Clinical trial NCT02669407
Conditions: Heart Failure
Sponsor: Duke University
Start date: 2017-01-01; Completion date: 2018-10-01
Enrollment: 14 participants; Allocation: NA; Intervention model: SINGLE_GROUP

Brief summary:
Patients admitted for acute heart failure and undergoing right heart catheterization will be enrolled in this study. Subjects will undergo catheterization of the heart to obtain central cardiac pressure and other cardiac hemodynamic parameters. Subsequently, the subject will undergo a regional nerve block of the splanchnic nerves. Patients will remain in the catheterization lab for the duration of anesthetic block and will be continuously hemodynamically monitored.

This study will be a prospective, uncontrolled clinical trial. The study will not be controlled as invasive monitoring of hemodynamics will be performed, allowing clear demonstration of a cause-effect relationship. The goal of the study is to provide proof of concept.

Detailed description:

Arms: arm 1: Regional nerve anesthesia of splanchnic nerve
Interventions: intervention 1: splanchnic nerve anesthesia with a local anesthetic intervention 2: regional nerve block with a local anesthetic (Lidocaine)
Intervention descriptions: intervention 1: regional nerve block of the splanchnic nerve intervention 2: None

Protocol documents:
Prot_SAP_000.pdf: 
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NCT02669407 
 
1.  Protocol Title:  
Splanchnic Nerve Block for Therapy of Acute Heart Failure (Splanchnic HF) 
 
2.  Purpose of the Study:  
Splanchnic vasoconstriction may contribute to decompensation of chronic heart 
failure 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. Therefore, 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 heart 
failure. 
 
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 increases urine output. 
3. We will determine whether splanchnic nerve blockade produces rapid 
improvement in creatinine clearance. 
 
3.  Background & Significance:  
Conventional wisdom dictates that heart failure (HF) exacerbations follow a 
period of fluid accumulation leading to volume overload. However, study of 
weight in HF shows that 54% of patients have an exacerbation without antecedent 
weight gain. Invasive monitoring of hemodynamics showed that central venous 
pressure rises in the weeks prior to decompensation despite no weight change in 
both systolic and diastolic heart failure. The leading theory for explaining this 
phenomenon of increased central venous pressure in the absence of change in 
total body water is that patients with heart failure (HF) have impaired ability to 
store blood in their splanchnic vascular compartment. In a healthy population, the 
splanchnic bed contains about 40% of the total blood volume, 80% of which is 
stored in capacitance veins, and serves as a buffer for the central vascular 
compartment. Fluid is normally mobilized from this compartment via increased 
sympathetic tone and circulating catecholamines in response to a variety of 
physiologic and pathologic stressors. Given the role that the splanchnic 
circulation plays in hemodynamic regulation, it is hypothesized that increased 
sympathetic tone in the splanchnic vasculature contributes to both acute and 
chronic heart failure decompensation by mobilizing fluid to the central 
vasculature (Fallick C, Circulation Heart Failure 2011).  
 
Animal models provide direct evidence of this pathophysiological effect. In 
healthy animals, splanchnic nerve stimulation shifts blood into the central 
compartment, increasing preload and cardiac output. In dogs with cardiac pacing 
induced systolic heart failure, splanchnic vascular capacitance was decreased 
(Ogilvie RI, circulation 1992). In these dogs, surgical transection of the 
splanchnic nerve, terminating sympathetic tone, results in decreased preload as 


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measured by systolic and diastolic filling pressures and increased compliance of 
the left ventricle (Figure A). In humans splanchnic nerve blocks are commonly 
used for pain control in patients with intractable visceral organ cancer pain. The 
nerve blocks are done temporarily using anesthetic agents or more commonly 
permanently using neurolytic agents. Interestingly, the most common “side-
effect” of this therapy includes transient orthostatic hypotension due an increase 
in splanchnic vascular storage capacity, which typically is prevented by 
aggressive pre-procedural hydration (Eisenberg E, Anesthesia and analgesia 
1995).  
 
