ARTISAN: iCAST™ RX De Novo Stent Placement for the Treatment of Atherosclerotic Renal Artery Stenosis in Patients With Resistant Hypertension
Phase: NA
Conditions: Renal Artery Stenosis, Hypertension, Renovascular
Sponsor: Atrium Medical Corporation

 
 
 
 
 
 
ARTISAN 
iCAST™ RX De Novo Stent Placement for the Treatment of  
Atherosclerotic Renal Artery Stenosis in Patients  
with Resistant Hypertension  
 
 
 
 
 
 
TRIAL SPONSOR 
 
Atrium Medical Corporation 
5 Wentworth Drive 
Hudson, NH, 03051 
U.S.A 
Phone: 603-880-1433 
Fax: 603-386-6501 
 
 
 
 
 
 
Protocol No: iCAST™ RX-ARAS-001 
Original Protocol: 22Nov11  
Amendment #1: 15Jul13 
 
 
 
 
Confidentiality Statement 
The information contained herein is confidential and the proprietary property of Atrium Medical 
Corporation and any unauthorized use or disclosure of such information without the prior written 
authorization of Atrium Medical is expressly prohibited. 
 

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iCAST™ RX-ARAS-001 
PROTOCOL SUMMARY 
 
 
TRIAL TITLE 
 
ARTISAN: iCAST™ RX De Novo Stent Placement for the 
Treatment of Atherosclerotic Renal Artery Stenosis in Patients 
with Resistant Hypertension  
OBJECTIVE 
 
The primary objective of the ARTISAN trial is to evaluate the 
safety and efficacy of the iCAST™ RX Stent System for the 
treatment of subjects with resistant hypertension associated with 
de novo atherosclerotic renal artery disease.  
PRIMARY ENDPOINTS 
 
Functional Endpoint: Assessment of primary patency rate at 9-
months, defined as continuous patency without the occurrence of 
a total occlusion of the original lesion, without a re-intervention 
to treat a partial or total occlusion of the stented segment, or 
bypass of the stented segment due to clinically-driven restenosis 
or occlusion.  
 
Clinical Endpoint: Improvement in systolic blood pressure 
(SBP) at 9-months as compared to baseline systolic blood 
pressure. 
SECONDARY 
ENDPOINTS 
 
1. The occurrence of procedure-related Major Adverse Events 
(MAE) reported as percentage of subjects with MAE, at 30-
days, 9-months, 12-months, 24-months, and 36-months. 
Inclusive of: 
a. Procedure- or device-related occurrence of death 
b. Q-Wave Myocardial Infarction (MI) 
c. Clinically driven target lesion revascularization 
(TLR) 
d. Significant embolic events  
i. Defined as unanticipated kidney/bowel 
infarct clinically driven by symptoms of 
abdominal or back pain and confirmed 
with CT scan or open surgery, lower 
extremity ulceration or gangrene, or 
kidney failure after 30-days, 9-months, 
12-months, 24-months, and 36-months. 
 
2. Technical success defined as successful delivery and 
deployment of the iCAST™ RX Stent System with ≤ 30% 

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iCAST™ RX-ARAS-001 
residual angiographic stenosis after covered stent deployment 
(including post-dilatation) assessed via quantitative vascular 
analysis (QVA) by an independent core laboratory.  
 
3. Procedural success defined as technical success without the 
occurrence of MAE prior to hospital discharge. 
 
4. TLR measured as the proportion of subjects that require a 
clinically-driven reintervention of the target lesion through 9-
months.  
a. A clinically-driven TLR is defined as a TLR 
(percutaneous balloon angioplasty (PTA), bare 
metal stent or repeat covered stent deployment, or 
surgical bypass) due to documented recurrent 
hypertension from 30-days post-procedure level 
and/or deterioration in renal function from 
baseline value, associated with angiographic core 
laboratory adjudication of a ≥ 60% diameter 
covered stent restenosis.  
 
5. Rate of incidental TLR defined as rate of TLRs not meeting 
the definition of a clinically driven TLR.  
 
6. Improved SBP control assessed at 30-days, 9-months, 12-
months, 24-months, and 36-months.  
 
7. Secondary patency rate at 9-months after a clinically-driven 
TLR which restores patency after total occlusion. 
 
8. Change in number and dosage of anti-hypertensive 
medications as compared to baseline. 
 
9. Renal function compared to baseline as measured by 
estimated glomerular filtration rate (eGFR) at 30-days and 9-
months. 
TRIAL DESIGN 
 
This is a prospective, single-arm, multicenter clinical trial that 
will take place at up to 25 US/OUS sites. Primary endpoints 
have been determined to show the safety, effectiveness, and 
clinical outcomes of the iCAST™ RX Stent System. Safety and 
effectiveness will be evaluated based on the primary patency rate 
at 9-months on a per lesion basis evaluated against a 
performance goal of published studies with bare-metal stents. 
The primary clinical endpoint will assess the improvement in 
SBP at 9-months as compared to baseline SBP.  

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iCAST™ RX-ARAS-001 
 
Eligible 
subjects 
will 
undergo 
a 
two-week 
Medical 
Documentation 
Screening 
period 
to 
confirm 
resistant 
hypertension (SBP ≥ 155mmHg) while on maximum tolerable 
doses of ≥ three anti-hypertensive medications from at least 
three classes of drugs, one of which must be a diuretic.  
 
There must be documented clinical evidence to support 
likelihood of angiographic findings > 80% whether it is Duplex 
Ultrasound (DUS), Computed Tomography angiogram (CTa), 
Magnetic Resonance angiogram (MRa) or other medical 
evidence. After meeting screening and clinical eligibility criteria, 
subjects will undergo a baseline assessment for angiographic 
eligibility. After angiographic documentation of a ≥ 80% 
diameter renal artery stenosis or Fraction Flow Reserve (FFR) < 
0.8 is confirmed, the subject may be enrolled in the trial by 
placement of the investigational device.  
 
The 9-month visit will include a follow-up DUS of the target 
renal artery. If the DUS is non-diagnostic due to an imaging 
quality problem, such as overlying bowel gas or body habitus, a 
second DUS may be attempted. If the DUS is indicative of ≥ 
60% stenosis as determined by the core laboratory, or the second 
DUS remains non-diagnostic, a contrast angiogram will be used 
to assess the degree of restenosis of the covered stent(s).  
 
Clinical follow-up visits will be required for all enrolled subjects 
at 30-days, 9-months, 12-months, 24-months, and 36-months.  A 
6-month and 18-month visit will occur via telephone to collect 
medication usage and Adverse Events (AEs) only.  The 36-
month clinic office visit will be required as the final safety visit.  
SUBJECT  
POPULATION 
 
Subjects who are candidates for a renal artery revascularization 
with ≥ 80% visual stenosis and have resistant hypertension with 
≥ 155mmHg while on ≥ 3 anti-hypertensive medications from at 
least 3 classes of drugs, one of which must be a diuretic. 
 
NUMBER OF SUBJECTS 
 
 
Up to 138 subjects will be enrolled in this trial. 
 
ESTIMATED TRIAL  
DURATION 
 
The trial duration is projected for 60 months. 

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ESTIMATED SUBJECT 
DURATION 
 
Each subject is expected to be enrolled and followed for a total 
of 36 months. 
STATISTICAL 
METHODS 
 
The sample size has been chosen to provide an adequate number 
of subjects to confirm the safety and efficacy of the iCAST™ 
RX Stent System. The co-primary endpoints of primary patency 
and reduction in SBP are powered at 87% and 92%, 
respectively, in order to maintain the overall trial power at 80% 
to meet both endpoints with a sample size of up to 138 subjects. 
 
 
 
 
 
 
CO-PRINCIPAL 
INVESTIGATORS 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
CONTRACT RESEARCH 
ORGANIZATION 
(MONITORING, DATA 
MANAGEMENT, DSMB, 
AND CEC) 
 
 
 
 
 
 
 
VASCULAR 
ULTRASOUND CORE 
LABORATORY 
 
 
 
 
 
 

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iCAST™ RX-ARAS-001 
ANGIOGRAPHIC CORE 
LABORATORY 
 
 
 
 
 
 
 
MEDICAL MONITOR 
AND SAFETY 
 
 
 
 
 
 
ELECTRONIC DATA 
CAPTURE 
 
 
 
 
 
 
 
SPONSOR 
 
Atrium Medical Corporation 
5 Wentworth Drive 
Hudson, NH 03051 
Phone: 603-880-1433 
Fax: 603-821-1420 
 
 
 
 

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iCAST™ RX-ARAS-001 
INVESTIGATOR PROTOCOL APPROVAL PAGE 
 
TRIAL TITLE: 
ARTISAN: iCAST™ RX De Novo Stent Placement for the 
Treatment of Atherosclerotic Renal Artery Stenosis in 
Patients with Resistant Hypertension 
INVESTIGATIONAL 
DEVICE: 
iCAST™ RX Stent System 
PROTOCOL VERSION: 
Amendment #1: 15Jul13 
PROTOCOL DATE: 
 
July 15, 2013 
SPONSOR: 
Atrium Medical Corporation 
 
Investigator’s Responsibility 
 
Prior to participation in the ARTISAN Trial, as the Investigator I understand that I must obtain 
written approval from my Institutional Review Board (IRB)/Ethics Committee (EC). This 
approval must include my name and I must send a copy to Atrium or its designated Contract 
Research Organization (CRO) along with the IRB/EC approved Informed Consent form (ICF) 
prior to any subject enrollment at my investigational site.   
  
As the Investigator, I must also: 
1. Conduct the trial in accordance with the trial protocol, the signed Clinical Investigation 
Agreement, Good Clinical Practice (GCP), and ensure that all study personnel are 
appropriately trained prior to any data collection. 
2. Ensure that the study is not commenced until IRB/EC approvals have been obtained. 
3. Ensure that written informed consent is obtained from each subject prior to any data 
collection. 
4. Provide all required data and reports and agree to source document verification of study 
data with patient’s medical records by Atrium or its designated CRO. 
5. Allow Atrium personnel or its designated CRO, to inspect and copy any documents 
pertaining to this clinical investigation. 
 
Investigator Signature  
 
I have read and understand the contents of the ARTISAN protocol and agree to abide by the 
requirements set forth in this document.  
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Investigator Name (print) 
 
 
 
Investigative Site (print) 
 
 
 
 
 
 
 
 
 
 
 
 
 
  
Investigator Signature  
 
 
  
Date 
 
 

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TABLE OF CONTENTS 
 
1.0 
BACKGROUND ................................................................................................. 11 
1.1 INVESTIGATIONAL DEVICE .......................................................................................................... 13 
1.2 INDICATION FOR USE .................................................................................................................... 14 
 
2.0 
TRIAL OBJECTIVES........................................................................................ 14 
2.1 RATIONALE ...................................................................................................................................... 14 
2.2 CO-PRIMARY ENDPOINTS ............................................................................................................. 17 
2.3 SECONDARY ENDPOINTS .............................................................................................................. 17 
 
3.0 
TRIAL DESIGN AND POPULATION ............................................................ 18 
3.1 DETERMINATION OF TRIAL ELIGIBILITY ................................................................................. 19 
3.2 INCLUSION CRITERIA .................................................................................................................... 19 
3.3 EXCLUSION CRITERIA ................................................................................................................... 20 
3.4 SUBJECT SCREENING ..................................................................................................................... 22 
3.5 SUBJECT ENROLLMENT ................................................................................................................ 25 
3.6 SUBJECT DISCONTINUATION ....................................................................................................... 25 
3.7 SUBJECT WITHDRAWAL ............................................................................................................... 25 
3.8 EARLY TERMINATION OF THE TRIAL ........................................................................................ 25 
 
4.0 
PROCEDURES AND ASSESSMENTS ............................................................ 26 
4.1 SCREENING PROCEDURES ............................................................................................................ 27 
4.2 PRIOR TO THE PROCEDURE .......................................................................................................... 28 
4.3 STENT IMPLANTATION .................................................................................................................. 28 
4.4 IMMEDIATE POST-PROCEDURE ................................................................................................... 28 
4.5 POST PROCEDURE FOLLOW-UP EVALUATIONS ...................................................................... 29 
4.6 CONCOMITANT MEDICATIONS ................................................................................................... 31 
 
5.0 
STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN ................... 32 
5.1 ASSUMPTION OF PRIMARY ENDPOINT RATE .......................................................................... 32 
5.2 SAMPLE SIZE .................................................................................................................................... 33 
5.3 ENDPOINT ANAYLSIS AND REPORTING OF RESULTS ........................................................... 35 
 
6.0 
ADVERSE EVENTS, SERIOUS ADVERSE EVENTS, AND  UNEXPECTED 
DEVICE EFFECTS ............................................................................................ 38 
6.1 DEFINITIONS .................................................................................................................................... 38 
6.2 DEVICE FAILURES, MALFUNCTIONS AND NEAR INCIDENTS .............................................. 39 
6.3 DOCUMENTATION .......................................................................................................................... 40 
6.4 EXPEDITED REPORTING OF SAEs AND UADEs ......................................................................... 41 
 
7.0 
TRIAL COMMITTEES ..................................................................................... 42 
7.1 DATA SAFETY MONITIORING BOARD (DSMB) ........................................................................ 42 
7.2 CLINICAL EVENTS COMMITTEE (CEC) ...................................................................................... 42 
 
8.0 
INVESTIGATOR RESPONSIBILITIES ......................................................... 42 
8.1 TRAINING .......................................................................................................................................... 42 
8.2 PROTOCOLS AND AMENDMENTS ............................................................................................... 43 
8.3 INFORMED CONSENT ..................................................................................................................... 43 
8.4 SOURCE DOCUMENTATION REQUIREMENTS .......................................................................... 43 
8.5 PROTOCOL DEVIATIONS ............................................................................................................... 44 
8.6 DEVICE ACCOUNTABILITY .......................................................................................................... 44 
8.7 MONITORING ................................................................................................................................... 45 

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8.8 AUDITS .............................................................................................................................................. 45 
8.9 RECORD RETENTION ...................................................................................................................... 46 
8.10 PUBLICATION POLICIES ................................................................................................................ 46 
 
9.0 
ROLE OF TRIAL SPONSOR ........................................................................... 46 
9.1 GENERAL DUTIES ........................................................................................................................... 46 
9.2 CRITERIA FOR SUSPENDING/TERMINATING AN INVESTIGATIONAL SITE ....................... 47 
 
10.0 
SUBJECT CONFIDENTIALITY ..................................................................... 47 
 
11.0 
RISKS TO SUBJECTS....................................................................................... 48 
11.1 HUMAN SUBJECTS INVOLVEMENT AND CHARACTERISTICS ............................................. 48 
11.2 POTENTIAL RISKS ........................................................................................................................... 48 
 
