called the VO2 Master Pro will be used to measure oxygen 
consumption during rest and exercise. This device is a mask that will be worn for approximately 
one hour and will transmit data to a device.

Oxygen saturation of the brain using non invasive patches on the temples. 

Arterial stiffness (Sphygmocor device) using a brachial cuff.  A cuff will be applied to 
your arm, similar to a blood pressure cuff, and a hand held probe will be 
placed on your groin and arm. The cuff will inflate and will measure pulse 
wave changes in your blood vessels.

WHOOP strap 3.0 (an investigational device). The WHOOP strap 3.0 will measure heart rate 
and heart rate variability and will be worn for approximately one hour. This device is a wrist 
watch.

A device called PhysioFlow will monitor cardiac output noninvasively using electrodes applied 
to your chest that will be worn for approximately one hour. 

Two investigational devices called PortaLite and MOXY will measure oxygen concentration 
during exercise. The device consists of a small and flexible probe. The probe is the only part of 
the device in contact with the patient's skin.

Blood volume analysis: Administration of a small amount of plasma protein, albumin, 
containing a small amount of radioactive iodine (injected through the PIV). An initial blood 
sample will be drawn from one PIV and a small amount of radioactive iodine mixed with a 
plasma protein will be injected into the other PIV. After a short wait for the radioactive iodine to 
circulate throughout your body, five more blood samples will be drawn from the peripheral 
intravenous (PIV) line over about half an hour. In total, about 15 milliliters (3 tablespoons) will 
be collected.

MUGA scan is a non-invasive imaging method to evaluate the function of your heart.  This scan 
will produce images/pictures of your heart beating.  We will also take pictures of your abdomen. 
This test will help our research team determine more information about the health of your 
cardiac ventricles and blood distribution.

Scintigraphy (radiation scan), is a diagnostic test that detects emitted radioisotopes absorbed 
by the body. It is used with a computer to capture this radiation with external detectors to form 
two-dimensional images.   
On the day of the procedure, you will arrive to the Duke University Cath Lab. After you have been 
checked in, the cath lab nurse will obtain a PIV for you before procedure lab draw.  We will then 
perform the blood volume analysis procedure.  The radioactive iodine labeled albumin protein (blood 
volume solution) will be administered through your PIV line.  Blood samples will be withdrawn before 
administration of the blood volume solution and 12, 16 and 20 minutes after administration.  The blood 
samples will be processed at the Duke Nuclear Laboratory or sent to Daxor for further processing.  If 
DUHS IRB
IRB NUMBER: Pro00103788
IRB REFERENCE DATE: 05/13/2022
IRB EXPIRATION DATE: 05/21/2023


Consent To Participate In A Research Study
Splanchnic Nerve Blockade as Treatment of Chronic Heart 
Failure
Page 5 of 17                                                  Subject*Initials:______________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
sent to Daxor, the blood samples will be given a deidentified label.  Your age, gender and weight, which 
are needed to calculate your total blood volume, will be shared with Daxor. 
Following the injection of the blood volume solution, you will then be injected with technetium99 (a 
contrast drug used during the MUGA scan). You will then be placed under a scintigraphy camera, which 
will pick up the counts of radiation over your chest and abdomen.  We will record your resting counts 
over both your chest and abdomen. You will perform up to 5 minutes of low resistance leg exercise 
while laying on a stepper placed at bed end. Counts will be recorded over both your chest and abdomen 
during exercise.  
A member of the study team will perform additional assessments, such as, vital signs, shortness of 
breath questionnaires before and after the 6-Minute Walk Test, lung fluid content, lung impedance and 
arterial stiffness.  We will also use the non-invasive devices to measure your heart rate variability before 
during and after the hemodynamic testing.
Eligibility Procedure:
You will have the following additional tests to determine you eligibility:

Right heart catheterization done as part of your usual medical care

Echocardiogram, a picture of the heart using sound waves

Cardiopulmonary exercise test, used to assess the performance of your heart and lungs at rest and 
during exercise
You will undergo the planned catheterization procedure that will be done as part of your routine medical 
care. The physicians will use your arm or your neck to access your veins. Patients who are having 
routine catheterization outside of this study may also have vein access through their leg. If vein access 
cannot be obtained through your arm or neck then you will be unable to continue in this study. 
If the pressure measurements from your heart meet study inclusion criteria, you will proceed with 
study-related activities.  You will first be asked to perform the Valsalva maneuver, in which you blow 
through a syringe for 30 seconds. This procedure is designed to put mild pressure on the abdomen and 
restrict venous blood return to your heart.  This will cause a temporary drop in your heart pressures.  
This is used as a standard of care procedure to test the autonomic nerve tone.  
We will ask you to exercise (pedal on a bike) in a supine, or flat on your back, position. This is called an 
invasive cardiopulmonary exercise. It will be done with a catheter in your heart.  You will petal the bike, 
using your best effort, for about 2-5 minutes, before stopping to rest.  The catheter remains in your heart 
to measure pressures while you exercise to provide us with detailed information about its exercise 
ability. 
DUHS IRB
IRB NUMBER: Pro00103788
IRB REFERENCE DATE: 05/13/2022
IRB EXPIRATION DATE: 05/21/2023


Consent To Participate In A Research Study
Splanchnic Nerve Blockade as Treatment of Chronic Heart 
Failure
Page 6 of 17                                                  Subject*Initials:______________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
If your cardiologist has not ordered the exercise test as part of your routine investigation, we will add an 
exercise component to your study. If patients do get an exercise test ordered by the cardiologist it is 
typically only one exercise test at a time. 
After the initial results from the right heart catheterizations with cardiopulmonary testing are complete, 
your eligibility will be evaluated based on the hemodynamic results (pressures in your heart) at rest and 
during stress.  These results will indicate whether you are congested.  It will also let the investigator 
know if your heart functions well. You will not be included in the study if it is determined that heart 
functions well or if the medical team is concerned about complications based on your results.  The 
information and blood samples that were collected and not yet processed will be discarded/destroyed. 
Splanchnic Block Procedures:
Once the necessary clinical information is obtained and satisfies all criteria, the investigator will begin 
the splanchnic nerve blockade procedure.  Under x-ray guided technology, the investigator will require 
the injection of lidocaine with epinephrine at the location of the splanchnic nerve.  This solution is 
injected first to ensure the proper location. Once the proper location has been confirmed, ropivacaine  10 
cc (approximately 2.5 teaspoons) and Botox 75-125 units (approximately 0.25 teaspoons) solution will 
be placed into the space around the splanchnic nerve,. These drugs will be delivered using a long needle 
placed between your ribs in the mid-region of your back. The placement of the needle will be performed 
by an anesthesiologist experienced with the needle placement, with the assistance of x-ray guidance. The 
ropivacaine/Botox mix is a numbing medicine and will stop working on its own after 6 months. 
The nerve block will be administered only on one side of your back.  After the anesthetic is delivered, 
you will be kept in the catheterization lab so that the blood pressures in the various parts of your heart 
can be monitored for 60 minutes. The catheters used to monitor these pressures will be the same as those 
required for your medically necessary procedure, but they will be left in place longer.  
Additional Tests and Monitoring:
We will carefully monitor your urine output for 3 hours before and 3 hours after your procedure. In 
addition, both before and after the investigational procedure, we will ask you to complete a 6-minute 
walk test (test of how far you can walk in 6 minutes) and a questionnaire about symptoms of shortness 
of breath. You will also receive blood tests. While blood is always drawn as part of your routine care, 
we will remove some extra blood from you (~15 ml- approximately 3 teaspoons) for the purposes of our 
study. Blood will be collected before your catheterization procedure and at the end of it. Blood collected 
at the end of the procedure is purely investigational and not part of routine care. Blood will be drawn 
from the catheter that is in your body and will not require extra blood draws. 
The day of the procedure, we will ask you to delay the administration of your morning dose of diuretics 
(for example, furosemide, Lasix, hydrochlorothiazide, Bumex, bumetanide). This is so we can determine 
the impact of the procedure on your kidney function. You will return to your regularly scheduled 
diuretics 3 hours after the procedure. 
DUHS IRB
IRB NUMBER: Pro00103788
IRB REFERENCE DATE: 05/13/2022
IRB EXPIRATION DATE: 05/21/2023