 
 
 
  
 
Figure A: Preliminary data from one paced HF dog model with transection 
unilateral splanchnic nerve. A: Left ventricular end systolic (ESV) and diastolic 
(EDV) volume following nerve transection at time point zero in mL. Ped = left 
ventricular end-diastolic pressure in mmHg.  
Figure B: Pressure-volume recording in left ventricle in same animal. Blue curves 
are the baseline recordings and red indicate pressure-volume loops after nerve 
transection. Nerve transection caused flattening of the end-diastolic pressure-
volume relationship indicating higher compliance. Unpublished pilot data.  
A 
B


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In addition to the strong evidence supporting splanchnic nerve blockade as 
treatment of volume overload, it is possible it will also treat cardiorenal 
syndrome. The autonomic nervous system plays a critical role in the regulation of 
the kidney. Though this system is not fully understood, preclinical and clinical 
studies indicate the presence of a hepatorenal reflex that inhibits the renal function 
and causes fluid retention. This reflex has its origin in the portal vein and is 
stimulated by portal congestion. The splanchnic nerves represent the afferent and 
partially the efferent arm of the reflex arch. Inhibition of this reflex pathway in 
animals and a small human pilot study was shown to improve renal function and 
urine production. 
 
4.  Design & Procedures:  
This study will be a prospective, uncontrolled clinical trial. The study will not be 
controlled as invasive monitoring of hemodynamics will be performed, allowing 
clear demonstration of a cause-effect relationship. Furthermore, the goal of the 
study is to demonstrate proof of concept.  
 
This study aims to piggy-back on an elective right heart catheterization (+/- left 
heart catheterization) in patients admitted for acute decompensated heart failure 
The right (+/- left heart catheterization) will be part of the subject’s standard of 
clinical care (SOC). Subjects will undergo catheterization of the heart to obtain 
central cardiac pressure and other cardiac hemodynamic parameters found to be 
necessary by the primary team. This will occur in the cardiac catheterization lab. 
Once the SOC catheterization procedure is completed the subject will undergo, as 
part of this clinical study (CS), a regional nerve block (bilateral splanchnic 
nerves) while they are in the catheterization lab. This will be performed by an 
anesthesiologist experienced in splanchnic nerve blocks. Routinely, patient will 
remain in the catheterization lab for the duration of anesthetic block and will be 
continuously hemodynamically monitored. Also, prior to elective catheterization 
procedure and following splanchnic block patients will undergo a number of vital, 
laboratory and imaging tests, which will be in parts SOC or part of the CS (see 
Table of Assessments below).  
 
 


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Table of Assessments\ 
Required 
Assessment 
<5  Days 
before 
procedure 
Same day 
of 
procedure 
(<12h 
before 
procedure) 
Procedure 
(1-1.5h) 
Within 2 
hours 
after 
Procedure 
Day after 
procedure 
48 h after 
procedure 
6 Months 
after 
Procedure 
(±14 
days) 
Vitals 
(BP, HR, RR, 
SpO2) 
X 
(SOC) 
X 
(SOC) 
X 
(SOC) 
X 
(SOC) 
X 
(SOC) 
X 
(SOC) 
 
Weight 
X 
(SOC) 
X 
(SOC) 
 
X 
(SOC) 
X 
(SOC) 
X 
(SOC) 
 
Orthostatic 
vitals 
X 
(CS) 
 
 
X 
(CS) 
X 
(CS) 
 
 
Urine output 
(continuous 
recording) 
X 
(SOC) 
X 
(SOC+CS) 
X 
(SOC) 
X 
(CS) 
3 and 8 
hours 
post 
procedure 
X 
(SOC+CS) 
X 
(SOC+CS) 
 
Labs: BMP, 
pro-BNP, urine 
sodium, 
 
X 
(SOC/CS) 
 
X 
(CS) for 
pro-BNP 
and urine 
sodium 
X 
(SOC) for 
BMP 
X 
(BMP are 
SOC, no 
pro BNP 
needed) 
 
Labs 
(Angiotensin 
II), Plasma 
Metanephrines, 
Vasopressin, 
Plasma 
Catecholamines 
 
X 
(CS) 
 
X 
(CS) 
 
 
 
Dyspnea 
Questionnaire 
 
X 
(CS) 
X 
(CS) 
X 
(CS) 
X 
(CS) 
X 
(CS) 
 