LIST OF APPENDICES 
APPENDIX 1: LIST OF ABBREVIATIONS ............................................................................................... 50 
APPENDIX 2: DEFINITIONS ...................................................................................................................... 51 
APPENDIX 3: METHODOLOGY FOR OFFICE-BASED BP MEASUREMENT ..................................... 57 
APPENDIX 4: SCHEDULE OF EVENTS ................................................................................................... 58 
APPENDIX 5: REFERENCES ..................................................................................................................... 59 
 
LIST OF IN-TEXT FIGURES 
FIGURE 1: MEDICAL DOCUMENTATION SCREENING PERIOD FLOW DIAGRAM   ..................... 24 
FIGURE 2: TRIAL FLOW DIAGRAM ........................................................................................................ 26 
 
LIST OF IN-TEXT TABLES 
TABLE 1: ICAST™ RX STENT SIZES ...................................................................................................... 14 
TABLE 2: CONCOMITANT MEDICATIONS ........................................................................................... 31 
TABLE 3: DERIVATION OF PATENCY PERFORMANCE GOAL ......................................................... 34 
TABLE 4: DERIVATION OF TLR PERFORMANCE GOAL .................................................................... 37 
TABLE 5: ANTICIPATED AES .................................................................................................................. 39 
TABLE 6: POTENTIAL AES RELATED TO STENT PLACEMENT ....................................................... 49 
 
 
 
 
 
 
 
 
 

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1.0 
BACKGROUND  
 
Atherosclerotic renal artery stenosis (ARAS) is the most common cause of renal artery stenosis 
(RAS) in the adult population.(1) ARAS may result in progressive renal impairment, renovascular 
hypertension, and/or cardiac disturbance syndromes. As the disease progresses, the resulting 
luminal narrowing decreases blood flow to the kidney, which, in turn, is often accompanied by a 
reduction in kidney function as well as hypertension triggered by activation of the renin-
angiotensin axis. If left untreated, ARAS may progress to renal failure.(2) 
 
The identification and management of patients with suboptimal control of hypertension and 
coexistent atherosclerotic renal artery stenosis is both challenging and controversial.(3, 4) Current 
ACC/AHA Peripheral Arterial Disease Guidelines identify renal artery stent deployment as a 
revascularization strategy in patients with hypertension resistant to optimal medical 
management.(5) However, a contemporary literature review suggested that there is no data 
supporting a revascularization strategy over optimal antihypertensive medical therapy.(6) Indeed, 
several single-arm prospective trials sponsored by commercial device manufacturers, while 
establishing the procedural safety of renal artery stent deployment after failed/suboptimal 
balloon angioplasty, were unable to demonstrate a predictable and durable reduction in blood 
pressure.(7, 8) 
 
More than 50% of subjects with uncontrolled hypertension unresponsive to traditional medical 
therapy may have significant ARAS and are considered candidates for surgical revascularization 
or percutaneous intervention for the resolution or stabilization of hypertension and renal 
dysfunction. Surgical revascularization has proven to be an effective treatment with acceptable 
long-term patency rates but is hampered by significant morbidity and mortality.(2) Percutaneous 
transluminal renal angioplasty (PTRA) has been successful in reducing morbidity and mortality 
compared to surgical revascularization but has poor technical success due to high rates of elastic 
recoil and dissection for typical ostial lesions, as well as high restenosis rates.  Primary stenting 
of atherosclerotic ostial lesions in the renal artery has thus become the preferred method of 
treatment due to higher success rates compared to surgical revascularization.(2) 
 
To date, there have been no pivotal clinical trials of blood pressure control or of safety, for newer 
generation stents in patients with resistant hypertension associated with ARAS. Previously 
published industry-sponsored trials have not focused on improvement of hypertension control as 
a primary endpoint.(9) The Cardiovascular Outcomes of Renal Artery Lesions (CORAL) trial(10), 
a National Institutes of Health (NIH) sponsored, prospective randomized controlled trial of 
optimal medical therapy compared to optimal medical therapy and renal artery stent deployment, 
will define the potential impact of renal artery stenting on rates of cardiovascular related 
morbidity and mortality, progression to renal replacement therapy and blood pressure control 
over five years of follow-up. However, the final analysis of this 1,050 cohort trial is not 
anticipated until after 2011. In the interim, clinical trials designed to establish the safety of new 

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renal stent designs and their effectiveness in improving blood pressure control are needed. In 
order to facilitate the initiation and completion of single-armed prospective trials investigating 
the safety and effectiveness of balloon-expandable stents to treat hypertensive patients with 
ARAS, physicians (VIVA) have used modern clinically relevant data and statistical modeling to 
develop blood pressure and procedural safety performance goals to be used as a comparator in 
some single-armed prospective trials.(2) 
 
Although a trend toward a favorable restenosis rate has been noted with the use of stents, 
as compared with the with balloon angioplasty alone,(11, 6) restenosis remains the main concern 
after PTRA stenting. Restenosis often results in symptom recurrence and may progress to 
occlusion and kidney loss. Thus, early restenosis detection is important to allow for effective 
secondary intervention; DUS is emerging as a screening modality for RAS.(12,13, 14) Although the 
value of DUS in RAS screening is well established, its role in assessing the hemodynamic 
outcome of percutaneous intervention and routine follow-up after successful intervention has not 
been well evaluated.(15) 
 
A number of recognized conditions can limit the accuracy of intrarenal DUS in RAS evaluation, 
such as multiple (more than two) renal arteries or only mild to moderate stenosis.(13) Patients who 
are young or have highly compliant arteries may have an absent early systolic peak, especially 
when distal interlobar arteries are sampled, which may yield false-positive results.(16) Conversely, 
noncompliant vessels may not display the parvus-tardus response and may result in false-
negative results.(17) Several extraneous factors may also affect the accuracy of intrarenal DUS 
including valvular heart disease, left ventricular contractility disorders, and the effect of 
vasoactive drugs.(15) 
 
Clinical follow-up, which has traditionally been used in large series of percutaneous and surgical 
renal artery revascularizations, may not enable detection of asymptomatic restenosis before it 
becomes symptomatic or progresses to kidney loss. Magnetic resonance angiography (MRa) 
after stent placement is limited by the ferromagnetic artifacts caused by most stents.(18) DUS as a 
follow-up modality offers several advantages: being widely available, non-invasive, relatively 
inexpensive, and well tolerated by patients as it does not require iodinated contrast media. DUS 
in the evaluation of initial patency and subsequent surveillance after renal artery 
revascularization has been recommended.(19, 20, 21)  
 
Renal artery angioplasty and stent placement are generally well-tolerated procedures. As 
compared to stand-alone balloon angioplasty, renal artery stenting is associated with improved 
immediate results and a decrease in the rate of restenosis.(22) Complications include contrast-
induced nephropathy, thrombosis, distal embolization, renal artery dissection, and perforation.(17) 
Distal protection devices are attractive for safeguarding against the effects of distal embolization 
and are currently under investigation.(6) However, the short length of renal arteries and lack of a 
safe landing zone for placement of distal protection devices is a limiting factor. An alternative 

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strategy could be the use of covered stents. 
 
The use of polytetraflouroethylene (PTFE) covered stents is designed to combine the 
effectiveness of surgical treatment with the minimal invasiveness of endovascular treatment.(23) 
The stent-associated PTFE derived graft layer creates a mechanical barrier between the arterial 
lumen and wall, theoretically improving patency.(24) This method prevents exposure of the vessel 
wall to constituents of blood that may initiate the intimal hyperplastic process which may reduce 
the incidence of in-stent restenosis.(24) Lakshminarayan et al suggests that because covered stents 
could potentially exclude thrombus from within the lumen of lesions with large thrombus 
burden, there may be a role for these stents in reducing distal embolization. 
 
1.1 
INVESTIGATIONAL DEVICE  
The iCAST™ RX Stent System consists of a balloon-expandable covered stent and a balloon 
dilation catheter. The stent is constructed out of 316L surgical stainless steel. The one piece stent 
cover is constructed out of a tubular form of expanded polytetraflouroethylene (ePTFE).  The 
covering is attached in a manner such that both the inner lumen and outer surface of the stent are 
encapsulated with the ePTFE cover material. The stent is radio-opaque under fluoroscopy. The 
covered stent is mounted and crimped onto the dual lumen rapid exchange balloon catheter 
(delivery system) so that the system is ready for use by the clinician.  
 
The balloon catheter shaft is comprised of two main sections: a distal coaxial section comprised 
of a thermoplastic inner tube and thermoplastic outer tube and a proximal section comprised of a 
304 stainless steel hypo tube assembly. The proximal end of the coaxial section is attached to the 
distal end of the hypo tube. A non-compliant thermoplastic dilatation balloon is attached onto the 
distal aspect of the coaxial catheter section. Radiopaque markers are affixed to the inner tube of 
the distal catheter section to identify the dilatation zone of the balloon. The distal catheter tip is 
tapered to facilitate advancement of the catheter to and through the stenosis. The proximal hypo 
tube assembly section of the catheter is comprised of a stainless steel hypo tube with an 
overmolded locking female Luer hub attached to one end to allow attachment of a male locking 
Luer fitting (syringe/inflation device). The attached female Luer hub is molded out of clear 
plastic to assist the user with purging the device of air during preparation. A strain relief is 
affixed over the Luer hub and is printed with the device information (stent length, deployed stent 
diameter, guide wire size, and company logo).  
 
The catheter main lumen (annular space between the inner and outer coaxial tubes and lumen of 
hypo tube assembly) is used for inflation and deflation of the attached balloon. The secondary 
lumen (lumen of the inner tube of coaxial assembly), is referred to as the Rapid Exchange (RX) 
lumen and is used for guide wire introduction. The inner and outer tubes are joined 
approximately 25cm from the distal tip to form the guide wire access port. The catheter will be 
available in two working lengths: 80cm and 140cm. Balloons will be available in diameters of 5, 
6, and 7mm and in lengths to accommodate the length of each stent. Table 1: iCAST™ RX Stent 

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Sizes: 
Table 1: iCAST™ RX Stent Sizes 
Length 
Diameter (expanded) 
5mm 
6mm 
7mm 
16mm 
√ 
√ 
√ 
21mm 
√ 
√ 
√ 
24mm 
√ 
√ 
√ 
1.2 
INDICATION FOR USE  
The iCAST™ RX Stent System (iCAST RX) is indicated for the improvement in blood pressure 
control for use as an adjunct to balloon angioplasty of de novo or restenotic lesions (≤ 16mm in 
length) of the renal artery, with a reference vessel diameter of 5.0mm to 7.0mm to assist in the 
maintenance of vessel patency.  
 
 
Refer to the manufacturer’s Instructions for Use (IFU) for instructions including: sizing and 
selection of the stent, preparation of the stent and delivery catheter, introduction and positioning 
of the stent, deployment of the stent, removal of an unexpanded stent, and emergency withdrawal 
of an expanded stent. 
 
2.0 
TRIAL OBJECTIVES  
2.1 
RATIONALE 
The primary goal of revascularization therapy is the re-establishment and maintenance of 
adequate blood flow within the renal artery to perfuse the kidney.  ARTISAN will investigate the 
re-establishment of adequate blood flow and normalized pressure in the renal artery and its effect 
on blood pressure in patients with resistant hypertension. In this single-arm trial, primary 
endpoints have been determined to show the safety, effectiveness, and clinical outcomes of the 
iCAST™ RX Stent System. Safety and effectiveness will be evaluated based on the primary 
patency rate at 9-months on a per lesion basis evaluated against a performance goal of published 
studies with bare-metal stents. The primary clinical endpoint will assess the improvement in SBP 
at 9-months as compared to baseline SBP.  
 
The primary functional endpoint of primary patency has been established since the clinical care 
of the physician is considered a more objective measurement of stent performance than the 
restenosis measurement of DUS alone.  In standard practice, a DUS is used to determine patency 
of a stent.  If a DUS is negative and the patient is asymptomatic, no intervention is typically 
conducted by a physician.  If a patient is symptomatic or a DUS is positive, a confirmatory 
angiogram is typically performed to assess the patency of the vessel.  
 
To properly match the functional outcomes with historical data, the endpoint will be calculated 
on a per lesion basis. This reflects the current standard of care of treating patients with single 

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vessel renal artery lesions and those patients with bilateral renal artery stenosis. Analysis of past 
studies has demonstrated that the number of lesions treated per patient has increased with 
time.(26) A recent renal trial reported 1.2 lesions per patient were treated.(27) To calculate on a per 
patient level for this endpoint would bias the results and overestimate the failure rate compared 
to a per lesion analysis, as more lesions would be at risk for restenosis but would not be 
accounted for in a per patient analysis. 
 
DUS is an established safe, noninvasive, reproducible, and sensitive method of detecting and 
following renal artery lesions that provides both morphological and functional assessments of the 
renal arteries.(22, 28, 29, 30, 31, 32) There are limits with relying exclusively on DUS for evaluating 
residual stenosis post-renal stenting. Velocity information such as peak systolic velocity (PSV) 
and renal aortic ratio (RAR) correlate with angiographic stenosis but these DUS criteria, 
developed for native renal arteries within renal artery stents has not been studied extensively.(25) 
The extremes of ARAS can lead to a variety of waveform and flow velocity abnormalities and 
the entire main renal artery must be visualized in order to perform an adequate examination.(24) 
There are documented technical disadvantages to DUS as it is very operator dependent and as 
such, is associated with higher technical failure rate than other diagnostic modalities, in part due 
to the steep learning curve associated with the technique. To mitigate the challenges with DUS 
interpretation, clinical validation through independent noninvasive core laboratory and/or 
angiography will be required in order to correctly validate and definitively assess residual 
percent diameter stenosis. DUS is highly reliable in identifying widely patent stents. However, 
correlation studies of DUS with angiography have confirmed that DUS is not as accurate when 
results suggest a stenosis. To mitigate the risk of inaccurate readings, if a stenosis is detected, an 
alternate means of clinical validation will be used to definitively assess patency. 
 
The primary clinical endpoint of reduction in SBP has been established to determine the benefit 
of revascularization therapy to perfuse the kidney.  The Framingham Heart Study showed that 
decreasing SBP by 10mmHg can be lifesaving. Additionally, Joint National Committee VII (JNC 
VII) estimates that a 5mmHg reduction in SBP would reduce the incidence of stroke in patients 
by 14%, coronary heart disease (CHD) by 9%, and overall mortality by 7%.(33) JNC VII also 
presented data from a UK diabetes study that demonstrated a 10mmHg decrease in SBP was 
associated with average reductions of 15% for diabetes-related mortality, 11% for MI, and 13% 
for microvascular complications of retinopathy or nephropathy.(33) Currently accepted indications 
for revascularization are significant ARAS with progressive or acute deterioration of renal 
function and/or severe uncontrolled hypertension; the key point for success is the correct 
selection of the patient.(34) When performed correctly, renal artery stenting had been shown to 
stabilize or improve renal function and/or renovascular hypertension in 65-70% of carefully 
selected patients with ARAS.(1) It is under this guidance that patients with uncontrolled 
hypertension will be selected by specific angiographic and clinical selection criteria for this trial.  
 