Consent To Participate In A Research Study
Splanchnic Nerve Blockade as Treatment of Chronic Heart 
Failure
Page 7 of 17                                                  Subject*Initials:______________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
As part of the study, Dr. Fudim and his study team will send your blood for study-related laboratory 
tests to a laboratory vendor (Mayo Clinic and Inter Science Institute) which specialize in analyzing 
blood samples for hormone levels in your blood. Blood samples will only be labeled with a subject 
identifier (study ID). By signing this consent form, you authorize Dr. Fudim to send your blood to the 
Mayo Clinic and Inter Science Institute and their designated affiliates.
Week 2, 4, 8 Follow Up: 
The study procedures of the first day will be repeated at 2 weeks following the splanchnic nerve block. 
At week 2 you will repeat a supine bike exercise. There will not be a heart catheterization procedure, so 
invasive pressures will not be measured at Week 2. If a Cardiomems is in place we will measure 
pressures non-invasively.
You will then return at week 4 for a repeat catheterization with exercise similar to the initial study day. 
This catheterization is performed for research purposes only.
At week 8 we will repeat the exercise without catheterization again 
If you have a Cardiomems in place we will access your hemodynamic data and review your 
hemodynamic tracings for the 2 months before the nerve block (if available) and through the 12 months 
after. 
You will also have the blood volume procedure repeated before the right heart catheterization 
procedure or review of your Cardiomems device, at the Week 4 visit.  The study doctor will 
administer a small amount of plasma protein containing a small amount of radioactive iodine.  An 
initial blood sample will be drawn and a small amount of radioactive iodine mixed with a plasma 
protein will be injected. After a short wait for the radioactive iodine to circulate throughout your 
body, three more blood samples will be drawn over about half an hour. In total, about 15 milliliters 
(3 teaspoons) will be collected. You will not have the blood volume procedure at the 1-2 month 
follow up visit.
After blood collection is complete, you will perform some low degree of exercise on a bike 
attached to the table in the radiology scanner.  We will take pictures of your abdomen and chest 
before and after the exercise. There is no additional Xray exposure. We are simply measuring the 
radioactivity emitted from your body and trying to understand where and how much blood is 
located in your abdomen. This activity will be done at baseline and at 1 months.
Before, during and after obtaining the hemodynamic heart values, the study team will perform 
additional tests. We will measure you vital signs including orthostatic vitals and bendopnea. You will 
have additional blood samples drawn before and after the procedure. These blood samples will 
measure functional/diagnostic and hormone levels.  A vest will be applied to your chest and will 
DUHS IRB
IRB NUMBER: Pro00103788
IRB REFERENCE DATE: 05/13/2022
IRB EXPIRATION DATE: 05/21/2023


Consent To Participate In A Research Study
Splanchnic Nerve Blockade as Treatment of Chronic Heart 
Failure
Page 8 of 17                                                  Subject*Initials:______________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
measure non-invasively what the lung fluid content is in your lungs. We will also use a technology, 
CardioSet, InBody and PhysioFlow to measure lung and belly fluid, and heart rate variability.
A cuff will be applied to your arm, similar to a blood pressure cuff, and a hand-held probe will be 
placed on your groin and arm. The cuff will inflate and will measure pulse wave changes in your 
blood vessels. The technology used for this is tonography using the Sphygmocor device. 
You will be allow to go home after all your tests and procedures have been completed.  
At 48 Hours, 1 Week, 6 Months and 12 Months Phone Follow Up:
A member of the study team will contact you by telephone ask you about your current health state 
and any possible adverse events you may have experienced since your last visit.
HOW LONG WILL I BE IN THIS STUDY?
Your active participation in this study will last for only 2 months. We will contact you several times, up 
to 12 months, after your procedure, by phone. If you have been admitted to an outside hospital, we will 
ask for permission to review the outside hospital and Duke Hospital medical records over the 12 months 
after the study. 
You can choose to stop participating at any time without penalty or loss of any benefits to which you are 
entitled. However, if you decide to stop participating in the study, we encourage you to talk to your 
doctor first.
Clinically relevant results of this research will be communicated with you. The potential new 
information gained will come from the cath lab procedure. The knowledge gained can be of value to 
your doctor as well.
WHAT ARE THE RISKS OF THE STUDY?
By participating in this study, you are at risk for the following side effects. You should discuss these 
with the study doctor and your regular health care provider if you choose. 
Splanchnic Nerve Blockade
Injection of ropivacaine in your back may cause some, all or none of the side effects listed below.
More likely side effects include:

local pain at injection site for hours to days, 

slight bleeding or bruising at injection site 

orthostatic hypotension (light-headedness on standing) for up to several hours. 

Also, commonly reported is gastrointestinal dysmotility (mild abdominal cramping, diarrhea or 
constipation) for up to several hours.
Less Likely complications include:
DUHS IRB
IRB NUMBER: Pro00103788
IRB REFERENCE DATE: 05/13/2022
IRB EXPIRATION DATE: 05/21/2023


Consent To Participate In A Research Study
Splanchnic Nerve Blockade as Treatment of Chronic Heart 
Failure
Page 9 of 17                                                  Subject*Initials:______________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345

collapsed lung, 

damage to the nerve between ribs causing pain, 

prolonged dizziness with standing for months

puncture of the aorta, which could cause bleeding into the space around the lungs or the 
abdomen. 

Further damage to the disc between vertebrae and paralysis of lower extremities due to spinal 
cord trauma or damage to one of the arteries supplying the spinal cord.
Patients undergoing this procedure have a small risk (<1%) risk of developing local anesthetic systemic 
toxicity.  Symptoms include non-specific central nervous system effects (altered mental status, agitation, 
seizures) and cardiac arrest. While we expect that the nerve block will improve your symptoms such as 
shortness of breath, we cannot exclude that the nerve block will make you feel worse. 
Injection of Botox in your back may cause some, all or none of the side effects listed below.

Bruising and pain at the injection site

Swelling and/or tenderness at the injection site

Rash

Flu-like symptoms

Headache

Nausea

Redness

Temporary muscle weakness
Serious reactions include the following:

Allergic reaction (anaphylaxis)

Prolonged dizziness

Paralysis

Fainting

Arrhythmias
If the Botox spreads beyond the treatment site of administration, it can cause botulism-like signs and symptoms, 
which include the following:

Breathing problems

Severe muscle weakness

Trouble swallowing

Speech disorders

Botox has a block box label issued by the FDA because of its potentially life-threatening side 
effect.
Risks of Right Heart Catheterization
The risk associated with this procedure, which requires the insertion of a tube (a catheter) into the 
arteries of your body. The following are possible risks of the catheterization procedure:
DUHS IRB
IRB NUMBER: Pro00103788
IRB REFERENCE DATE: 05/13/2022
IRB EXPIRATION DATE: 05/21/2023


Consent To Participate In A Research Study
Splanchnic Nerve Blockade as Treatment of Chronic Heart 
Failure
Page 10 of 17                                                  Subject*Initials:______________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
Uncommon < 10% (less than 1 in 10 chance), temporary and not severe unless otherwise stated 

Nausea or vomiting

Complications associated with the use of any pain or anxiety medication during or after the 
procedure

Complications at catheter insertion site in the groin (thigh)
o
Pain
o
Bruising
o
Hematoma (collection of blood outside a blood vessel)
Rare < 1% (less than 1 in 100 chance), temporary and not severe unless otherwise indicated

Heart rhythm disturbances, including bradycardia (a slowed heart rate)

Embolism - A blood clot or other substance is moved from the wall of your blood vessels, which 
travels downstream into small vessels, blocking blood flow and causing temporary or permanent 
damage to organs in the body. Clots are known to cause pulmonary embolism and may 
ultimately lead to incapacitation or death.