Six minute walk 
test 
X 
(CS) 
 
 
X 
(CS) 
X 
(CS) 
X 
(CS) 
 
Impedance and 
lung fluid 
content 
measurement 
 
 
X 
(CS) 
X 
(CS) 
 
 
 
Positional 
Change: 
Bending Over  
 
X 
(CS) 
 
X 
(CS) 
 
 
 
Positional 
Change: Leg 
Raise 
 
 
X 
(CS) 
 
 
 
 
Heart rate 
variability 
X 
(CS) 
X 
(CS) 
X 
(CS) 
X 
(CS) 
X 
(CS) 
X 
(CS) 
 
Echocardiogram 
X 
(SOC) 
 
 
X 
(CS) 
 
 
 
Splanchnic 
nerve block 
 
 
X 
(CS) 
 
 
 
 
Phone Call** 
 
 
 
 
 
 
X 
(CS) 
*Plasma Metanephrines will be performed only if subject is on inotropes 
**Phone call will capture mortality status and number of subject admissions to the hospital since procedure 


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Following enrollment into the study the subject will undergo the following 
tests/measurements. A majority of the clinical testing occurs as part of routine clinical 
care and will be marked as SOC (like in the above table). Tests required only for the 
purpose of the study are marked with CS.  
 
Pre-procedure: Following information will be collected from the patient charts that will   
                         be done as standard of care (SOC). Study specific tests/recordings are  
                         also listed below: 
-  
If the subject is female and childbearing potential and has not had a 
pregnancy test since the arrival to the hospital, a blood pregnancy test will 
be done (CS). If positive the subject will be excluded from the study. 
-  
Subjects will have strict measurement of urine output (SOC). 
Additionally, subjects will be asked to void 3 hours prior to their 
procedure. They will be asked to void again immediately prior to the start 
of the procedure. A urine sample will be sent to the laboratory to check for 
the sodium concentration (CS). Subjects requiring a foley catheter will 
have measurements taken at comparable time intervals (SOC). 
- 
Recorded vitals including weight, BP, HR, RR, SPO2 on the day before 
procedure and within 1h before procedure (SOC) and record heart rate 
variability using a non-invasive wrist monitor for 5 minutes (CS).  
- 
Orthostatic vitals (5 minutes supine, 1+5 minutes sitting and 1+5 minutes 
standing) on the day before procedure and within 1h before procedure 
(CS) 
-  
Labs: Basic metabolic panel (BMP) (SOC), brain natriuretic peptide 
(BNP) (SOC/CS), plasma angiotensin II (CS), plasma arginine vasopressin 
(CS), plasma catecholamines.  Plasma metanephrines (CS) will be 
performed if subject is on inotropes. This will not require an extra lab 
draw. Total expected blood loss is <20ml.  
- 
Dyspnea questionnaire using a 7-point Likert scale and Visual Analog 
Scale (CS) 
- 
Six minute walk test (CS) 
- 
Echocardiogram during the admission and no longer than 5 days prior to 
study (SOC). If no up-to-date echocardiogram is present, a study related 
Echocardiogram will be obtained (CS). 
-  
If the patient is on diuretics medications the scheduling of the medication 
will be adjusted to minimize interference with the study intervention.  
1. If the patient is scheduled to be an early morning case in the 
catheterization laboratory then the morning dose of the diuretic 
(typically given at 8-9 am) will be given 3 hours after the 
procedure (CS).  
2. If the patient is scheduled to be an afternoon case in the 
laboratory then the morning dose will be given as planned or 
earlier to guarantee at least 5-6 hours between last diuretic dose 
and the procedure (CS).  
 


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Subjects who receive also an evening dose of diuretics will receive their 
second dose of diuretic as scheduled in the evening after the procedure 
(SOC). 
-   
Other medications can be continued, unless otherwise specified in the 
exclusion criteria. 
- 
Positional change of bending over to evaluate ‘bendopnea’ (shortness of 
breath symptoms with bending over).  
 