While previous clinical studies have not consistently shown a direct beneficial effect on 

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hypertension or renal function, revascularization therapy potentially eliminates one of the several 
factors that contribute to hypertension. This may be supported by the fact that some patients do 
show a stabilization or improvement in their hypertension following revascularization. Clinical 
data show that successful renal artery stenting permits reintroduction of ACE inhibitors in some 
patients which in turn leads to satisfactory maintenance of renal function.(35) Current clinical 
experience does not allow one to predict exactly which patients may experience a clinical benefit 
from renal artery stenting. It is hypothesized that revascularization therapy for hemodynamically 
significant lesions may facilitate the stabilization or reduction of blood pressure in conjunction 
with ongoing medical therapy for some portion of patients whose blood pressure is otherwise 
refractory to medical treatment. 
 
The inclusion/exclusion criteria in the ARTISAN trial seeks to target subjects likely to respond 
positively based on findings observed in the VIVA performance goals for blood pressure 
treatment.  In the VIVA paper, patients are selected specifically for blood pressure improvement 
based on the review of three prior studies that suggest patients with resistant hypertension with a 
systolic blood pressure > 155mmHg, have been medically optimized with 3 or more hypertensive 
medications, and a lesion that is hemodynamically significant (or gradient) will have a likelihood 
of having a blood pressure improvement beyond medical therapy alone.(36) 
 
The ARTISAN trial will assess the impact of additional clinical outcomes in this patient 
population such as improvements in systolic blood pressure and renal function as determined by 
eGFR. Additionally, MAEs, the number and dose of antihypertensive medications used, 
technical success, acute procedural success, 30-day clinical success, and TLR will be assessed as 
part of the secondary endpoint analysis. The American Heart Association scientific statement, 
Guidelines for the Management of Patients with Peripheral Arterial Disease 2006, in 
combination with discussions with expert physicians and data provided from review of previous 
clinical trials of renal artery stents, were used to select the primary and secondary endpoints as 
applicable measures of device effectiveness and safety.(37) 
 
Renal artery stent placement has gained increasing acceptance on the basis of historical results of 
renal angioplasty and the attractiveness of percutaneous compared with surgical 
revascularization.(38) As a result, primary stenting of lesions has become the standard of care.  In 
this study, primary stenting of the target lesion will be performed where possible. The enrollment 
criterion of the ARTISAN trial has selected patients with hemodynamically significant stenoses 
and where necessary, pre-dilatation will be performed due to narrowing of the lumen diameter of 
the stenosis compared to the size of the device being inserted.  This strategy is selected to 
minimize the risk of distal embolization and stent dislodgment during deployment. 
 
In conclusion, the safety, effectiveness, and clinical benefit of reducing blood pressure with the 
iCAST™ RX Stent System will be evaluated under the ARTISAN trial design. 

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2.2 
CO-PRIMARY ENDPOINTS 
Functional Endpoint 
Assessment of primary patency rate at 9-months, defined as continuous patency without the 
occurrence of a total occlusion of the original lesion, without a re-intervention to treat a partial or 
total occlusion of the stented segment, or bypass of the stented segment due to clinically-driven 
restenosis or occlusion.  
 
Clinical Endpoint 
Improvement in systolic blood pressure (SBP) at 9-months as compared to baseline systolic 
blood pressure. 
2.3 
SECONDARY ENDPOINTS 
The secondary endpoints will provide: 
  
1. The occurrence of procedure-related MAEs reported as percentage of subjects 
with MAE, at 30-days, 9-months, 12-months, 24-months, and 36-months. 
Inclusive of: 
a. Procedure-or device-related occurrence of death 
b. Q-Wave MI 
c. Clinically driven TLR 
d. Significant embolic events  
i. Defined as unanticipated kidney/bowel infarct clinically driven 
by symptoms of abdominal or back pain and confirmed with 
CT scan or open surgery, lower extremity ulceration or 
gangrene, or kidney failure after 30-days, 9-months, 12-
months, 24-months, and 36-months. 
2. Technical success defined as successful delivery and deployment of the 
iCAST™ RX Stent System with ≤ 30% residual angiographic stenosis after 
covered stent deployment (including post-dilatation) assessed via QVA by an 
independent core laboratory. 
 
3. Procedural success defined as technical success without the occurrence of MAE 
prior to hospital discharge. 
 
4. TLR measured as the proportion of subjects that require a clinically-driven 
reintervention of the target lesion through 9-months.   
a. A clinically-driven TLR is defined as a TLR (PTA, bare metal stent or 
repeat covered stent deployment, or surgical bypass) due to 
documented recurrent hypertension from 30-days post-procedure level 
and/or deterioration in renal function from baseline value, associated 
with angiographic core laboratory adjudication of a ≥ 60% diameter 
covered stent restenosis.  
 
5. Rate of incidental TLR defined as rate of TLRs not meeting the definition of a 

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clinically driven TLR.  
 
6. Improved SBP control assessed at 30-days, 9-months, 12-months, 24-months 
and 36-months. 
 
7. Secondary patency rate at 9-months after a clinically-driven TLR which restores 
patency after total occlusion. 
8. Change in number and dosage of anti-hypertensive medications as compared to 
baseline. 
9. Renal function compared to baseline as measured by eGFR at 30-days and 9-
months. 
 
 
3.0 
TRIAL DESIGN AND POPULATION  
 
This is a prospective, single-arm, multicenter clinical trial that will take place at up to 25 
US/OUS sites. Primary endpoints have been determined to show the safety, effectiveness, and 
clinical outcomes of the iCAST™ RX Stent System. Safety and effectiveness will be evaluated 
based on the primary patency rate at 9-months on a per lesion basis evaluated against a 
performance goal of published studies with bare-metal stents. The primary clinical endpoint will 
assess the improvement in systolic blood pressure at 9-months as compared to baseline systolic 
blood pressure.  
 
Eligible subjects will undergo a two-week Medical Documentation Screening period to confirm 
resistant hypertension (SBP ≥ 155mmHg) while on maximum tolerable dose of ≥  three anti-
hypertensive medications from at least three classes of drugs, one of which must be a diuretic.  
 
There must be documented clinical evidence to support likelihood of angiographic findings > 
80% whether it is DUS, CTa, MRa or other medical evidence. After meeting screening and 
clinical eligibility criteria, subjects will undergo a baseline assessment for angiographic 
eligibility. After angiographic documentation of a ≥ 80% diameter renal artery stenosis or FFR < 
0.8 is confirmed the subject may be enrolled in the trial by placement of the investigational 
device.  
 
The 9-month visit will include a follow-up DUS of the target renal artery. If the DUS is non-
diagnostic due to an imaging problem, such as overlying bowel gas or body habitus, a second 
DUS may be attempted. If the DUS is indicative of ≥ 60% stenosis as determined by the core 
laboratory, or the second DUS remains non-diagnostic, a contrast angiogram will be used to 
assess the degree of restenosis of the covered stent(s).  
 
Clinical follow-up visits will be required for all enrolled subjects at 30-days, 9-months, 12-
months, 24-months and 36-months.  A 6-month and 18-month visit will occur via telephone to 

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collect medication usage and AEs only.  The 36-month clinic office visit will be required as the 
final safety visit.  
3.1 
DETERMINATION OF TRIAL ELIGIBILITY  
Subjects eligible for initial trial screening will present with renal artery stenosis and meet ALL of 
the inclusion criteria in order to be considered for the ARTISAN trial.  If ANY of the exclusion 
criteria are met, the subject cannot be enrolled in the trial or treated using the investigational 
device.   
 
The Medical Monitor will provide oversight in the enrollment of subjects during the course of 
the trial. All potential subjects will be reviewed and approved by the Medical Monitor, prior to 
enrollment, to ensure the subjects have met all general Inclusion/Exclusion criteria. Once the 
subject has been reviewed and approved by the Medical Monitor, the subject may proceed to the 
index procedure. 
 
A subject is deemed enrolled into the trial once all inclusion criteria have been met and reviewed 
by an independent medical monitor, no exclusion criteria exist, the operator determines the target 
lesion is ≥ 80% diameter stenosis or FFR < 0.8 and the trial device enters the subject. All adult 
subjects will be counseled on and instructed to read and sign the required ICF prior to conducting 
any trial related procedures. 
3.2 
INCLUSION CRITERIA  
Subjects must meet ALL of the inclusion criteria to be considered for the trial: 
General Inclusion Criteria: 
1. Age ≥ 18 at the time of informed consent. 
2. Subject or subject’s legal representative have been informed of the nature of the trial, 
agrees to participate and can comply with study procedures and follow-up, and has signed 
an IRB/EC approved ICF. 
3. Subjects that have bilateral kidneys or a solitary functioning kidney with Renal Artery 
Stenosis in at least one kidney and an average SBP ≥ 155mmHg. 
4. Subject has a history of maximum tolerable dose of ≥ 3 anti-hypertensive medications of 
different classes, one of which must be a diuretic (for at least two weeks prior to Medical 
Documentation Screening period).  
a. A documented history for a minimum of 3 months showing reasonable and 
aggressive efforts to manage hypertension prior to consent. This must include the 
use of a broad variety of medications that have been used and failed or not 
tolerated.  
5. Subject must have documented clinical evidence to support likelihood of angiographic 
findings > 80% whether it is DUS, CTa, MRa or other medical evidence.. 
6. NYHA class I, II, or III the time of trial enrollment. 

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NOTE: When a subject has bilateral Renal Artery Stenosis both of which require stenting, it 
is recommended to treat both kidneys with an iCAST™ RX Stent System during the index 
procedure. In the event that a subject needs a renal stenting procedure staged for renal 
protection, it is important that the Investigator treats the second renal artery with an iCAST™ 
RX Stent System after 30 days of the index procedure. If subjects with bilateral stenosis have 
only one lesion that meets protocol inclusion criteria that lesion should be treated per 
protocol. The recommendation is to NOT treat the second non-qualifying lesion, however if 
the operator feels strongly it is indicated, then they should treat per standard of care after 30-
days post index procedure in order to comply with exclusion criteria #10. 
Subjects with flash pulmonary edema are allowed into the trial should they meet all other 
Inclusion and Exclusion criteria. 
Angiographic Anatomic Inclusion Criteria: 
1. Angiographic diameter renal artery stenosis ≥ 80% involving unilateral or bilateral renal 
arteries.  
a. The degree of percent diameter stenosis for all lesions intended to be treated, must 
be confirmed via one of the following methods: 
i. Manual or automated measurement with calipers 
ii. Measured FFR < 0.8 using a pressure wire 
iii. Measured translesional peak pressure gradient of > 21mmHg after induced 
hyperemia via dopamine or papaverine using a 4Fr or less catheter or 
pressure wire. 
b.  Subjects with 60-79% angiographic stenosis who have confirmed FFR < 0.8 may 
be enrolled. 
2. Renal pole-to-pole length > 8cm (per visual estimate). 
3. Target lesion length ≤ 16mm per vessel (per visual estimate). 
4. Renal artery vessel diameter ≥ 5.0mm and ≤ 7.0mm (per visual estimate).  
5. Lesion originating ≤ 15mm of the renal ostium. 
3.3 
EXCLUSION CRITERIA  
Subjects will be excluded if ANY of the following conditions apply:  
 
General Exclusion Criteria: 
1. Subject’s estimated life expectancy is < 12 months. 
2. Subject has a history of transplanted kidney(s), has had another recent organ transplant or 
polycystic kidney disease. 
3. Subject with estimated eGFR ≤ 25mL/min/1.73m2 
4. Subject has a history of bleeding diathesis or coagulopathy or refuses blood transfusions. 
5. Subject has a known contraindication to heparin, aspirin, thienopyridine, other anti-
coagulant/antithrombotic therapies, contrast media, stainless steel, and/or PTFE. 
6. Subject has had a previous renal bypass operation, a bypass is planned, or the target 
lesion is located within or beyond a bypass graft. 

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7. Subject has received a thrombolytic agent within the past 30 days.  
8. Subject has documented acute pulmonary edema or systolic heart failure with ejection 
fraction < 30% and/or hospitalization requiring intubation and ventilation support for this 
diagnosis within the previous 90 days or hypertensive emergencies defined as resulting in 
organ damage. 
9. Concurrent enrollment in any investigational trial wherein subject’s participation has not 
been completed.  
10. Subject has had a planned or anticipated cardiovascular surgical or interventional 
procedure outside of the affected renal artery (including, but not limited to, aortic, renal, 
cardiac, carotid, femoro-popliteal, and below the knee) within 30 days prior to the index 
procedure and prior to completion of the 30 day follow–up. 
11. Subject has suffered a stroke or Transient Ischemic Attack (TIA) in the past 3 months.  
12. Subject is pregnant, lactating, or is of child-bearing potential and plans to become 
pregnant during the follow-up trial period. 
13. Subject with significant valvular disease. 
14. Subject with known significant proteinuria > 2+ or > 2.0gm/d. 
15. Subject with known bilateral upper-extremity arterial stenosis that result in spuriously 
low arm pressures or without the ability to gain reliable blood pressure measurements in 
at least one upper extremity. 
16. Subject with active sepsis. 
17. Subject with serum creatinine ≥ 3.0mg/dL. 
18. Subject with NYHA Class IV at the time of enrollment. 
19. Subject is on hemodialysis. 
20. Subject has a history of renal aneurysm. 
21. Subject with cardiogenic shock. 
22. Subject with cardiomyopathy. 
23. Subject has an uncontrolled concurrent illness, including but not limited to ongoing or 
active infection or active autoimmune disease requiring immunosuppressive therapy. 
24. Any subject with clinically significant cardiovascular, respiratory, neurologic, hepatic,  
endocrine, major systematic disease, making implementation or interpretation of the 
protocol or protocol results difficult or who in the opinion of the investigator would not 
be a good candidate for enrollment. 
Anatomic Exclusion Criteria: 
1. The planned site of intervention is totally occluded or has an anatomic configuration 
likely to prohibit adequate dilatation, and/or passage or implantation of the 
investigational device. 
2. Subject has multiple ipsilateral lesions of the target renal artery that cannot be covered by 
a single stent. 
3. There is a previously implanted stent in the target vessel or there is a previously 
implanted stent in the contralateral vessel < one year. 

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4. Subject has fibromuscular dysplasia, in renal artery and/or other vascular bed. 
 
5. The target lesion site is associated with a thrombus. 
6. Target lesion treated with laser atherectomy, directional atherectomy or other adjuncts to 
PTA. 
7. Subject has a critical stenotic (> 70%) small accessory renal artery. 
8. Subject has an abdominal aortic aneurysm > 4.0cm in diameter or a severe atherosclerotic 
aorta. 
9. Main renal artery length ≤ 15mm precluding the safe deployment of a covered renal stent.  
10. Any lesion that would include blocking of renal artery side branch.  
11. Renal artery stenosis due to dissection of renal artery: spontaneous or traumatic. 
 