Complications at catheter insertion site in the groin (thigh)
o
Pseudoaneurysm (injury to the artery wall resulting in a build-up of blood under the skin)
o
Arteriovenous fistula (an abnormal connection or passageway between an artery and a 
vein)

Vascular complications requiring surgery
Very Rare <0.1% (less than 1 in 1000 chance)

Complications at catheter insertion site in the groin (thigh)
o
Infection
o
Significant bleeding

Cardiopulmonary arrest

Heart Attack

Death
Female Reproductive Risks
DUHS IRB
IRB NUMBER: Pro00103788
IRB REFERENCE DATE: 05/13/2022
IRB EXPIRATION DATE: 05/21/2023


Consent To Participate In A Research Study
Splanchnic Nerve Blockade as Treatment of Chronic Heart 
Failure
Page 11 of 17                                                  Subject*Initials:______________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
Being a part of this study while pregnant may expose the unborn child to significant risks, some of 
which may be currently unforeseeable. Therefore, pregnant women will be excluded from the study. If 
you are a woman of childbearing potential, a blood pregnancy test will be done (using 1 teaspoon of 
blood drawn from a vein by needle-stick), and it must be negative before you can continue in this study.  
This will be done as part of clinical routine and not part of the study, for your initial catheterization.  The 
pregnancy test that will be taken at the 4 week time point, will be part of the study.
Risks of Radiation from Imaging Tests
If you take part in this research, you may have one or more medical imaging tests which use radiation. 
These tests help the study doctor assess your medical condition and assess the effects of treatments. The 
study doctor will decide which tests you will have. The number of tests you will have depends upon how 
long you stay in the research study. To give you an idea about how much radiation you will get each 
time a test is done, we will make a comparison with an every-day situation. Everyone receives a small 
amount of unavoidable radiation each year called the 'natural background'. Some of this radiation comes 
from space and some from naturally-occurring radioactive forms of water and minerals. The chart below 
shows the tests that may be used in the research, and the amount of time in the natural background that 
gives an amount of radiation that is about equal to the amount of radiation each time you have the test.
A possible health problem seen with radiation exposure is the development of cancer later in life. This 
extra cancer risk is higher at younger ages and for girls and women. The extra lifetime risk of dying of a 
fatal cancer due to the radiation exposure from this research is also shown in the chart. At such low 
radiation exposures, scientists disagree about the amount of risk. These estimates are very uncertain, and 
there may be no extra risk at all.
 
Test
'Natural Background Time' 
Equivalent for Each Time 
This Test is Done
Extra Cancer Risk Each 
Time This Test is Done
0 Minutes
Negligible
Right Heart Catheterization
2 Months
Minimal
I-131 Albumin Blood Volume 
Study
2 Months
Minimal
MUGA Scan
2 Years
Very Low
 
RADIATION THERAPY: This research includes radiation therapy treatments. The test(s) in the table 
above will give you a small amount of additional radiation. However, the additional radiation from those 
tests is a very small fraction of the radiation from the therapy treatments, and are not expected to add 
any significant side effects or risk.
You may have a number of nuclear scans and fluoroscopy studies that are part of the regular 
care for your condition, and you would have them whether or not you participate in this 
DUHS IRB
IRB NUMBER: Pro00103788
IRB REFERENCE DATE: 05/13/2022
IRB EXPIRATION DATE: 05/21/2023