 
Procedure: 
 
1. Patients will undergo elective right (+/- left) heart catheterization in the Duke 
catheterization laboratory lab as ordered by the primary team. Central 
hemodynamics will be recorded (baseline, prior to nerve block) (SOC). The 
access site for the right heart catheterization will be radial, brachial or cervical 
(SOC) to allow a prone positioning of the patient for the splanchnic nerve 
block described in the next paragraph.   
 
If the patient’s hemodynamics do not show evidence of cardiac decompensation 
or provide any other concern for complications related to the splanchnic nerve 
block as determined by the study personnel, the splanchnic nerve block and 
associated monitoring will not be performed. The patient will be considered a 
screen failure. Any patient information and samples collected prior to this will be 
discarded/destroyed per institutional policies. Cardiac decompensation is defined 
as a wedge pressure <15mmHg (<12mmHg on inotrope) and greater than central 
venous. 
 
If invasive hemodynamics support decompensated heart failure the patient will 
proceed with the study procedure and monitoring outlined below. 
 
Prior to the nerve block being performed, the subject will perform a positional 
change of a leg raise to observe if any shortness of breath symptoms occur.  
 
Patient will further be monitored with:  
- 
Telemetry (SOC) 
- 
ClearSite/CheetahMedical/Sphygmocor/ReDS 
for 
continuous 
non-
invasive hemodynamic/lung fluid content recording (CS) 
 
- 
Continuous urine output (ml/hour) recording if foley is present (SOC) 
- 
A non-invasive wrist monitor to monitor the heart rate variability 
 
 
2. Bilateral splanchnic nerve block performed by an anesthesiologist (see images 
below) (CS). Following the right heart catheterization procedure the patient will 
be prone on the abdomen. Central venous access remains in place. Needle will be 
placed under fluoroscopic guidance in the posterior chest wall. Anesthetic 
solution (1% lidocaine with epinephrine) (1:200.000) will be injected (10-15 ml 
on each side). Patient will then be placed back on his/her back and central 


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hemodynamics are recorded again for the next 1-1.5 hours, approximately every 
15 minutes. The central venous catheter will be removed after the hemodynamic 
monitoring is completed in the catheterization laboratory. Unless the primary 
team requested the catheter to remain in place and the patient is moved to the 
intensive care unit.  
 
Following the block, the subject will repeat the positional change of a leg raise at 30, 60, 
and 90 minutes post-block to observe any changes in shortness of breath symptoms. 
 
 
Additional measurements include: 
-      
Orthostatic vitals will be obtained at the end of the hour while in the    
             catheterization lab (CS).  
- 
Dyspnea questionnaire (CS) 
- 
If medically indicated a Swan Ganz catheter will be left in place. This 
would enable continuous monitoring of central hemodynamics for the next 
24h (q4h) (SOC).  
 
 
 
 
Follow up procedures: 
 
Following right heart catheterization and lidocaine splanchnic nerve block the 
patient will be monitored on the floor/CCU for at least 48 hours following nerve 
block (SOC). 
 
- 
Continuous recording of urine output for 24 hours (SOC). They will then 
be asked to void again 3 and 8 hours after the placement of the nerve 
block and 24 hours after nerve block (CS). 
- 
Basic vitals (SOC) and orthostatic vitals (CS) within 24 hours after nerve 
block, and record heart rate variability using a non-invasive wrist monitor 
(CS). 


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- 
Repeat labs 12-24 hours after nerve block (next morning) [BUN (SOC), 
BMP (SOC) and pro-BNP (CS) 
-  
Labs: Angiotensin 2, plasma metanephrines (if on inotropes), plasma 
catecholamines, vasopressin and urine sodium will be collected 
immediately before and after the procedure 
- 
Dyspnea questionnaire at 12-24 hours after nerve block (CS) and again at 
48 hours 
- 
Six minute walk test (CS) within 24 hours after block and again at 48 
hours 
- 
Weight the next morning after nerve block (SOC) and at 48 hours. 
- 
Echocardiogram within 1-2 hours after nerve block (CS) 
- 
Positional change of bending over to evaluate ‘bendopnea’ (shortness of 
breath symptoms with bending over). 
 