3.4 
SUBJECT SCREENING  
At each investigational site, a member of the trial research team will approach individual 
subjects (or their legal representative or guardian) who are potential candidates for participation. 
A trial research staff member will explain the purpose, procedures, device, and intent of the trial 
to each potential participant. Interested subjects will be invited to join the trial and asked to 
provide written informed consent prior to initiation of any trial related procedure.  
 
A focused hypertension medical history will be reviewed and recorded for each subject. History 
should capture at least three months’ information prior to screening to document that reasonable 
and aggressive efforts were previously made to manage hypertension via a broad variety of 
medications that have been tried and failed. Potential subjects will have been on a stable 
medication regimen for a minimum of two weeks prior to beginning the Medical Documentation 
Screening period. A minimum of a 14-day Medical Documentation Screening period is required 
to refine case selection and identify subjects most likely to benefit from renal revascularization*. 
Titration of the subject’s antihypertensive medications will not be allowed during this period. 
The Medical Documentation Screening period will proceed in the following sequence: 
 
1. Potential subjects will complete an initial office visit during which 3 blood pressure 
measurements will be obtained, utilizing a standardized technique (APPENDIX 3: 
METHODOLOGY FOR OFFICE-BASED BP MEASUREMENT), to determine an 
average SBP value.  If the average initial SBP value for this visit is ≥ 150mmHg, then the 
subject will proceed to step 2. 
 
2. The subject will be tested for proteinuria, have labs drawn, can be scheduled for the 
procedure, and will proceed to step 3. 
 
 
 
 Throughout the Medical Documentation Screening period, subjects will complete 

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a daily questionnaire every day until the day of procedure that will ask if the 
subject is taking blood pressure medications as prescribed. 
 If the subject has recorded daily medication compliance via the completed 
questionnaire, the subject proceeds to step 3. 
3. Subjects will have their BP taken in the office every two weeks prior to the scheduled 
procedure. Only subjects with an average SBP value ≥ 150mmHg at this visit after 3 
sequential blood pressure measurements are taken, utilizing a standardized technique  
(APPENDIX 3: METHODOLOGY FOR OFFICE-BASED BP MEASUREMENT), will 
be allowed to proceed.  
 A minimum of two office visits are required within the 14 day Medical 
Documentation Screening period. If the procedure is scheduled for more than 14 
days from the first visit, subjects should return every two weeks (+/- 3days) for 
BP assessment and monitoring and the daily questionnaire for medication 
compliance should be continued until the day of procedure. 
 
4. On the day of the scheduled procedure, or no more than 14 days prior, 3 sequential blood 
pressure measurements will be taken again, utilizing a standardized technique 
(APPENDIX 3: METHODOLOGY FOR OFFICE-BASED BP MEASUREMENT), to 
determine an average SBP value.  Only subjects with an average SBP of ≥ 155mmHg 
from the three measurements taken on the last day of the 14-day Medical Documentation 
Screening period will be considered for enrollment. 
 
*NOTE: If a subject is seen in the clinic with a medical history documenting at least a 1 month 
stable medication of ≥ three anti-hypertensive medications from at least three classes of drugs, 
one of which being a diuretic and documented SBP ≥ 155mmHg, they will be allowed to skip the 
formal Medical Documentation Screening period and to be enrolled as soon as the history and 
baseline labs are reviewed by the Medical Monitor. Subjects must complete the daily 
questionnaire from the day of consent through the day of procedure. All other protocol 
requirements that would have normally occurred during the two week screening period must still 
be completed even if the screening period is skipped. These assessments include: vitals, BP, 
Labs, test for proteinuria, physical exam, and a pregnancy test and would need to be completed 
either on the day of consent or prior to the day of procedure. 
 
 

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Figure 1: Medical Documentation Screening Period Flow Diagram            
 
 
 
 
Identification of potential subjects: 
On medical regimen of ≥ 3 anti-hypertensive medications 
AND 
Reported SBP ≥ 150mmHg 
 
 
 
SCREENING STEP 1 
 
Initial office based 
Blood Pressure screening 
Labs drawn 
If mean SBP ≥ 150mmHg
If mean SBP      
< 150mmHg 
Screen failure 
  
 
SCREENING STEP 3 
 
Tested for proteinuria, can 
be scheduled for 
procedure, and complete 
daily questionnaire 
 
If mean SBP 
 < 150mmHg  
OR  
self-reported medical 
non-compliance 
Screen failure 
If mean SBP ≥ 150mmHg  
AND 
self-reported medical compliance 
SCREENING STEP 4 
 
Day of procedure 
Blood Pressure Screening 
If mean SBP 
< 155mHg 
Screen failure 
If mean SBP ≥ 155mmHg 
Eligible for enrollment
Medical 
Documentation  
Screening 
 period 

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3.5 
SUBJECT ENROLLMENT  
Up to 138 subjects will be enrolled in this clinical trial. Eligible subjects will be enrolled 
consecutively at each investigational site. A patient is deemed enrolled into the trial once all 
inclusion criteria have been met and reviewed by an independent medical monitor, no exclusion 
criteria exist, the operator determines the target lesion is ≥ 80% diameter stenosis or FFR < 0.8 
and the trial device enters the subject.  The screening log will then be completed to document the 
enrollment, subject number, or reason for non-enrollment of subjects screened but not enrolled in 
the ARTISAN trial. 
3.6 
SUBJECT DISCONTINUATION 
Each enrolled subject shall remain in the trial until completion of the required follow-up period, 
however, a subject’s participation in any clinical trial is voluntary and the subject has the right to 
withdraw at any time without penalty or loss of standard of care treatment. Conceivable reasons 
for discontinuation may include, but not be limited to, the following: 
1. Subject death 
2. Subject voluntary withdrawal  
3. Subject withdrawal by physician as clinically indicated 
 
The reason for subject discontinuation must be documented on the electronic Case Report Form 
(eCRF) and source documents. Investigators must also report all subject discontinuations to their 
IRB/EC as defined by their Institution’s procedure.  
3.7 
SUBJECT WITHDRAWAL  
All subjects should be encouraged to remain in the trial throughout the entire follow up time 
period.  If a subject decides to discontinue trial participation, the reason for their discontinuation 
must be recorded in the medical record and submitted via the eCRF. Subjects who discontinue 
participation prematurely will be included in the analysis results if the 9-month visit has been 
reached.  
3.8 
EARLY TERMINATION OF THE TRIAL 
Possible reasons for early trial termination include: 
1. Unanticipated Adverse Device Effects (UADEs) present an unreasonable risk to subjects. 
2. The Data Safety Monitoring Board (DSMB) makes a decision for the early termination of 
the trial per recommendation (refer to Section 7.1). 
 
If the trial is terminated early, Atrium will provide a written statement to the Investigator to 
enable notification to their IRB/EC. 
 
 
 
 

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4.0 
PROCEDURES AND ASSESSMENTS  
 
A table summarizing the study procedures is presented in APPENDIX 4: SCHEDULE OF 
EVENTS. A summary of the assessments to be performed at each interval is presented below. 
 
The following diagram summarizes the timing of visits in this trial: 
 
Figure 2: Trial Flow Diagram 
 
 
Evaluation of 
angiographic eligibility 
criteria 
Angiographic 
exclusion criteria 
Screen failure
All angiographic eligibility met
Subject enrolled at time of stent placement 
 
N =138 
 
 
Informed consent process completed 
14-Day Medical Documentation Screening period completed 
All clinical inclusion criteria met 
30-day (-7/+14 days) follow-up 
6-month (+/- 30 days) follow-up (phone visit) 
9-month (+/- 30 days) follow-up  
Primary Endpoint Assessments 
12-month (+/- 30 days) follow-up  
18-month (+/- 30 days) follow-up (phone visit) 
24-month (+/- 60 days) follow-up  
36-month (+/- 60 days) follow-up 
Final Trial Endpoint Assessments 

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4.1 
SCREENING PROCEDURES  
At each investigational site, a member of the trial research team will approach individual 
subjects (or their legal representative) who are potential candidates for participation. A trial 
research staff member will explain the purpose, procedures, device, and intent of the trial to each 
potential participant. Interested subjects will be invited to join the trial and asked to provide 
written informed consent prior to initiation of any trial related procedure.  
4.1.1 DAY -14: INITIAL MEDICAL DOCUMENTATION SCREENING VISIT 
Trial subjects will complete an initial office visit.  The assessment will consist of: 
 Signed ICF 
 Inclusion/exclusion criteria 
 Demographics 
 Collection of medical history 
 Collection of focused anti-hypertensive medical history 
 Height/weight 
 Vital signs 
 Collection of BP (following the methodology for measurement as outlined in 
APPENDIX 
3: 
METHODOLOGY 
FOR 
OFFICE-BASED 
BP 
MEASUREMENT)  
 Laboratory assessments 
o Chem12 Panel which includes: Glucose, Calcium, Albumin, Total protein, 
Sodium, Potassium, CO2, Chloride, BUN, creatinine, ALP, ALT, AST, 
and bilirubin. 
o Test for proteinuria. Urine proteinuria may be tested by dipstick. A level 
of > 2+ is exclusionary unless a 24 hour urine shows that the urinary 
protein is < 2gm/d. 
 Physical exam 
 Female subjects of childbearing potential will have a pregnancy test  
 Documented clinical evidence to support likelihood of angiographic findings > 
80% whether it is DUS, CTa, MRa or other medical evidence  
 Collection of concomitant medications 
 
4.1.2 DAY -7: MEDICAL DOCUMENATION SCREENING VISIT(S) 
Trial subjects will return to the office every 2 weeks prior to the scheduled procedure to 
monitor their BP. Assessments will consist of: 
 Collection of BP (following the methodology for measurement as outlined in 
APPENDIX 
3: 
METHODOLOGY 
FOR 
OFFICE-BASED 
BP 
MEASUREMENT) 
 Collection of concomitant medications 
 Collection of AEs, if applicable  
 
 

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4.2 
PRIOR TO THE PROCEDURE  
The following tests and examinations must be performed prior to the procedure to verify 
eligibility. 
4.2.1 DAY 0: DAY OF PROCEDURE 
 
Trial subjects will return to the office the day of the scheduled procedure. Assessments 
will consist of: 
 Inclusion/exclusion criteria 
 Vital signs 
 Collection of BP (following the methodology for measurement as outlined in 
APPENDIX 
3: 
METHODOLOGY 
FOR 
OFFICE-BASED 
BP 
MEASUREMENT) 
 Laboratory assessments 
o Chem12 Panel  
 Physical exam 
 Female subjects of childbearing potential will have a  pregnancy test  
 Collection of concomitant medications 
 Collection of AEs, if applicable  
 Begin dual anti-platelet therapy (aspirin plus thienopyridine) pre-procedure as 
required per Table 2: Concomitant Medications 
 
4.2.2 DAY 0: ANGIOGRAPHY 
Angiography is to be performed according to standard hospital procedure for renal 
stent implantation and in compliance with procedures outlined in the Angiographic 
Core Laboratory Manual of Operations.  
4.3 
STENT IMPLANTATION 
Implantation of the iCAST™ RX Stent System should be performed according to the IFU 
provided with the investigational device. Refer to the manufacturer’s IFU for instructions 
including: sizing and selection of the stent, preparation of the stent and delivery catheter, 
introduction and positioning of the stent, deployment of the stent, removal of an unexpanded 
stent, and emergency withdrawal of an expanded stent. 
 Administer IV heparin, low molecular weight heparin, or bivalirudin per routine 
hospital practice. Target Activated Clotting Time (ACT) must be >250 seconds prior 
to implantation of the iCAST™ RX Stent System if heparin or low molecular weight 
heparin is administered. Bivalirudin should be administered in line with the 
prescribing information according to the weight of the patient.  
 NOTE: Pre-dilatation of the lesion and the use of distal protection filters will be at the 
Investigators discretion and are not distinctly prohibited nor required. 
 
4.4 
IMMEDIATE POST-PROCEDURE  
Post-procedure, subjects should continue dual anti-platelet therapy (aspirin plus thienopyridine) 
for a minimum of 3 months except when it is medically necessary to take subjects off therapy. 

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 Collection of AEs, if applicable  
4.5 
POST PROCEDURE FOLLOW-UP EVALUATIONS 
All trial subjects will be followed through hospital discharge and will undergo follow-up 
evaluations for a total of 36 months at the following time points: 
 
4.5.1 DAY 30 (+14/-7 DAYS): FOLLOW-UP VISIT 
Trial subject follow-up clinic evaluation must occur 30 days post-procedure.  The 
assessment will consist of: 
 Vital signs 
 Collection of BP (following the methodology for measurement as outlined in 
APPENDIX 
3: 
METHODOLOGY 
FOR 
OFFICE-BASED 
BP 
MEASUREMENT) 
 Laboratory assessments 
o Chem12 Panel  
 Physical exam 
 DUS 
 Collection of concomitant medications 
 Collection of AEs, if applicable 
 Subjects remain on dual anti-platelet therapy as required per Table 2: 
Concomitant Medications 
 
4.5.2 6-MONTH (+/-30 DAYS) PHONE CALL  
Trial subject follow-up telephone evaluation must occur 6 months post-procedure.  The 
assessment will consist of: 
 Collection of concomitant medications 
 Collection of AEs, if applicable 
 
4.5.3 9-MONTH (+/- 30 DAYS) FOLLOW-UP VISIT  
Trial subject follow-up clinic evaluation must occur 9 months post-procedure.  The 
assessment will consist of: 
 Vital signs 
 Collection of BP (following the methodology for measurement as outlined in 
APPENDIX 
3: 
METHODOLOGY 
FOR 
OFFICE-BASED 
BP 
MEASUREMENT) 
 Laboratory assessments 
o Chem12 Panel  
 Physical exam 
 DUS* 
 *Angiography if DUS indicates ≥ 60% stenosis 
 Collection of concomitant medications 
 Collection of AEs, if applicable 

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4.5.4 12-MONTH (+/- 30 DAYS) FOLLOW-UP VISIT  
Trial subject follow-up clinic evaluation must occur 12 months post-procedure.  The 
assessment will consist of: 
 Vital signs 
 Collection of BP (following the methodology for measurement as outlined in 
APPENDIX 
3: 
METHODOLOGY 
FOR 
OFFICE-BASED 
BP 
MEASUREMENT) 
 Physical exam 
 Collection of concomitant medications 
 Collection of AEs, if applicable 
 
4.5.5 18-MONTH (+/- 30 DAYS) PHONE CALL  
Trial subject follow-up telephone contact evaluation must occur 18 months post-
procedure.  The assessment will consist of: 
 Collection of concomitant medications 
 Collection of AEs, if applicable 
 
4.5.6 24-MONTH (+/- 60 DAYS) FOLLOW-UP VISIT 
Trial subject follow-up clinic evaluation must occur 24 months post-procedure.  The 
assessment will consist of: 
 Vital signs 
 Collection of BP (following the methodology for measurement as outlined in 
APPENDIX 
3: 
METHODOLOGY 
FOR 
OFFICE-BASED 
BP 
MEASUREMENT) 
 Physical exam 
 Collection of concomitant medications 
 Collection of AEs, if applicable 
 
4.5.7 36-MONTH (+/- 60 DAYS) FOLLOW-UP VISIT 
Trial subject follow-up clinic evaluation must occur 36 months post-procedure.  The 
assessment will consist of: 
 Vital signs 
 Collection of BP (following the methodology for measurement as outlined in 
APPENDIX 
3: 
METHODOLOGY 
FOR 
OFFICE-BASED 
BP 
MEASUREMENT) 
 Physical exam 
 Collection of concomitant medications 
 Collection of AEs, if applicable 
 
 

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4.6 
CONCOMITANT MEDICATIONS 
All medications (prescription, herbal, and over-the-counter) taken from the time of informed 
consent through 3 years must be recorded in the subject’s source records and transcribed into the 
concomitant medication section of the eCRF. 
 