Consent To Participate In A Research Study
Splanchnic Nerve Blockade as Treatment of Chronic Heart 
Failure
Page 12 of 17                                                  Subject*Initials:______________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
research. These studies will not add to the risk of the research. However, if you have 
concerns about the overall radiation exposure, you should discuss them with your physician.
Risks of Scintigraphy
There are not any risk associated with the use of the scintigraphy.  It is just a device that measure the 
emitted radiation from the body.
Risks of Drawing Blood
Risks associated with drawing blood from your arm include momentary discomfort and/or bruising.  
Infection, excess bleeding, clotting, or fainting are also possible, although unlikely.
Drug and Food Interactions 
For your safety, you must tell the study doctor or nurse about all the prescribed medical foods and drugs, 
herbal products, over-the-counter (OTC) drugs, vitamins, natural remedies, and alcohol that you are 
taking before you start the study and before starting to take any of these products while you are on the 
study.
Risks of Washout 
There will be a brief period (<12 hours), where you will go without your regularly scheduled diuretic.
During this washout period, your symptoms of shortness of breath may get worse. Please discuss the 
washout period with the study doctor.
Risk of Withholding Medication
We will need to take you off oxygen, if you are receiving it, during administration of the shortness of 
breath questionnaire.  You will answer questions about shortness of breath several times over the course 
of study participation.  We will monitor oxygen levels in your blood closely to see if your oxygen 
saturation drops below 90%, which is considered to be the lower limit of normal. In that case, you will 
be re-started on oxygen. 
Risk of Echocardiography
There are not many anticipated risks associated with the echocardiographic evaluation of your heart 
during the study. However, some risks may include pressure on your chest from the probe that the 
technician uses to create pictures of your heart. Please tell the technician if you feel any pain or 
discomfort. We will use standard ultrasound technology. 
You could, however, possibly have a skin reaction from the application of the ultrasound gel.  An 
allergic reaction to the ultrasound gel is an uncommon problem.  
6-Minute Walk Test:
 There are some risks associated with taking the 6 minute walk test. During the 6 Minute Walk Test, you 
may experience difficulty breathing, shortness of breath, chest pains, dizziness, and or light headedness. 
DUHS IRB
IRB NUMBER: Pro00103788
IRB REFERENCE DATE: 05/13/2022
IRB EXPIRATION DATE: 05/21/2023


Consent To Participate In A Research Study
Splanchnic Nerve Blockade as Treatment of Chronic Heart 
Failure
Page 13 of 17                                                  Subject*Initials:______________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
You may also fall during the 6-minute walk. Your doctor and the study team will take all precautions 
possible to avoid and minimize these risks. Should any of these occur, your doctor may treat you with 
medicine and/or provide you with oxygen. 
Cardiopulmonary Exercise Test:
The cardiopulmonary exercise test is done as routine evaluation for heart failure. This might not been 
ordered as part of your test initially, but will be added on as part of the clinical study as it gives detailed 
information on the exercise ability and the limitations of exercise. This test will require you to exercise 
to your maximum, and is not associated with additional risks due to the exercise. The main risk during 
this procedure is related to the catheter being in the heart to record your pressures. These risks include 
bleeding and infection. The catheter will be inserted as part of routine care and should not present any 
additional risk inherent to the exercise test. 
Risks of ReDS Vest and Cardioset Devices and InBody and PhysioFlow
There is minimal risk associated with the ReDS vest as some may find wearing and the fitting of the 
device uncomfortable. Risks are associated with a mild rash where the electrodes are attached to your 
skin. Other devices are patches only, they emit a low electrical current that you will not feel and wont 
endanger your body or an implanted electrical device should you have one. 
Risks of Questionnaires
There are no physical risks associated with questionnaires for this study. There is, however, the potential 
risk of loss of confidentiality. Every effort will be made to keep your information confidential; however, 
this cannot be guaranteed. Some of the questions we will ask you as part of this study may make you 
feel uncomfortable. You may refuse to answer any of the questions and you may take a break at any 
time during the study. You may stop your participation in this study at any time.
There may be risks, discomforts, drug interactions or side effects that are not yet known.
ARE THERE BENEFITS TO TAKING PART IN THE STUDY?
If you agree to take part in this study, there may be direct medical benefit to you. You may experience 
rapid relief of your heart failure symptoms, including shortness of breath and fatigue; however, these 
improvements may only be temporary. Furthermore, we hope that in the future the information learned 
from this study will benefit other people with your condition. 
WHAT ALTERNATIVES ARE THERE TO PARTICIPATION IN THIS STUDY?
You do not have to be in this study to receive treatment for your heart failure.  If you decide not to be in 
this study, your primary team will proceed with the standard of care treatment of your heart failure, 
which typically involves drug treatment. 
WILL MY INFORMATION BE KEPT CONFIDENTIAL?
DUHS IRB
IRB NUMBER: Pro00103788
IRB REFERENCE DATE: 05/13/2022
IRB EXPIRATION DATE: 05/21/2023


