Endovascular Denervation Improves Limb Ischemia in Patients With Peripheral Artery Disease (ED-PAD)
Phase: NA
Conditions: PAD
Sponsor: Zhongda Hospital

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Endovascular Denervation Improves Limb Ischemia in Patients with Peripheral 
Artery Disease 
 
Principal Investigator: Gaojun Teng 
                  Zhongda Hospital affiliated to Southeast University 
 
Protocol Version: A/2, 28 May 2018 
 
Study purpose 
To evaluate the safety and preliminary efficacy of endovascular denervation (EDN) for 
the treatment of patients with peripheral artery disease (PAD). 
 
Study design 
This study was a prospective, single-center, open-labeled, randomized controlled trial 
designed to evaluate the safety and efficacy of ER combined with EDN for treating 
lower limb PAD. Patients who meet the following criteria were randomly assigned to 
the group of ER alone or ER combined with EDN. Subjects in the control group were 
treated with ER including PTA, DCB, and/or stenting, and patients in the ER+EDN 
group were treated with EDN from distal iliac artery to proximal superficial femoral 
artery before ER.  
 
 

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Sample size 
1 site, 20 subjects. 
 
The inclusion criteria:  
(a) eligible subjects aged 18-75 years; 
(b) clinically confirmed PAD in the lower extremities; 
(c) Rutherford category II-VI.  
 
The exclusion criteria:  
(a) thrombolytic therapy performed within 30 days; 
(b) patients who had undergone vascular bypass surgery before this study; 
(c) allergy or contraindication of antiplatelet drugs, anticoagulants, thrombolytic drugs 
and contrast agents,; 
(d) 
patients 
with 
obvious 
bleeding 
tendency, 
coagulation 
dysfunction, 
hypercoagulability and blood system diseases; 
(e) serious liver and kidney diseases; 
(f) history of hemorrhagic stroke within last month or ischemic stroke or transient 
ischemic attack within 2 weeks; 
(g) pacemaker implants; 
(h) patients who are pregnant, breast-feeding or planning pregnancy; 
(i) expected survival < 24 months. 
 

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The primary endpoint was the improvement of ABI at 6-month post-procedure.  
The secondary endpoints included transcutaneous oxygen pressure (TcPO2), 
Rutherford category, numerical rating scale (NRS) score and safety.  
Safety endpoints was the occurrence of trial-related adverse events that occurred 
during this trial. Possible adverse or serious adverse events during surgery: femoral 
artery stenosis, femoral artery dissection, thromboembolism (stroke or TIA), pus, 
hematoma at the puncture site, arteriovenous fistula requiring blood transfusion and/or 
surgical treatment, and other "serious" adverse events during the trial. 
 
Statistics and Analysis  
All continuous data are presented as mean ± standard deviation (SD) or median with 
interquartile range. Categorical data are reported as numbers and percentages. Paired t-
test and Wilcoxon signed-rank test were used to compare parameters at baseline and the 
6-month follow-up. Student's t-test and Mann-Whitney U test were used to compare 
parameters between the two groups. When multiple follow-ups were analyzed, one-way 
repeated-measures ANOVA along with Bonferroni correction were used. Differences in 
categorical data between the two groups were analyzed using the chi-square test. P < 
0.05 was considered statistically significant. All statistical analyses were performed 
using SPSS (version 22.0, SPSS, Chicago, USA) and GraphPad Prism 8 (GraphPad 
Software, San Diego, California). 
 

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Study process 
Visit 1 (Subject Screening):  
During this visit, cases are selected. Collect demographic data of patients, record 
patients' past medical history and medication, record vital signs, and collect patients' 
general physical examination. Blood pressure assessment, Rutherford scale, Wagner 
scale of diabetic foot ulcer, pain NRS score, painless walking distance PFWD 
examination, 
electrocardiogram 
examination, 
anklebrachial 
index 
(ABI), 
transcutaneous partial pressure of oxygen (TcPO2), foot sensory threshold 
measurement, thromboelastography (TEG), VUS microcirculation detection, and target 
vessels were performed Color Doppler ultrasound and computed tomography 
angiography (CTA) were used to sign informed consent for patients who met the initial 
criteria. Blood biochemical tests were performed, including blood routine, liver 
function, kidney function, urine routine, blood lipids, coagulation function, blood 
electrolytes, catecholamines, glycosylated hemoglobin, angiotensin II, aldosterone, 
insulin, glucagon, homocysteine, blood glucose. 
 