Subjects are required to receive dual anti-platelet therapy pre-procedure and for a minimum of 3 
months post-procedure. The required medications for this study are listed below. 
 
Table 2: Concomitant Medications 
Timing  
Medication  
Procedure  
Prior to Procedure  IV Heparin or low molecular 
weight heparin or bivalirudin 
Per routine hospital practice  
 
Acetylsalicylic acid (ASA)  
ASA 325mg loading dose should be given the 
day of index procedure and prior to placement 
of the iCAST™ RX Stent System. 
 
Thienopyridine  
The following loading dose of one of the below 
thienopyridines should be given the day of 
index procedure and prior to placement of the 
iCAST™ RX Stent System. 
       Clopidogrel: ≥ 300mg  
       Prasugrel: ≥ 60mg  
       Ticlopidine: ≥ 500mg  
 
During Procedure  IV Heparin or low molecular 
weight heparin or bivalirudin 
Per routine hospital practice 
Post Procedure  
Acetylsalicylic acid (ASA)  
At least 75-325mg per day for a minimum of 3 
months 
 
Thienopyridine  
The following maintenance dose of one of the 
below thienopyridines should be given for a 
minimum of 3 months or longer based on local 
guidelines, except when it is medically 
necessary to take subjects off therapy. 
         Clopidogrel: ≥ 75mg  
         Prasugrel: ≥ 10mg  
         Ticlopidine: ≥ 250mg (twice per day) 
 
 
 

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5.0 
STATISTICAL CONSIDERATIONS AND ANALYSIS PLAN  
5.1 
ASSUMPTION OF PRIMARY ENDPOINT RATE  
The endpoints will be tested in a sequential manner: 
 
1) Functional Endpoint 
Assessment of primary patency rate at 9-months, defined as continuous patency without 
the occurrence of a total occlusion of the original lesion, without a re-intervention to treat 
a partial or total occlusion of the stented segment, or bypass of the stented segment due to 
clinically-driven restenosis or occlusion. 
 
Followed by: 
 
2) Clinical Endpoint 
Improvement in systolic blood pressure (SBP) at 9-months as compared to baseline 
systolic blood pressure. 
 
If the null hypothesis for the functional goal is rejected at the 0.025 level of significance, the null 
hypothesis for the clinical goal will be tested at the 0.025 level.  If rejected, success will be 
declared for both Performance Goals.  Otherwise, if only the first (primary patency) null 
hypothesis can be rejected, success will be declared only for that Performance Goal.  This 
sequential approach controls the overall significance level at 0.025.  Of note, no success can be 
declared if the null hypothesis for the primary patency goal was not rejected, regardless of the 
outcome for the other Performance Goal. 
 
For the primary patency endpoint, the proportion of subjects experiencing this outcome will be 
compared to the predefined Performance Goal of 0.70. Formally, the hypothesis to be tested is: 
 
H0:  
The incidence pPP of primary patency at 9-months is less than or equal to 0.70. 
 
Ho:   pPP ≤  0.70 
 
HA:          The incidence pPP of primary patency at 9-months is greater than 0.70. 
 
HA:  pPP  > 0. 70 
 
 
The derivation of the Performance Goal is described in Section 5.2.1 Derivation of the 
Performance Goal for Patency. 
    
 

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For the SBP endpoint, the change between SBP from baseline to 9-month follow-up will be 
compared to a predefined Performance Goal of 10mmHg. Formally, the hypothesis to be tested 
is: 
 
H0:  
The mean difference between SBP at 9-months and baseline, μ∆SBP, is less than or equal 
to 10mmHg. 
Ho:   μ∆SBP  ≤  10mmHg 
 
HA:  
The mean difference between SBP at 9-months and baseline, μ∆SBP, is greater than 
10mmHg. 
 
Ho:   μ∆SBP  > 10mmHg 
 
Both primary endpoints will be tested in one-sided fashion against a significance level of 0.025; 
the primary patency endpoint will be tested using exact binomial methods and the SBP endpoint 
will be tested using a paired t-test. 
 
5.2 
SAMPLE SIZE 
For a one-sided alpha of 0.025 and desired power of 87%, sample size for the primary patency 
endpoint is established by assuming a hypothesized primary patency incidence of 0.82, which 
gives 125 evaluable subjects therefore, accounting for 10% attrition, 138 subjects are needed for 
this endpoint. At the proposed evaluable sample size of 125, no more than 27 subjects (22%) can 
fail primary patency in order to meet the endpoint hypothesis. 
 
For the endpoint of reduction in SBP, we assume an average reduction of 13.7mmHg.  Under a 
hypothesized standard deviation of 12mmHg for a difference in SBP there will be 92% power to 
meet the Performance Goal. This standard deviation is conservatively approximated based on the 
expected range of SBP at baseline of 155mmHg to 180mmHg divided by 3 and assuming a 
similar standard deviation at the 9-month follow up. A mean difference in SBP at 9-months of 
12mmHg will be required in order to reject the null hypothesis at a one-sided alpha of 0.025 at 
the proposed sample size. 
 
The primary endpoints of primary patency and reduction in SBP are powered at 87% and 92%, 
respectively, in order to maintain the overall trial power at 80% to meet both endpoints. 
 
5.2.1 DERIVATION OF THE PERFORMANCE GOAL FOR PATENCY 
The Performance Goal was derived from a thorough literature review of trials with renal 
bare metal stent placement. Trials were identified by means of a PUBMED search of the 
English-language medical literature from 1991 to 2010. When available, the following 
data were extracted: author and year of publication, number of subjects, number of 

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arteries, restenosis definition, evaluation method, duration of follow-up, and restenosis 
rate. Of the 30 articles reviewed, 9 articles were excluded from the Performance Goal 
based on the following: results from studies with data collection from the 1980’s which is 
not representative of today’s standard of care, definitions used for restenosis were outside 
of our trial design, follow-up occurred at times outside of our assessments, and results 
from studies not yet published. 
The following references were deemed relevant for the patency Performance Goal: 
 
Table 3: Derivation of Patency Performance Goal 
Author 
Year 
Number 
of 
Subjects 
Number 
of 
Arteries 
Evaluation 
Method 
Follow-up 
Time 
Restenosis 
Rate 
Rocha -Singh et al9 
2005 
208 
252 
DUS 
9 mo 
17.4% 
Laird et al39 
2010 
188 
188 
DUS 
9-12 mo 
16.8% 
Fleming et al40 
2010 
30 
66 
Angio 
6 mo 
35% 
Corriere et al41 
2009 
91 
101 
DUS 
12 mo 
26.7% 
Rocha-Singh et al2 
2008 
100 
117 
DUS 
9 mo 
21.3% 
Nolan et al42 
2005 
78 
97 
DUS 
12 mo 
25% 
Nolan et al43 
2005 
82 
96 
DUS 
12 mo 
25% 
Sapoval et al44 
2005 
52 
52 
Angio 
6 mo 
14% 
Shammas et al45 
2004 
58 
58 
DUS, 
Angio, CTa 
2-20 mo 
26% 
Lederman et al16 
2001 
300 
358 
Angio 
16 mo 
21% 
Symonides et al7 
1999 
27 
27 
DUS, Angio 
to confirm 
6 mo 
30% 
Van de Ven et al8 
1999 
42 
51 
Angio 
6 mo 
14% 
Rundback et al46 
1998 
45 
32 
Angio 
12 mo 
25% 
Tullis, et al47 
1997 
41 
52 
Angio/DUS 
12 mo 
44% 
Harden et al48 
1997 
32 
33 
Angio 
6 mo 
12% 
White et al49 
1997 
100 
133 
Angio 
6-12 mo 
19% 
Iannone et al50 
1996 
63 
86 
DUS 
12 mo 
14% 
Dorros et al51 
1995 
76 
92 
Angio 
6 mo 
25% 
Hennequin et al52 
1994 
21 
25 
Angio 
12 mo 
19% 
 
The weighted mean restenosis rate from these trials is 21.4%.  Assuming a restenosis rate 
for PTRA of 40% as noted in Carr based on the analysis of 6 trials with PTRA(1) and also 
used by Rocha-Singh,(2) a restenosis rate of 30% leading to a Performance Goal for 
primary patency set at 70%. This goal will preserve at least 50% of the difference 
between the currently available bare metal stent rate and the PTRA rate, as well as adjust 
for a lesion set with a higher percentage stenosis (80%-100%) than previous reported 
studies (50%-100%). 
 

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5.3 
ENDPOINT ANAYLSIS AND REPORTING OF RESULTS 
5.3.1 GENERAL CONSIDERATIONS 
Unless otherwise specified, the following summary statistics will be presented. For 
continuous variables, statistics will include means, standard deviations and 95% 
confidence intervals for the means when normal-distribution assumptions are not 
violated. Otherwise, medians and Interquartile Range (IQR) will be presented. 
Categorical variables will be summarized using counts and frequencies. For time-to-event 
data, Kaplan-Meier estimates at the indicated time points will be displayed along with 
95% confidence intervals.  In addition, survival curves will be constructed for all time-to-
event secondary endpoints using Kaplan-Meier methods. 
 
Statistical tests relating to the primary endpoints will be one-sided with p-values less than 
0.025 deemed significant.   
 
Statistical analyses will be conducted in Statistical Analysis System (SAS) version 9.1 or 
above (SAS Institute, Cary, N.C.) or another validated statistical software package. 
 
5.3.2 ANALYSIS POPULATIONS 
Intent-to-Treat (ITT) Analysis Set:  All subjects enrolled in the study will be included in 
the ITT analysis set. This will be the primary analysis set. 
 
Per Protocol Analysis Set:  All subjects enrolled in the study, who receive the study 
device 
as 
intended 
with 
no 
major 
protocol 
violations 
(such 
as 
stent 
placement/deployment errors) will be included in the Per Protocol analysis set.  The 
primary endpoints will be additionally tested in this analysis set. 
 
5.3.3 MISSING DATA 
Results from imputing all possible combinations of successes and failures for the missing 
data will be summarized. 
 
5.3.4 MULTIPLICITY ADJUSTMENT 
Alpha for the primary hypotheses will be controlled by testing the endpoints 
hierarchically.  Patency will be tested first followed by systolic blood pressure.  The test 
for systolic blood pressure will only be conducted if the patency Performance Goal is 
met.   
 
Two additional secondary endpoints will be evaluated hierarchically if and only if the 
primary objective is met.  In order to control alpha, the endpoint of clinically driven TLR 
will be tested as described below, followed by changes in the number or dosage of anti-
hypertensive medications as compared to baseline.   
 
 

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5.3.5 PRIMARY ENDPOINT ANALYSIS 
 
5.3.5.1 
PRIMARY PATENCY 
The primary endpoint of primary patency will be summarized using counts and 
frequencies.  An exact one-sided 95% confidence interval will be constructed and the 
upper limit compared to the Performance Goal of 70%.  A p-value for the one-sided 
test of the difference between the observed rate and the Performance Goal will be 
presented.  
 
5.3.5.2 
SYSTOLIC BLOOD PRESSURE 
The primary endpoint of SBP will be analyzed according to the Performance Goal of 
a decrease in SBP of 10mmHg. 
   
The mean difference between SBP at 9-months and baseline will be compared to a 
fixed value of 10mmHg.  The baseline SBP will be summarized for all subjects and 
for those subjects with 9-month follow-up data.  The baseline and 9-month SBP data, 
as well as the difference in baseline will be summarized with means and standard 
deviations.  A one-sided 95% confidence interval for the mean difference between 
baseline and 9-month SBP will be constructed and the limit will be compared to the 
10mmHg Performance Goal.  A p-value will be computed based on the paired t-test.    
 
5.3.6 ADDITIONAL ANALYSES 
 
5.3.6.1 
SENSITIVITY ANALYSIS 
For primary patency, a tipping point analysis will be conducted in order to assess the 
effect of missing data on the analysis. Results from imputing all possible 
combinations of successes and failures for the missing data will be summarized. 
 
For the SBP endpoint, as a best/worst case analysis, the largest/smallest drop in SBP 
seen in the complete data will be filled in for the missing values.  Summary statistics 
for the resulting mean difference and p-values from the primary hypothesis test will 
be presented.  In addition, multiple imputations will be used by substituting imputed 
SBP at 9-months based on available baseline characteristics (including baseline SBP) 
and then recalculating the mean differences, presenting summary statistics and the p-
value for the primary hypothesis. 
 