Consent To Participate In A Research Study
Splanchnic Nerve Blockade as Treatment of Chronic Heart 
Failure
Page 14 of 17                                                  Subject*Initials:______________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
Participation in research involves some loss of privacy. We will do our best to make sure that 
information about you is kept confidential, but we cannot guarantee total confidentiality. Your personal 
information may be viewed by individuals involved in this research and may be seen by people 
including those collaborating, funding, and regulating the study. We will share only the minimum 
necessary information in order to conduct the research. Your personal information may also be given out 
if required by law. 
As part of the study, results of your study-related laboratory tests, x-rays, and procedures may be 
reported to the Duke Translational Research Institute and its affiliates. In addition, your records may be 
reviewed in order to meet federal or state regulations. Reviewers may include representatives from the 
Food and Drug Administration, the Duke University Health System Institutional Review Board, and 
others as appropriate. If any of these groups review your research record, they may also need to review 
your entire medical record. If this information is disclosed to outside reviewers for audit purposes, it 
may be further disclosed by them and may not be covered by federal privacy regulations.
As part of this study, you will be asked to have certain tests, x-rays, and/or procedures performed. Some 
of these tests, x-rays and/or procedures would have been done as part of your regular care. The study 
doctor will use these test results both to treat you and to complete this research.  These test results will 
be recorded in your medical record and will be reported to the research data office at Duke.  Results of 
tests and studies done solely for this research study and not as part of your regular care will also 
included in your medical record.
The study results will be retained in your research record for at least six years after the study is 
completed. At that time either the research information not already in your medical record may be 
destroyed or information identifying you will be removed from such study results at DUHS.  Any 
research information in your medical record will be kept indefinitely.
While the information and data resulting from this study may be presented at scientific meetings or 
published in a scientific journal, your name or other personal information will not be revealed.
Some people or groups who receive your health information might not have to follow the same privacy 
rules. Once your information is shared outside of DUHS, we cannot guarantee that it will remain private. 
If you decide to share private information with anyone not involved in the study, the federal law 
designed to protect your health information privacy may no longer apply to the information you have 
shared.  Other laws may or may not protect sharing of private health information.
WHAT ARE THE COSTS?
You or your insurance provider will be responsible and billed for all costs related to your routine 
medical care, including copayments and deductibles. Routine medical care services are those that you 
would have received for your condition if you were not participating in this research study. Not all 
services are covered by insurance.  Some procedures or scans may require pre-authorization by your 
DUHS IRB
IRB NUMBER: Pro00103788
IRB REFERENCE DATE: 05/13/2022
IRB EXPIRATION DATE: 05/21/2023


Consent To Participate In A Research Study
Splanchnic Nerve Blockade as Treatment of Chronic Heart 
Failure
Page 15 of 17                                                  Subject*Initials:______________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
insurance plan. We will notify you if we learn that a service is not covered by your insurance plan as 
part of the pre-authorization process. If it is not covered, you will be responsible for paying for it.  The 
amount of your out-of-pocket expense will depend on your insurance plan.  For beneficiaries with 
Medicare Advantage Plans, traditional Medicare is billed for the routine cost of a research study.  You 
may have more or higher co-pays than with a Medicare Advantage plan.  Please discuss the costs of the 
study with Dr. Fudim.  At your request, a Financial Counselor in the clinic may provide you with an 
estimate of costs for routine services.
The Duke University Grant has agreed to pay for services and procedures that are done solely for 
research purposes such as the Week 4 right heart catheterization.  Please talk with the Dr. Fudim or the 
study team about the specific services and procedures that the sponsor will pay for, and the ones for 
which you or your insurance will be responsible.
We will monitor your DUHS patient care charges to make sure that costs are directed appropriately.  If 
you have any questions or concerns about appropriate billing, contact your study team coordinator so 
that he/she can help find a resolution.
WHAT ABOUT COMPENSATION?
You will be receive up to $300 for your expenses related to your participation (parking, gas, and time). 
WHAT ABOUT RESEARCH RELATED INJURIES?
Immediate necessary medical care is available at Duke University Medical Center in the event that you 
are injured as a result of your participation in this research study. However, there is no commitment by 
Duke University, Duke University Health System, Inc., or your Duke physicians  to provide monetary 
compensation or free medical care to you in the event of a study-related injury.  
For questions about the study or research-related injury, contact Dr. Marat Fudim at 919-681-2549 
during regular business hours and at 919-970-8372 after hours and on weekends and holidays
WHAT ABOUT MY RIGHTS TO DECLINE PARTICIPATION OR WITHDRAW FROM THE 
STUDY?
You may choose not to be in the study, or, if you agree to be in the study, you may withdraw from the 
study at any time. If you withdraw from the study, no new data about you will be collected for study 
purposes unless the data concern an adverse event (a bad effect) related to the study.  If such an adverse 
event occurs, we may need to review your entire medical record.  
Your decision not to participate or to withdraw from the study will not involve any penalty or loss of 
benefits to which you are entitled, and will not affect your access to health care at Duke. If you do 
decide to withdraw, we ask that you contact Dr. Fudim in writing and let him know that you are 
withdrawing from the study.  His mailing address is PO box 17969, 27715 Durham.  No further action 
will be required on your part once you have withdrawn from the study.
DUHS IRB
IRB NUMBER: Pro00103788
IRB REFERENCE DATE: 05/13/2022
IRB EXPIRATION DATE: 05/21/2023