Phone Call 
Subjects will be contacted by study team six months (± 14 days) following their nerve 
block procedure. The purpose of this call will be to obtain mortality status and 
document the number of inpatient admissions since the procedure.  
 
Blood samples processing:  
Some blood samples collected before and after the nerve block (plasma 
metanephrines, plasma catecholamines, angiotensin II and arginine vasopressin) 
will be processed (centrifuged) and stored at -70 degrees Fahrenheit before sent 
out to an external lab. Storage duration may vary between weeks to months. 
Samples will be stored in a research freezer located on the 7th floor of Duke North 
(cath lab research freezer). As part of the study, we will send blood for study-
related laboratory tests to the Mayo clinic and Inter Science Institute. These 
would 
include 
laboratory 
tests 
such 
as 
metanephrines, 
vasopressin, 
catecholamines, and angiotensin. 
  
Safety endpoints: 
- 
The duration of the anesthetic block is estimated for 1.5 hours. The subject 
will be monitored for up to 1.5 hours in the catheterization laboratory (acute 
safety). Chronic safety up to 48 hours post procedure. Hereby the patient will 
be observed clinically on the floor or CCU per standard clinical care routine. 
Further the subject’s medical chart will be observed for 6 months following 
study enrollment to evaluate for recurrent admissions for heart failure.  
 
 
 
Incidence of major side effects like: 
  
 
 
-  
Pneumothorax, possibly requiring a chest tube 
-  
Aortic puncture with retroperitoneal bleed or hematothorax 
-   
Spinal cord trauma with possibly paralysis 
 
Incidence of minor side effects like: 
 
-  
Orthostatic hypotension 
-  
Pain at puncture site and intercostal neuralgia 


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9
-  
Gastrointestinal 
dysmotility 
including 
diarrhea, 
constipation and abdominal cramping 
-  
Bleeding at puncture site 
 
Efficacy endpoints: 
 
The following efficacy endpoints will be evaluated: 
 
Primary:     -  Reduction in central venous pressure and/or pulmonary  
artery pressure (diastolic) and/or pulmonary capillary  
wedge pressure at 30-60 minutes after nerve block 
 
Secondary: -  Increase 
in 
cardiac 
output, 
improvement 
in 
echocardiographic 
parameters 
like 
ejection 
fraction 
(increase), central venous pressure (decrease), pulmonary 
artery systolic pressure (decrease), right ventricular 
diameter (decrease), left ventricular diameter (decrease)  
      -  Reduction in pro brain natriuretic peptide (pro-BNP) 
-  Increase in UOP (output measured in ml/hour) and renal 
function (BUN and creatinine) in the hours following the 
procedure. Follow up for 48hours 
-  Symptomatic improvement like a decrease in dyspnea 
(dyspnea questionnaire) and 6-minute walk test 
 
 
5.  Selection of Subjects: 
 
Subjects will be recruited from Duke University Medical Center. All potential 
study subjects are admitted for ADHF and are treated as inpatient on the regular 
floor or in the intensive care unit.  
 
The study will enroll subjects who meet the criteria as detailed below. Potentially 
eligible patients will be consented and entered into a screening process, which 
will include a chart review and physical examination. The primary enrollment 
target is up to 20 subjects (10 HF with preserved ejection fraction and 10 HF with 
reduced ejection fraction).  
 
Inclusion criteria:  
- 
Age 18-90 
- 
Established diagnosis of HFpEF or HFrEF 
- 
Admitted to DUMC for decompensated HF (NYHA stage 3-4, Class C-D), 
including patients on inotropic medication 
- 
Symptomatic with dyspnea with clinical, radiographic or echocardiographic signs 
of fluid overload 
- 
Planned for elective diagnostic right (+/- left) heart catheterization  
- 
On a stable HF drug regimen prior to admission 
- 
Anticipated hospital stay of at least 2 nights following catheterization procedure 


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- 
Preferably “diuretic resistant”. Urine output <50ml/hour in the 24 hours preceding 
enrollment into the study. 
 