5.3.6.2 
SECONDARY ENDPOINTS ANALYSIS 
 
5.3.6.2.1 MAJOR SECONDARY ENDPOINTS 
 
5.3.6.2.1.1 
TLR 
The secondary endpoint of clinically driven TLR will be summarized using 
counts and frequencies.  An exact one-sided 95% confidence interval will be 

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constructed and the upper limit compared to the Performance Goal rate of 
8.5% as described below.  A p-value for the one-sided test of the difference 
between the observed rate and the Performance Goal will be presented.  
The Performance Goal of 8.5% was established from a review of the relevant 
literature as detailed in the following table. 
Table 4: Derivation of TLR Performance Goal 
Author 
# 
subjects 
f/u time 
TLR 
Assessment 
Subjects 
with 
TLR 
TLR 
Rocha -Singh et al9 
208 
9 mo 
9 mo 
9     
4.3% 
Laird et al39 
188 9-12 mo 
9 mo 
17     
9.0% 
Corriere et al41 
91 
12 mo 
6 mo 
10     11.0% 
Rocha-Singh et al2 
100 
9 mo 
9 mo 
8     
8.0% 
Nolan et al42 
78 
12 mo 
12 mo 
8     10.3% 
Nolan et al43 
82 
12 mo 
12 mo 
8     
9.8% 
Sapoval et al44 
52 
6 mo 
6 mo 
4     
7.7% 
Symonides et al7 
27 
6 mo 
6 mo 
8     29.6% 
Van de Ven et al8 
42 
6 mo 
6 mo 
0     
0.0% 
Hennequin et al52 
21 
12 mo 
9 mo 
4     
5.3% 
 
 
 
Weighted Average 
8.5% 
 
5.3.6.2.1.2 
CHANGES IN THE NUMBER OR DOSAGE OF ANTI-
HYPERTENSIVE MEDICATIONS 
The secondary endpoint of changes in the number or dosage of anti-
hypertensive medications as compared to baseline will be summarized using a 
shift table.  The number of patients will be compared to baseline using the 
paired McNemar's test.    
5.3.6.2.2 OTHER SECONDARY ENDPOINTS 
All other secondary endpoints will be evaluated in the ITT population using 
descriptive statistics. No formal hypothesis testing will be performed. The 
secondary endpoints will be summarized for continuous, categorical or time-to-
event data, as appropriate.   
5.3.6.3 
SUBJECT 
DISPOSITION, 
DEMOGRAPHICS 
AND 
OTHER 
BASELINE CHARACTERISTICS 
Baseline demographic and clinical variables will be summarized for both the ITT and 
Per Protocol analysis sets for continuous or categorical variables, as appropriate.  
5.3.6.4 
SITE-LEVEL POOLABILITY 
 
Poolability of the data across sites will be examined by testing the homogeneity of the 
primary endpoint results across sites using a random effects model.  If differences in 
the primary or major secondary endpoints exist, these effects will be further examined 
and results will be additionally reported by adjusting for site using a random effects 

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model.  Since there may be few patients per site and regional differences are 
expected, this analysis will be repeated for regional differences (US versus OUS). If 
heterogeneity is detected and the differences between the sites or regions can be 
attributed to specific differences in baseline characteristics, the random effects model 
will be further adjusted by these variables.  Testing will be conducted at the 
alpha=0.15 level for this analysis. 
  
5.3.6.5 
OTHER SAFETY DATA 
Concomitant medications and AEs will be summarized at each follow-up visit.  In 
addition, tables and listings will be provided. 
 
6.0 
ADVERSE EVENTS, SERIOUS ADVERSE EVENTS, AND 
 
UNEXPECTED DEVICE EFFECTS 
 
In this trial, subjects should be encouraged to report AEs spontaneously or in response to 
general, non-directed questioning.  At any time during the trial, the subject may volunteer 
information that identifies an AE.  If it is determined that an AE has occurred, the investigator 
should obtain all the information required to complete the AE on the designated eCRF. 
6.1 
DEFINITIONS 
Adverse Events (AE):  Any untoward medical occurrence observed in a patient or a clinical 
investigation subject administered an investigational product and that does not necessarily have a 
causal relationship with this treatment. An AE can therefore be any unfavorable and unintended 
sign (including any clinically significant abnormal laboratory finding), symptom, or disease 
temporally associated with the investigational intervention, whether or not considered related to 
the investigational intervention. Pre-existing conditions, which worsen during a trial, are to be 
considered AEs.   
 
Serious Adverse Event (SAE):  Any adverse experience that results in any of the following 
outcomes: 
 Death 
 Is life-threatening  
 Subject hospitalization or prolongation of existing hospitalization 
 A persistent or significant disability or incapacity 
 Congenital anomaly or birth defect 
 Important medical events that may not be immediately life-threatening or result in death 
or hospitalization, but may jeopardize the subject or may require intervention to prevent 
one of the outcomes listed in the definition above. 
 
Unanticipated Adverse Device Effect (UADE):  Any serious adverse effect on health or safety, 
or any life-threatening problem or death caused by, or associated with, a device, if that effect, 

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problem, or death was not previously identified in nature, severity, or degree of incidence in the 
Investigational Plan or IFU, or any other unanticipated serious problem associated with a device 
that relates to the rights, safety, or welfare of subjects. A list of anticipated AEs is provided 
below. 
 
6.1.1 ANTICIPATED AEs  
Based on the literature and on clinical and commercial experience with implantation of a 
covered stent in human arteries, Table 5: Anticipated AEs, includes anticipated AEs that 
have been identified as possible complications:  
 
 
Table 5: Anticipated AEs 
o Abdominal Pain 
o Abscess 
o Acute or sub-acute thrombosis 
o Acute myocardial infarction 
o Allergic reaction to stainless steel, drugs, 
contrast agent, or anti-platelet agents 
o Aneurysm 
o Arrhythmias, including Ventricular 
Fibrillation (VF) and Ventricular 
Tachycardia (VT) 
o Arteriovenous (AV) fistula 
o Bowel infarct 
o Death 
o Dialysis 
o Emboli (air, tissue, or thrombotic) resulting 
in tissue ischemia or infarction 
o Emergency surgery to correct vascular 
complications 
o Extremity ischemia/amputation 
o Fever 
o Hemorrhage  
o Hematoma 
o Hypotension or hypertension 
o Inadequate implantation or Intimal trauma 
o Inadvertent exclusion of branch or 
accessory vessel 
o Incision site pain or infection 
o Injury, dissection, perforation, or rupture 
of the vessel 
o Kidney infarct 
o Myocardial infarction or ischemia 
o Nephrectomy 
o Pseudo-aneurysm formation 
o Pyrogenic reaction 
o Renal insufficiency or failure  
o Restenosis of stented lesion 
o Sepsis/infection 
o Stent embolization 
o Stent migration/stent misplacement 
o Stroke or other cerebrovascular accident 
o Thromboembolic event 
o Tissue necrosis or ulceration 
o Total occlusion 
o Vessel spasm 
 
6.2 
DEVICE FAILURES, MALFUNCTIONS AND NEAR INCIDENTS 
Investigators are instructed to report all possible device failures, malfunctions or near incidents 
observed during the course of the trial, to Atrium.  In addition, these incidents will be 
documented in the eCRF provided as follows: 
 
 Device Failure:  A device failure has occurred when the device is used in compliance 
with the IFU, but does not perform as described in the IFU and also negatively impacts 
treatment of the trial subject.  

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 Device Malfunction:  A device malfunction occurs when an unexpected change to the 
device that is contradictory to the IFU is observed, which may or may not affect device 
performance. 
 Device Misuse:  Any use of the investigational device by an investigator that is 
contradictory to the application described in the IFU will be categorized as device 
misuse. 
6.3 
DOCUMENTATION 
All AEs must be listed in the subject’s source record, transcribed onto on the appropriate eCRF, 
and will be characterized by the following criteria:  
 Intensity or Severity 
 Relatedness 
 Outcome 
 Treatment or Action Taken 
 Expectedness 
 
All AEs (serious and non-serious) will be recorded upon completion of the ICF process through 
the 9-month follow-up visit. Thereafter, only SAEs (for example, those that result in 
hospitalization, permanent disability, death, or threat of death) will be recorded. All SAEs will be 
reported to the CEC and DSMB.  
 
6.3.1 INTENSITY OR SEVERITY 
The severity of the AE or SAE should be based on the following categories: 
 Mild:  An AE that is noticeable to the subject and may require additional therapy 
and is resolved without treatment and with no sequelae. 
 Moderate:  An AE that interferes with the subject’s activities and requires 
intervention or additional therapies. 
 Severe:  An AE that is intolerable, or necessitates additional therapy or places the 
subject at immediate risk of harm. 
 
6.3.2 RELATEDNESS 
The Principal Investigator (PI) will evaluate if the AE or SAE is related to the 
investigational device.  Relatedness is defined in the following manner: 
 Not related: The PI has determined that the complication is not related to the trial 
device. 
 Unlikely: The current state of knowledge indicates that a relationship to the use of 
investigational device is unlikely. 
 Possibly or Probably:   The PI has determined that the event has a reasonable 
relationship to the use of the investigational device.  
 Definite: The PI has determined that the complication is related to the 
investigational device. 

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6.3.3 OUTCOME 
The clinical outcome of the AE or SAE will be characterized as follows: 
 Death:  The SAE eCRF must be completed for this outcome. 
 Recovered without Sequelae:  Subject returned to baseline status. 
 Not Yet Recovered:  Subject did not recover and symptoms continue. 
 Recovered with Sequelae: Subject has recovered but with clinical sequelae from 
the event. 
 Recovered without Sequelae:  Subject returned to baseline status. 
 Unknown: Subject outcome is unknown. 
 
6.3.4 TREATMENT OR ACTION TAKEN 
AEs or SAEs will result in: 
 Interventional Treatment:  Surgical, percutaneous or other procedure. 
 Medical Treatment:  Medication dose reduction/interruption or discontinuation, or 
medication initiated for event. 
 None: No action is taken. 
 
6.3.5 EXPECTEDNESS 
 Anticipated: Any AE previously identified as a possible complication in the 
clinical protocol per Section 6.1.1, the IFU, labeling, or published literature. 
 Unanticipated: Any AE not previously identified as a possible complication in the 
clinical protocol per Section 6.1.1, the IFU, labeling, or published literature. 
 
6.4 
EXPEDITED REPORTING OF SAEs AND UADEs 
The procedure for reporting any unexpected and related SAEs or UADEs is as follows: 
 Report any unexpected and related SAEs or UADEs to Atrium or its designated CRO 
within 1 business day of knowledge of event by completing the appropriate eCRF forms. 
 Report any SAEs or UADEs to the IRB/EC according to the investigational site’s 
IRB/EC procedures. 
 Submit physician/nurse notes or discharge summaries related to the reported event, as 
requested. 
 Report of a subject death must be submitted along with a brief statement of the pertinent 
details and the death records/certificate or autopsy report, if available/performed. 
 
Atrium or its designated CRO will forward site reported unexpected and related SAEs and all 
UADEs to the regulatory authorities and investigational sites within 10 working days of its 
receipt.  The investigational site will be responsible to forward this report to its IRB/EC.   
 

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7.0 
TRIAL COMMITTEES 
 
7.1 
DATA SAFETY MONITIORING BOARD (DSMB) 
The Data Safety Monitoring Board (DSMB) is composed of at least three members which 
include physicians with specialization in the field of this trial and a biostatistician, and are 
independent and not directly involved in the conduct of the trial.  The DSMB will review the trial 
on a periodic basis to be defined in the Charter.  
 
Based on the safety data, the DSMB may recommend to Atrium to modify or stop the trial.  All 
final decisions, however, regarding trial modifications, rest with Atrium.  No formal statistical 
rule for stopping the trial will be defined in this trial and no formal interim analysis is planned.   
 
7.2 
CLINICAL EVENTS COMMITTEE (CEC) 
The Clinical Events Committee (CEC) is made up of physicians with specialization in the field 
of this trial who are not participants in the trial.  The CEC is charged with the development of 
specific criteria used for adjudication of clinical events related to the primary endpoints in the 
trial. 
 
At the onset of the trial, the CEC will develop a CEC Charter which will describe explicit rules 
outlining the minimum amount of data required, and the algorithm followed in order to classify a 
trial endpoint related clinical event.  The CEC will meet regularly (at a minimum of once per 
year) to review and adjudicate trial endpoint related clinical events in which the required 
minimum data is not available. The CEC will also review and rule on all deaths that occur 
throughout the trial. 
 
Once the specific criteria for clinical events and endpoints are established, the CEC will be 
responsible for adjudicating all clinical events when all necessary data are available.   
 
8.0 
 INVESTIGATOR RESPONSIBILITIES 
 
The Investigator will ensure the trial will be performed in accordance with the basic principles of 
the Declaration of Helsinki, ICH E6 Good Clinical Practice (GCP): Consolidated Guidelines, 
ISO 14155, and any applicable local or governmental regulations.  It is the responsibility of each 
Investigator to provide the current protocol and relevant training to all other staff responsible for 
trial conduct. 
8.1 
TRAINING 
The training of appropriate investigational site personnel will be the responsibility of the 
Sponsor, CRO, and PI.  The Investigator is responsible for ensuring that his/her staff conduct the 
trial according to the protocol.  The Investigational Plan, instructions on data collection, 

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schedules for follow-up with the investigational site coordinators, and regulatory requirements 
will be addressed at the initiation visit. At this visit, Atrium or its designated CRO will also 
present a formal training session to investigational site personnel that will include review of the 
device IFU. 
8.2 
PROTOCOLS AND AMENDMENTS 
The protocol and any protocol amendments must be signed and dated by the Investigator and 
approved by the IRB/EC prior to implementation. No changes to the protocol may be made 
without the agreement Atrium or its designated CRO. Any amendment to the original protocol 
will be signed by both parties and submitted to the IRB/EC for approval or notification. 
Documentation of all study amendment activity should be forwarded to Atrium or its designated 
CRO.  
8.3 
INFORMED CONSENT 
Prior to participation in the trial, the IRB/EC approved written ICF should be signed and 
personally dated by the subject or his/her legal representative, and by the person who conducted 
the informed consent discussion (investigator or designee).  If the subject or his/her legal 
representative is unable to read the ICF, a witness should be present during the entire informed 
consent discussion.  After the ICF is read to the subject and signed by the subject or his/her legal 
representative, the witness should also sign the ICF, attesting that informed consent was freely 
given by the subject or his/her legal representative.  The informed consent process should be 
documented in each subject’s record.   
 
The subject or his/her legal representative must receive a copy of the signed and dated ICF. The 
consent form should be updated or amended whenever new information becomes available that 
may be relevant to the subject. 
8.4 
SOURCE DOCUMENTATION REQUIREMENTS 
Regulations require that Investigators maintain information in the trial subject’s medical records 
which corroborate data collected on the eCRF.  In order to comply with these regulatory 
requirements, the investigator will maintain and make available as required by monitors, Atrium 
or its designated CRO, and/or its regulatory inspectors the following information that includes 
but is not limited to: 
 Signed ICFs and associated documents. 
 Medical history/physical condition of the trial subject before involvement in the trial 
sufficient to verify protocol entry criteria. 
 Dated and signed notes in the subject’s medical record on the day of entry into the trial 
that identify: the subject’s date of entry into the trial, the clinical site, subject’s assigned 
number, and a statement that ICF was obtained. 
 Dated and signed notes for each trial subject visit with reference to the eCRFs for further 
information, if appropriate (for specific results of procedures and exams). 

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 Description of device implantation procedure (material used, drugs administered during 
the procedure, date, time duration, angiographic, US and clinical findings, etc.). 
 Notations on abnormal lab results and their resolution. 
 Dated printouts or reports of special assessments, i.e. angiography, echo doppler, CT, X-
rays, laboratory tests. 
 AE reporting and follow-up of the AEs (minimally event description, severity, onset date, 
duration, relation to trial device, outcome and treatment for AEs). 
 Notes regarding concomitant medications taken during the trial (including start and stop 
dates). 
 Trial subject’s condition upon completion of or withdrawal from the trial. 
8.5 
PROTOCOL DEVIATIONS 
A protocol deviation is defined as an event where the Investigator or investigational site 
personnel did not conduct the trial according to the protocol.  Examples of deviations may 
include, enrollment of a trial subject who does not meet all of the inclusion/exclusion criteria 
specified in the protocol and missed trial visits.   
 