Visit 2 (0 day, Baseline): 
The visit was considered to determine the patient's admission/procedure date. For 
patients meeting the requirements, balloon catheter pre-dilation after DSA of the artery 
at the affected site, femoral popliteal artery stent implantation, balloon catheter post-
dilation, and then arterial and nerve radiofrequency ablation were performed. 
 

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Visit 3 (7±2 days): 
The visit was considered 7±2 days after surgery. Blood routine examination, renal 
function, liver function, blood electrolyte, catecholamine, glycated hemoglobin, 
angiotensin II, aldosterone, insulin, glucagon, homocysteine, blood pressure 
assessment, blood glucose, ankle-brachial index (ABI), transcutaneous partial pressure 
of oxygen (TcPO2), foot sensory threshold measurement, VUS microcirculation 
detection, pain NRS score were performed. Drug use and complications. 
 
Visit 4 (1month±7 days): 
The visit was considered 1 month ±7 days after surgery. Blood routine examination, 
renal function, liver function, coagulation function, blood lipid, catecholamine, 
glycated hemoglobin, angiotensin II, aldosterone, insulin, glucagon, homocysteine, 
blood pressure assessment, blood glucose, ankle-brachial index (ABI), transcutaneous 
partial pressure of oxygen (TcPO2), foot sensory threshold measurement, VUS 
microcirculation detection, Ruthe were performed rford scale, Wagner scale of diabetic 
foot ulcer, pain NRS score, painless walking distance PFWD examination, drug use and 
complications. 
 
Visit 5 (3 months±7 days): 
The visit was considered 3 months ±7 days after surgery. Blood routine examination, 
renal function, liver function, coagulation function, blood lipid, blood electrolyte, 
catecholamine, glycosylated hemoglobin, angiotensin II, aldosterone, insulin, glucagon, 

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homocysteine, blood pressure assessment, blood glucose, ankle-brachial index (ABI), 
transcutaneous partial pressure of oxygen (TcPO2), foot sensory threshold 
measurement, VUS microcirculation detection, blood pressure assessment, blood 
pressure assessment, blood pressure assessment. Rutherford scale, Wagner scale of 
diabetic foot ulcer, pain NRS score, painless walking distance PFWD examination, drug 
use and complications. 
 
Visit 6 (6 months±7 days): 
The visit was considered 6 months ±7 days after surgery. Blood routine examination, 
renal function, liver function, coagulation function, blood lipid, blood electrolyte, 
catecholamine, glycosylated hemoglobin, angiotensin II, aldosterone, insulin, glucagon, 
homocysteine, blood pressure assessment, blood glucose, ankle-brachial index (ABI), 
transcutaneous partial pressure of oxygen (TcPO2), foot sensory threshold 
measurement, VUS microcirculation detection, blood pressure assessment, blood 
pressure assessment, blood pressure assessment. Rutherford scale, Wagner scale of 
diabetic foot ulcer, pain NRS score, painless walking distance PFWD examination, 
color Doppler ultrasound, computed tomography angiography (CTA), drug use and 
complications. 
 
Adverse event observation 
All adverse events were observed, and detailed description of symptoms, date of 
occurrence, date of termination, relationship between degree and device, course of 

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treatment, and outcome were recorded. If fatal, disabling, teratogenic and other serious 
adverse events occur, regardless of whether they are related to the trial, emergency 
measures should be taken immediately to protect the interests of patients, and the main 
research unit, the ethics committee, the sponsor and the State Food and Drug 
Administration should be reported within 24 hours after being informed.