 
Exclusion criteria:  
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 
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,  
- 
Recent acute MI or hemodynamic instability: 
- 
Acute MI (STEMI or Type I NSTEMI) within 7 days? 
- 
Evidence of progressive cardiogenic shock within 48 hours 
- 
Repeat systolic blood pressure <90mmHg or >180mmHg 
Certain forms of HF: 
- 
Restrictive cardiomyopathy 
- 
Constrictive pericarditis 
- 
Pericardial effusion with evidence of tamponade 
- 
Severe valvular stenosis  
Severe bleeding risk: 
- 
Known history of an increased bleeding risk 
- 
Thrombocytopenia (<50,000) 
Significant comorbidities: 
- 
End-stage renal disease CKD stage 5 due to primary renal pathology 
- 
Any form of preceding acute or chronic use of ultrafiltration or hemodialysis 
- 
History of thoracic spine surgery 
- 
Scoliosis of the thoracic spine 
- 
History of lung surgery or history of pneumothorax or chest tube placement 
during the current admission 
- 
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 pulmonary hypertension 
- 
History of abdominal organ transplant (liver, pancreases, small bowel, kidney) or 
splenectomy 
Pregnancy 
Procedure 
- 
Unable to tolerate procedure as determined by patient or investigator 


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-  Patient will be excluded if invasive hemodynamics on study date determine that 
the patient does not have elevated filling pressures. Following pressures/situations 
will exclude the patient: wedge pressure <15mmHg (<12mmHg on inotrope) and 
greater than the central venous pressure or patient determined by study personnel to 
be at risk for nerve block related complications.  
 
6.  Subject Recruitment & Compensation: 
Potential subjects will be identified via two potential pathways. Cardiology 
inpatient teams will be informed about the study and will be encouraged to notify 
the study team if a patient is planned for an elective right (+/-) left heart 
catheterization in the upcoming days. Subjects will also be identified by a daily 
review of the catheterization scheduling board, which identifies scheduled 
procedures for the given week. This way the study team would be able to identify 
subjects about whom they were not informed by the primary care taking team.  
 
Patients that were identified to be potential candidates for this study will be 
screened to evaluate for inclusion/exclusion criteria before approaching the 
patient for study 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. 
 
There will be no compensation for participation in this clinical study. 
 
7.  Consent Process  
 
Candidate subjects will be informed of the risks and benefits of participation of 
the study. They will be informed of the study process and demands. They will be 
given a copy of the informed consent document to review and afforded adequate 
time to do so. If the elective catheterization procedure (SOC) is scheduled for the 
upcoming day than the consent will need to be signed before midnight to allow 
enough time to obtain pre-procedural test as outlined above. 
 
Informed consent will be obtained prior to the right heart catheterization. Consent 
will be obtained by Study PI, Duke heart center study coordinators who are 
trained on the study and who have been trained on Informed Consent Process and 
other key personnel as designated by the PI. Consent will be obtained in the 
patient’s room or the catheterization laboratory holding area. Only after a member 
of the patients medical care team who is known to the patient approaches them 
about the study will the study team talk with the patient about this study. A 
subject is considered enrolled in this clinical study at the time at which the subject 
and investigator or authorized designee have personally signed and dated the 
Informed Consent Form. 
 
8.  Subject’s Capacity to Give Legally Effective Consent: 
 


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12 
Subject has to be able to understand the English language and understand the 
study process including all potential risk and benefits to the patient. Any subject 
where the study personnel or treatment team has cause for concern regarding the 
patient’s ability to understand the study process or follow the consent process 
capacity, will be excluded from the study. 
 
9.  Study Interventions: 
 
-  
Regional nerve block under fluoroscopic guidance 
-  
Lab draws 
-  
Vital signs 
- 
Orthostatic vital signs 
-  
6-minute walk test 
- 
Non-invasive imaging with ultrasound 
-  
Optional: Foley placement 
 
10. Risk/Benefit Assessment: 
 
 
Procedural risks of splanchnic nerve blocks have been extensively studied. Risks 
associated with this anesthetic nerve block are uncommon. 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 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 heart failure, which is a new indication. 
The splanchnic nerve block has not been studied in the setting of this disease. 
While we don’t expect unexpected side effects other than stated above, 
unexpected side effects cannot be excluded. For safety purposes patients enrolled 
in this study will remain hospitalized for at least 48 hours (part of enrollment 
criteria). This way they will be closely monitored while admitted on a cardiology 
floor/unit.  
 