Atrium will report all deviations annually as part of the IDE annual report to the appropriate 
regulatory authorities. 
 
Deviations shall be reported to Atrium or its designated CRO regardless of whether medically 
justifiable or done to protect the subject.  Non-subject specific deviations, (e.g. unauthorized use 
of an investigational device outside the trial, unauthorized use of an investigational device by a 
physician who has not signed an investigator agreement, etc.), will also be reported to Atrium or 
its designated CRO in writing.  Investigators will also adhere to procedures for reporting 
protocol deviations to their IRB/EC in accordance with their specific IRB/EC reporting policies 
and procedures.  Regulations require that Investigators maintain accurate, complete and current 
records, including documents showing the dates of and reasons for each deviation from the 
protocol.  
8.6 
DEVICE ACCOUNTABILITY 
The Investigator must ensure that the investigational product is used only in accordance with the 
approved protocol and administered only to subjects under the investigator’s supervision or 
under the supervision of a sub-investigator. It is the responsibility of the Investigator to maintain 
adequate accountability records of the receipt and disposition of all investigational devices. At 
the trial closeout visit, the Investigator must return to Atrium or its designated CRO, any unused 
devices and a copy of the completed device inventory.  The Investigator’s copy of the device 
reconciliation report must document any unused devices that have been returned to Atrium or its 
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8.7 
MONITORING 
Atrium or its designated CRO will conduct investigational site monitoring visits to ensure that all 
Investigators conduct the trial in compliance with the protocol and Investigators’ agreements.  
The investigational site will receive notification prior to each monitoring visit during the course 
of the trial.  It is expected that the Investigator and other appropriate staff are available on the 
day of the visit in case any questions might arise.   
 
The progress of the trial will be monitored by: 
 Ensuring the completed eCRF matches the source documents, and resolution of any 
discrepancies.   
 Periodic on-site and off-site review. 
 Frequent telephone or electronic communications between the Investigator and site 
monitor’s. 
 Review of eCRF and clinical records/source documents. Direct access to complete source 
documents must be made available during monitoring visits for verification of case report 
form data. 
 
Periodic monitoring visits will be made at all active investigational sites throughout the clinical 
trial to assure that Investigator obligations are fulfilled and all applicable regulations and 
guidelines are being followed.  These visits will assure that the facilities are still acceptable, the 
protocol is being followed, the IRB/EC has been notified of approved protocol changes as 
required, complete records are being maintained, appropriate and timely reports have been made 
to Atrium or its designated CRO and the IRB/EC, device and device inventory are controlled, 
and the Investigator is executing all agreed activities. 
 
Atrium or its designated CRO will retain the right to remove either the Investigator or the 
investigational site from the trial for issues of non-compliance with the protocol or regulatory 
requirements.  Atrium’s designated CRO will fulfill the responsibilities identified in their SOPs.   
 
Atrium or its designated CRO will review significant new information, including UADEs and 
ensure that such information is provided to the appropriate regulatory authorities, Investigators, 
and to all reviewing IRBs/ECs. 
8.8 
AUDITS 
On one or more occasions, the investigational site may be inspected or audited by Atrium, Food 
and Drug Administration (FDA), other local regulatory agency, or a third party. The Investigator 
may be informed in advance of this visit. Atrium and/or auditors may request direct access to all 
study records including source documents for inspection and copying, in keeping with country 
regulations.  In the event of an audit by regulatory agency, the Investigator will make all 
pertinent records available including source documentation for inspection and will immediately 
notify Atrium or its designated CRO upon notification of any regulatory agency inspections.  

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8.9 
RECORD RETENTION 
The Investigator will maintain all essential trial documents and source documentation, in original 
format, that support the data collected on the study subjects in compliance with the ICH/GCP 
guidelines. Documents must be retained for at least 2 years after the last marketing application 
approval or until at least 2 years have elapsed since the formal discontinuation of the clinical 
investigation of the product.  These documents will be retained for a longer period of time by 
agreement with Atrium or in compliance with other regulatory requirements.  When these 
documents no longer need to be maintained, it is Atrium’s responsibility to inform the 
Investigator.  The Investigator will take measures to ensure that these essential documents are 
not accidentally damaged or destroyed.  If for any reason the Investigator withdraws 
responsibility for maintaining these essential documents, custody must be transferred to an 
individual who will assume responsibility. Atrium must receive written notification of this 
custodial change.  
8.10 
PUBLICATION POLICIES 
At the conclusion of the ARTISAN trial, a multi-center manuscript will be prepared for 
publication in a reputable scientific journal.  The publication of the principal results from any 
single investigational site experience within the trial is not allowed until the preparation and 
publication of the multi-center results.  Exceptions to this rule require the prior approval of 
Atrium.  The analysis of pre-specified and non pre-specified endpoints will be performed by a 
statistician.  Such analyses, as well as other proposed investigations will require the approval of 
Atrium.  For purposes of timely abstract presentation and publication, the writing of these 
secondary publications will be delegated to the appropriate principal authors, and final analyses 
and manuscript review for all multi-center data will require the approval of Atrium. 
 
9.0 
ROLE OF TRIAL SPONSOR 
 
As the Sponsor of this clinical trial, Atrium has the overall responsibility for the conduct of the 
trial, including assurance that the trial meets and is conducted within the regulatory requirements 
specified by each reviewing regulatory authority. In this trial, Atrium will have certain direct 
responsibilities and will delegate other responsibilities to other designees.  Atrium or its 
designated CRO will ensure adherence to the Sponsor general duties, selection of Investigators, 
monitoring, supplemental applications, maintaining records, and submitting reports. 
9.1 
GENERAL DUTIES  
Atrium’s general duties also include submission of application to the appropriate regulatory 
authorities and obtaining overall regulatory approval.  
 
Atrium or its designated CRO is responsible for ensuring the ICF is obtained and proper 
investigational site monitoring is performed, providing quality data that satisfies regulations and 
informing Investigators of UADE events and deviations from the protocol, as appropriate.  

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Atrium or its designated CRO will prepare written reports, a final report, and will coordinate data 
collection and transfer with the core laboratory.  
9.2 
CRITERIA FOR SUSPENDING/TERMINATING AN 
INVESTIGATIONAL SITE 
Atrium reserves the right to stop the screening and enrollment of subjects at any investigational 
site at any time for any of the following reasons: 
 Noncompliance to GCP/ICH or protocol 
 Failure to obtain IRB/EC approval 
 Failure to enroll subjects 
 Multiple and/or severe protocol deviations 
 Inaccurate or incomplete data 
 Unsafe or unethical practices 
 Safety or performance considerations 
 Administrative decision 
 
NOTE: If an investigational site is suspended or terminated, AE assessment and reporting (as 
outlined in this protocol) will continue for all subjects who received an investigational product.  
  
10.0 SUBJECT CONFIDENTIALITY 
 
Subject confidentiality will be maintained throughout the clinical trial in a way that assures that 
data can always be tracked back to the source data.  For this purpose, a unique subject 
identification code (i.e. assigned subject number and subject initials) will be used that allows 
identification of all data reported for each subject.  
Data relating to the trial might be made available to third parties (for example in case of an audit 
performed by regulatory authorities) provided the data are treated confidential and that the 
patient’s privacy is guaranteed. 
 
The Investigator will grant monitor(s) and auditor(s) from Atrium or its designated CRO and 
regulatory authorities access to the subject’s original medical records for verification of data 
gathered on the eCRF and to audit the data collection process. The subject’s confidentiality will 
be maintained and will not be made publicly available to the extent permitted by applicable laws 
and regulations.  
 
“Protected Health Information” will be maintained in compliance with the Health Insurance 
Portability and Accountability Act of 1996 (HIPAA) Privacy rule, where applicable. 
 

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11.0 RISKS TO SUBJECTS 
11.1 
HUMAN SUBJECTS INVOLVEMENT AND CHARACTERISTICS 
This trial will enroll 138 adults with de novo atherosclerotic renal artery disease. The 
inclusion and exclusion criteria are described in Sections 3.2 and 3.3.  Vulnerable 
populations, specifically prisoners, institutionalized individuals will not be targeted for 
recruitment.  Pregnant subjects are excluded because this product has not been investigated in 
this population and the risk to the fetus is unknown.   
11.2 
POTENTIAL RISKS 
There may be a direct benefit to the subject as the iCAST™ RX Stent System allows for 
dilatation of the renal artery. This stent has the potential benefits of less injury due to the low 
profile delivery system and the metal stent is completely encapsulated with the ePTFE covering 
making it more stable and accurately deployed than other balloon expandable stents of similar 
diameters.  
 
There are risks for participants in this trial. Potential risks have been minimized by establishing 
strict inclusion/exclusion criteria to ensure appropriate subjects participate in the trial.  
Additionally, all enrolling investigators will be instructed on appropriate patient selection, in an 
effort to minimize the risk of recruiting patients who are found to be ineligible for trial 
participation.    
 
To minimize the risk of the invasive assessment and the stent procedure, investigators will 
perform angiography and stent placement based on:  current medical license, privileges to 
perform these services at their treatment center, board certification, or equivalent experience.  
Appropriate angiographic technique principles will be utilized to expose subjects to the least 
amount of contrast dye and radiation while providing high resolution angiograms.   
 
Some risks associated with surgery include but are not limited to adverse reactions to anesthesia, 
DVT, neurological cardiac or respiratory deficit, infection, continuation and/or worsening of the 
original diagnosis and death.  However, it should be noted that the risks of trial participation are 
not materially different than those entailed by an individual who undergoes a stent procedure 
with an approved stent. Table 6: Potential AEs Related to Stent Placement outlines possible AEs 
related to stent placement: 
 
 
 
 
 
 
 

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Table 6: Potential AEs Related to Stent Placement 
Adverse Event 
Anticipated 
Incidence 
Abdominal Pain 
< 0.1% 
Abscess 
< 0.1% 
Acute or sub-acute thrombosis 
< 0.1% 
Acute myocardial infarction 
< 0.1% 
Allergic reaction to stainless steel, drugs, contrast agent, or anti-platelet 
agents 
< 0.1% 
Aneurysm 
< 2% 
Arrhythmias, including VF and VT 
< 0.1% 
Arteriovenous (AV) fistula 
< 2% 
Bowel infarct 
< 1% 
Death 
< 6% 
Dialysis 
< 5% 
Emboli (air, tissue, or thrombotic) resulting in tissue ischemia or infarction 
< 4% 
Emergency surgery to correct vascular complications 
< 3% 
Extremity ischemia/amputation 
< 0.1% 
Fever 
< 0.1% 
Hemorrhage  
< 5% 
Hematoma 
< 4% 
Hypotension or hypertension 
< 17% 
Inadequate implantation or Intimal trauma 
< 5% 
Inadvertent exclusion of branch or accessory vessel 
< 10% 
Incision site pain or infection 
< 0.1% 
Injury, dissection, perforation, or rupture of the vessel 
< 2% 
Kidney infarct 
< 0.1% 
Myocardial infarction or ischemia 
< 1% 
Nephrectomy 
< 2% 
Pseudo-aneurysm formation 
< 1% 
Pyrogenic reaction 
< 0.1% 
Renal insufficiency or failure 
< 6% 
Restenosis of stented lesion 
< 21% 
Sepsis/infection 
< 0.1% 
Stent embolization 
< 0.1% 
Stent migration/stent misplacement 
< 1% 
Stroke or other cerebrovascular accident 
< 2% 
Thromboembolic event 
< 1 % 
Tissue necrosis or ulceration 
< 0.1% 
Total occlusion 
< 2% 
Vessel spasm 
< 0.1% 
 
 

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APPENDIX 1: LIST OF ABBREVIATIONS  
ACC 
 
 
 
American College of Cardiology 
ACE 
 
 
 
Angiotensin Converting Enzyme 
 
 
 
AE 
 
 
 
Adverse Event 
AHA 
 
 
 
American Heart Association 
ARAS  
 
 
Atherosclerotic Renal Artery Stenosis 
ARB 
 
 
 
Angiotensin Receptor Blocking agent 
ASA 
 
 
 
Acetylsalicylic Acid 
AV 
 
 
 
Arteriovenous 
CEC 
 
 
 
Clinical Events Committee 
CFR 
 
 
 
Code of Federal Regulations 
CHD 
 
 
 
Coronary Heart Disease 
CRO 
 
 
 
Contract Research Organization 
CTa 
 
 
 
Computed Tomography angiogram 
DSMB  
 
 
Data Safety Monitoring Committee 
DUS 
 
 
 
Duplex Ultrasound 
EC 
 
 
 
Ethics Committee 
eCRF  
 
 
Electronic Case Report Form 
eGFR  
 
 
Estimated glomerular filtration rate 
ePTFE  
 
 
expanded Polytetraflouroethylene 
FDA 
 
 
 
Food and Drug Administration 
FFR 
 
 
 
Fraction Flow Reserve 
GCP 
 
 
 
Good Clinical Practice 
HIPAA  
 
 
Heath Information Portability and Accountability Act 
ICF 
 
 
 
Informed Consent Form 
ICH 
 
 
 
International Conference of Harmonisation 
IFU 
 
 
 
Instructions for Use 
IQR 
 
 
 
Interquartile Range 
IRB 
 
 
 
Institutional Review Board 
ITT 
 
 
 
Intent-to-Treat 
MAE  
 
 
Major Adverse Event 
MI 
 
 
 
Myocardial Infarction 
MRa 
 
 
 
Magnetic Resonance Angiogram 
NIH 
 
 
 
National Institutes of Health 
PSV 
 
 
 
Peak Systolic Velocity 
PTA 
 
 
 
Percutaneous Balloon Angioplasty 
PTRA  
 
 
Percutaneous Transluminal Renal Angioplasty 
PTRAS  
 
 
Percutaneous Transluminal Renal Angioplasty with Stenting 
QVA 
 
 
 
Quantitative Vascular Analysis 
RAR 
 
 
 
Renal Aortic Ratio 
RAS 
 
 
 
Renal Artery Stenosis 
SAE 
 
 
 
Serious Adverse Event 
SAS 
 
 
 
Statistical Analysis System 
SBP 
 
 
 
Systolic Blood Pressure 
SOP(s)  
 
 
Standard Operation Procedure(s) 
TIA 
 
 
 
Transient Ischemic Attack 
TLR 
 
 
 
Target Lesion Revascularization 
UADE  
 
 
Unanticipated Adverse Device Effect 
VF 
 
 
 
Ventricular Fibrillation  
VT 
 
 
 
Ventricular Tachycardia 
 
 

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APPENDIX 2: DEFINITIONS 
 
ADVERSE EVENT 
Any untoward medical occurrence observed in a 
patient or a clinical investigational subject. This 
definition does not imply that there is a relationship 
between the AE and the device under investigation. 
An AE can therefore be any unfavorable and 
unintended sign (including any clinically significant 
abnormal laboratory finding), symptom, or disease 
temporally associated with the investigational 
intervention, whether or not considered related to the 
investigational intervention. Pre-existing conditions, 
which worsen during a trial, are to be considered 
AEs.   
 