Consent To Participate In A Research Study
Splanchnic Nerve Blockade as Treatment of Chronic Heart 
Failure
Page 16 of 17                                                  Subject*Initials:______________
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
We will tell you about new information that may affect your health, welfare, or willingness to stay in 
this study.
Your doctor may decide to take you off this study if your condition gets worse, if you have serious side 
effects, or if your study doctor determines that it is no longer in your best interest to continue.  The 
sponsor or regulatory agencies may stop this study at any time without your consent. Reasons why this 
might occur include an unsafe drop in blood pressure, worsening symptoms, new infection, or any 
condition whereby participation in the study poses a risk to your health. If this occurs, you will be 
notified and your study doctor will discuss other options with you.
A description of this clinical trial will be available on http://www.ClinicalTrials.gov, as required by U.S. 
Law.  This Web site will not include information that can identify you.  At most, the Web site will 
include a summary of the results.  You can search this Web site at any time.
WHOM DO I CALL IF I HAVE QUESTIONS OR PROBLEMS?
For questions about the study or a research-related injury, or if you have problems, concerns, questions 
or suggestions about the research, contact Dr. Marat Fudim at 919-681-2549 during regular business 
hour,s and at 919-970-8372 after hours and on weekends and holidays.
For questions about your rights as a research participant, or to discuss problems, concerns or suggestions 
related to the research, or to obtain information or offer input about the research, contact the Duke 
University Health System Institutional Review Board (IRB) Office at (919) 668-5111.
DUHS IRB
IRB NUMBER: Pro00103788
IRB REFERENCE DATE: 05/13/2022
IRB EXPIRATION DATE: 05/21/2023


Consent To Participate In A Research Study
Splanchnic Nerve Blockade as Treatment of Chronic Heart 
Failure
Page 17 of 17
                                                  *
DUKE UNIVERSITY HEALTH SYSTEM
Form
M0345
STATEMENT OF CONSENT
"The purpose of this study, procedures to be followed, risks and benefits have been explained to me. I 
have been allowed to ask questions, and my questions have been answered to my satisfaction. I have 
been told whom to contact if I have questions, to discuss problems, concerns, or suggestions related to 
the research, or to obtain information or offer input about the research. I have read this consent form and 
agree to be in this study, with the understanding that I may withdraw at any time. I have been told that I 
will be given a signed and dated copy of this consent form."
__________________________________
_______________      ___________
Signature of Subject
Date
   Time
__________________________________
              _______________     ____________
Printed Name of Subject                      
     Date                     Time
__________________________________
_______________      ___________
Signature of Person Obtaining Consent 
 Date
   Time
__________________________________
              _______________     ____________
Printed Name of Person Obtaining Consent                      
Date                     Time
DUHS IRB
IRB NUMBER: Pro00103788
IRB REFERENCE DATE: 05/13/2022
IRB EXPIRATION DATE: 05/21/2023