 
 
Anticipated benefits to the patient 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. 
 


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13 
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, the benefit provided by the brief 
episode of decongestion can provide lasting symptomatic improvement. Our 
intervention serves an additional diagnostic purpose by confirming an increased 
sympathetic tone in the abdominal innervation and could prompt the treatment 
team to adjust medical therapy to address the increased sympathetic tone and 
possible benefit on increased splanchnic capacitance.  
 
11. Costs to the Subject: 
 
The study will be at no additional cost to the patient on top of his regular 
hospitalization for heart failure and elective catheterization.  
 
 
12. Data Analysis & Statistical Considerations: 
 
Descriptive statistics of continuous outcomes will include sample size, mean, 
median, standard deviation, minimum and maximum. For categorical outcomes, 
the number and percentage of subjects in each category will be presented. 
Statistical comparisons will be made using t-tests for continuous outcomes and 
chi square or Fisher’s exact test (depending on overall event rates) for categorical 
outcomes. Paired t-tests will be used to compare changes from baseline to post-
intervention. All statistical analyses will be performed using SAS for Windows 
(version 8.2 or higher) or other widely accepted statistical or graphical software. 
Patient data listings and tabular and graphical presentations of results will be 
provided. Unless otherwise specified, a two-sided 0.05 level of significance will 
be used to declare change in pre- and post-procedure variables different.  
 
For power analysis, our primary endpoint is decreased in central venous pressure 
following nerve blockade. Based on preliminary animal experiments, we 
anticipate a reduction of CVP of 25%. For a sample size of 16, If the true 
difference in the experimental and control means is 25%, we will be able to reject 
the null hypothesis that the population means of the experimental and control 
groups are equal with probability (power) .90. The Type I error probability 
associated with this test of this null hypothesis is 0.05. 
 
There is no direct measure of technical success following attempted block of the 
splanchnic nerves.  The location of the splanchnic nerves is estimated biased on 
human anatomy dissections and established nerve block protocols used by the 
anesthesiology department. 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. 
 
13. Data & Safety Monitoring:  


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14 
 
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, patient’s electronic medical data will be clinically screened for any 
traumatic complications from the nerve block for the first 24 hours post-
procedure.  
 
Unanticipated adverse events, which are severe (listed above), will be reported to 
the IRB within 24 hours. Any other adverse event will be reported to IRB within 
10 working days or per IRB requirements. The Principal Investigator will also 
provide an annual report of any side effects or problems to the IRB during the 
study renewal process.   
 
Following discharge, the subject’s medical record will be monitored for 
readmission to the Duke hospital for heart failure.  
 
The study related results will be reported to the Duke Translational Research 
Institute. These would include laboratory tests, imaging studies and clinical tests 
like 6 minute walk test and dyspnea questionnaire.  
 
14. Privacy, Data Storage & Confidentiality – see Section 12 of the e-IRB 
submission form and complete the questions in that section.   
 
1. Data will be obtained by approved study personnel. An enrollment log will also 
be maintained in Excel Spreadsheet on the Heart Center’s S:drive. The subject ID 
will also be stored on the folder to track patient enrollment and collection of data. 
Only de-identified data will be available for statistical analysis. All patient 
identifiers will be removed for database storage, statistical analysis and data 
reporting. This data will be stored on a study specific folder on the Duke server 
behind the Duke firewall.  The subject ID code will be destroyed after data 
analysis is completed. Protected health information will not be used for any other 
purposes than those described in this protocol without obtaining further IRB 
approval.  This information will be used for research purposes only and patients 
will never be contacted regarding information obtained through chart review. A 
designated statistician from the DCRI will provide support with statistical 
analysis. 
 
The adequacy of the Research Data Security Plan (RDSP) will be evaluated and 
approved by the Cardiology CRU prior to study conduct. 
 
Any publications or presentations that result from this research will not identify 
any subjects individually, and will present data in aggregate form only. 
  
 
Gathered data will be stored for at least 6 years.