DE NOVO LESION 
A lesion in a native vessel that has not been 
previously treated. 
 
DISSECTION 
Renal artery dissections are stenotic or occlusive 
lesions most often observed in hypertensive patients 
with underlying atherosclerosis or fibromuscular 
disease. 
Acute 
dissections 
may 
present 
spontaneously, as a complication of diagnostic or 
therapeutic angiography or as an agonal event 
associated with overwhelming systemic illness. 
Chronic dissections may produce renovascular 
hypertension or be entirely asymptomatic. 
 
 
DISTAL EMBOLIZATION 
 
Free flowing blood clot or thrombus material located 
in the circulation distal to the treated occlusion.  
 
DUAL ANTI-PLATELET 
THERAPY 
The use of thienopyridines in combination with 
aspirin therapy. 
 
EMBOLI 
Something that blocks the flow of blood in a vessel. 
It may be a gas bubble, a blood clot, a fat globule, a 
mass of bacteria, or other foreign body that usually 
forms elsewhere and travels through the circulatory 
system until it lodges in the vasculature. 
 
 

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ESTIMATED GLOMERULAR 
FILTRATION RATE  
A measure of kidney function calculated based on 
the Cockcroft-Gault equation: 
 
Male: 
eGFR(mL/min) = (140 - age) x weight (kg)/72 x SCr) 
 
Female: 
eGFR(mL/min) = (140 - age) x weight (kg) x 0.85 / 
72 x SCr)  
 
           SCr: Serum creatinine, mg/mL 
 
FIBROMUSCULAR DYSPLASIA 
Abnormal cellular development or growth in the 
walls of one or more arteries in the body; most 
commonly the renal arteries. As a result of abnormal 
cell development stenosis may develop in these 
arteries. 
FLASH PULMONARY EDEMA 
A rapid onset pulmonary edema, most often 
precipitated by acute MI or mitral regurgitation, but 
can be caused by aortic regurgitation, heart failure, 
or almost any cause of elevated left ventricular 
filling pressures.  
 
 
HEMATOMA/HEMMORRHAGE 
 
A swelling or collection of blood, usually clotted, in 
an organ, space, tissue, or access site due to a break 
in the wall of a blood vessel. It could also be 
bleeding into an extravascular space which could be 
outside the body. 
 
HYPERTENSIVE EMERGENCIES 
Hypertensive emergencies encompass a spectrum of 
clinical presentations in which uncontrolled BPs lead 
to progressive or impending organ damage.  
 
 
MAJOR ADVERSE EVENTS  
Procedure-related events inclusive of: 
 Procedure- or device-related death 
 Q-Wave MI  
 Clinically driven TLR 
 Significant embolic events  
 
 

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MAXIMUM TOLERABLE DOSE 
The highest dose of treatment that will produce the 
desired effect without unacceptable toxicity.  
NEW YORK HEART 
ASSOCIATION CLASSIFICATION 
Class I: The subject has cardiac disease but without 
resulting limitations of ordinary physical activity. 
Ordinary physical activity (i.e., walking several 
blocks or climbing stairs) does not cause undue 
fatigue, palpitation, dyspnea, or anginal pain. 
Limiting symptoms may occur with marked 
exertion. 
 
Class II:  The subject has cardiac disease resulting in 
slight limitation of ordinary physical activity. 
Subject is comfortable at rest. Ordinary physical 
activity such as walking more than two blocks or 
climbing more than one flight of stairs results in 
limiting 
symptoms 
(i.e., 
fatigue, 
palpitation, 
dyspnea, or anginal pain). 
 
Class III: The subject has cardiac disease resulting in 
marked limitation of physical activity. Subject is 
comfortable at rest. Less than ordinary physical 
activity such as walking one of two blocks or 
climbing one flight of stairs causes fatigue, 
palpitation, dyspnea, or anginal pain. 
 
Class IV: The subject has dyspnea at rest that 
increases with any physical activity. Subject has 
cardiac disease resulting in inability to perform any 
physical activity without discomfort. Symptoms of 
cardiac insufficiency or anginal syndrome may be 
present even at rest. If any physical activity is 
undertaken, discomfort is increased.  
 
Q-WAVE MYOCARDIAL 
INFARCTION 
The diagnosis of MI will be made on the basis of 
clinical information available from hospitalization 
(discharge summaries, laboratory data, ECG) and 
will require an appropriate clinical history consistent 
with acute MI. 
 
 
 

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PATENCY 
Defined and categorized as: 
 
Primary: continuous patency without the occurrence 
of a total occlusion of the original lesion, without a 
re-intervention to treat a partial or total occlusion of 
the stented segment, or bypass of the stented 
segment due to clinically-driven restenosis or 
occlusion. 
 
Secondary:  any procedure that restores patency after 
occlusion.  
 
PERFORATION 
The complete penetration of the wall of renal artery; 
this specifically refers to accidental or pathologic 
perforation, rather than intentional penetration 
during surgery. 
PRIMARY STENTING 
Stent placement without prior PTRA, an initial 
attempt at balloon dilatation, or after intentionally 
undersized pre-dilatation solely for the purpose of 
facilitating stent positioning. 
PROCEDURAL SUCCESS 
Technical success without the occurrence of MAE 
prior to hospital discharge. 
 
RESISTANT HYPERTENSION 
Failure to achieve goal BP (or SBP ≥ 155mmHg) in 
patients who are adhering to full doses of ≥ 3 anti-
hypertensive medications from at least 3 classes of 
drugs, one of which must be a diuretic. 
 
RESTENOSIS 
Recurrent stenosis 
≥ 
60% 
diameter luminal 
narrowing or recurrent 
translesional 
gradient, 
observed post-procedure as determined by the core 
laboratory. Restenosis is initially assessed by DUS 
and confirmation of percent diameter stenosis is 
made by a contrast angiography. 
 
RESTENOTIC LESION 
A lesion in the vessel segment that has undergone a 
prior percutaneous treatment.  
 
 

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SERIOUS ADVERSE EVENT 
Any adverse experience that results in any of the 
following outcomes: 
 Death 
 Is life-threatening  
 Subject hospitalization or prolongation of 
existing hospitalization 
 A persistent or significant disability or 
incapacity 
 Congenital anomaly or birth defect 
 Important medical events that may not be 
immediately life-threatening or result in 
death or hospitalization, but may jeopardize 
the subject or may require intervention to 
prevent one of the outcomes listed in the 
definition above. 
 
SIGNIFICANT EMBOLIC EVENTS 
Unanticipated kidney/bowel infarct clinically driven 
by symptoms of abdominal or back pain and 
confirmed with CT scan or open surgery, lower 
extremity ulceration or gangrene, or kidney failure. 
 
STENT THROMBOSIS 
Angiographic thrombus or sub-acute closure within 
the stented vessel.  
 
SYSTOLIC HEART FAILURE 
Heart failure with ejection fraction < 30% and/or 
hospitalization requiring intubation and ventilation 
support for this diagnosis within the previous 90 
days. 
 
TARGET LESION 
REVASCULARIZATION 
Clinically-Driven TLR - TLR (percutaneous 
balloon angioplasty (PTA), bare metal stent or repeat 
covered stent deployment) due to documented 
recurrent hypertension from 30 days post-procedure 
level and/or deterioration in renal function from 
baseline value associated with angiographic core 
laboratory adjudication of a ≥ 60% diameter covered 
stent restenosis. 
 
Incidental TLR – TLR not meeting the definition of 
a clinically driven TLR. 

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TECHNICAL SUCCESS 
Successful delivery and deployment of the iCAST™ 
RX Stent System with ≤ 30% residual stenosis after 
stent deployment (including post-dilatation) assessed 
via quantitative vascular analysis (QVA) by an 
independent core laboratory.  
 
TRANSIENT ISCHEMIC ATTACK 
An attack where a person has stroke-like (“mini-
stroke”) symptoms for up to 1 - 2 hours; these 
attacks are often considered a warning sign that a 
true stroke may happen in the future if something is 
not done to prevent it. 
 
TOTAL OCCLUSION 
A complete obstruction or a closure of a passageway 
or vessel. 
 
UNANTICIPATED ADVERSE 
DEVICE EFFECT 
Any serious adverse effect on health or safety, or 
any life-threatening problem or death caused by, or 
associated with, a device, if that effect, problem, or 
death was not previously identified in nature, 
severity, or degree of incidence in the Investigational 
Plan or IFU, or any other unanticipated serious 
problem associated with a device that relates to the 
rights, safety, or welfare of subjects. 
 
UNANTICIPATED 
KIDNEY/BOWEL INFARCT 
Clinically driven by symptoms of abdominal or back 
pain and confirmed with CT scan or open surgery. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

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APPENDIX 3: METHODOLOGY FOR OFFICE-BASED BP 
MEASUREMENT 
 
The following techniques for blood pressure determination have been proposed by the AHA and 
represent the current gold standard.(37, 53) 
 
Blood pressure must be measured with certified, calibrated, and validated equipment.  The size 
of the bladder within the blood pressure cuff must encircle at least 80% of the arm.  Subjects 
should be seated in a chair with their backs supported and their arms bared and supported at heart 
level with feet flat on the ground.  Subjects should refrain from exercise, smoking or caffeine 
ingestion for 30 minutes before blood pressure measurement, and measurement should begin 
after at least 5 minutes of rest (seated comfortably as above). Subjects should also have emptied 
their bladder prior to obtaining the measurement as a full bladder can affect the reading.  
 
 If necessary, blood pressure may be measured in the supine or reclining position.  
However, the subject should then be in the same position for subsequent 
measurements. 
 
 Both systolic and diastolic blood pressure should be recorded, with the first 
appearance of sound used to define systolic blood pressure and the disappearance of 
sound used to define diastolic blood pressure. 
 
 A minimum of three (3) readings separated by 2 minutes should be averaged.  If the 
first 3 readings differ by > 5mmHg, additional readings should be obtained and 
averaged. Blood pressure should be measured in both arms, and the higher value 
obtained should be used.  
 
 Initial blood pressure should be measured in both arms, to identify which has the 
higher reading.  From that point on, the arm with the higher reading becomes the “BP 
arm” for the remainder of the trial. For consistency, the site of blood pressure 
measurement should be recorded, and follow-up pressures should be maintained from 
the same arm.  The appropriately sized blood pressure cuff must again be used, and 
the site used must be well documented for future examinations. 

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                   Page 58 of 61 
iCAST™ RX-ARAS-001 
 
APPENDIX 4: SCHEDULE OF EVENTS 
 
(-14)-Days 
(Medical 
Documentation 
Screening 
period) 7 
 
Prior to 
Procedure 
(-7)-Days7 
 
 
 
 
 
Prior to 
Procedure 
Day 0 
 
 
 
 
 
 
Procedure 
30-Days 
(+14/-7 Days) 
 
 
 
 
Office          
Visit 
6-Months 
(+/-30 Days) 
 
 
 
 
Phone 
Call 
9-Months 
(+/-30 Days) 
 
 
 
 
Office 
Visit 
12-Months  
(+/- 30 Days) 
 
 
 
 
Office 
Visit 
 18-Months 
(+/-30 Days) 
 
 
 
 
Phone 
Call  
24-Months  
(+/- 60 Days) 
 
 
 
 
Office 
Visit 
36-Months  
(+/- 60 Days) 
 
 
 
 
Office 
Visit 
Informed Consent 
X 
 
 
 
 
 
 
 
 
 
General Entry Criteria 
X 
 
 
 
 
 
 
 
 
 
Angiographic Entry 
Criteria 
 
 
X 
 
 
 
 
 
 
 
Demographics and Medical 
History  
X 
 
 
 
 
 
 
 
 
 
Weight (Kg)/ Height (cm) 
X 
 
 
 
 
 
 
 
 
 
Vital Signs 
X 
 
X 
X 
 
X 
X 
 
X 
X 
BP Assessment1 
X1 
X1 
X 
X 
 
X 
X 
 
X 
X 
Laboratory Assessments2 
X2 
 
X2 
X2 
 
X2 
 
 
 
 
Test for Proteinuria3 
X3 
 
 
 
 
 
 
 
 
 
Physical Exam 
X 
 
X 
X 
 
X 
X 
 
X 
X 
Pregnancy Test4 
X4 
 
X4 
 
 
 
 
 
 
 
iCAST™ RX Stent System 
Placement 
 
 
X 
 
 
 
 
 
 
 
Duplex  Ultrasound 
 
 
 
X 
 
X 
 
 
 
 
Angiography5 
 
 
X5 
 
 
X5 
 
 
 
 
Concomitant Medications 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Adverse Events6 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
1A minimum of two office visits are required within the 14-day Medical Documentation Screening period. If the procedure is scheduled > 14 days from the first office visit, subjects should return every two weeks 
(+/- 3 days) for BP assessments and monitoring. 
2Chem12 panel which includes: Glucose, Calcium, Albumin, Total protein, Sodium, Potassium, CO2, Chloride, BUN, creatinine, ALP, ALT, AST, and bilirubin. 
3 Test for proteinuria should be completed for subjects during Step 2 of the Medical Documentation Screening Period. 
4Pregnancy test required at screening and on the day of procedure for females of childbearing potential only. 
5 All subjects must have angiography to determine percent diameter stenosis prior to treatment and at 9-months (if DUS indicates ≥ 60% stenosis). 
6 AE collection (serious and non-serious) will begin upon completion of the ICF process through the 9-month follow-up visit, thereafter only SAEs and UADEs will be recorded. 
7 Subjects with a history of > 1 month stable medication per protocol and documented SBP ≥ 155mmHg will be allowed to skip the formal Screening period. All other protocol requirements that would have 
normally occurred during the two week screening period must still be completed prior to day of procedure.

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APPENDIX 5: REFERENCES 
1. Carr TM, Sabri SS, Turba UC, et al .Stenting for atherosclerotic renal artery stenosis. Tech Vasc Interv Radiol. 
2010 Jun;13(2):134-45.  
2. Rocha-Singh K, Jaff MR, Lynne Kelley E. Renal artery stenting with noninvasive duplex ultrasound follow-
up: 3-year results from the RENAISSANCE renal stent trial. Catheter Cardiovasc Interv 2008;72:853–862. 
3. Van Jaarsveld BC, Krijnen P, PietermanH, Derkx FH, Deinum J, et al. the effect of balloon angioplasty on 
hypertension in atherosclerotic renal artery stenosis, Dutch Renal Artery Stenosis Intervention Cooperative 
Trial Group, N Engl J Med 2000; 342:1007-1014 
4. Hoffman O, Carreres T, Sapoval MR, Auguste MC, Beyssen BM, Raynaud AC, Gaux JC. Ostial renal artery 
stenosis angioplasty: Immediate and mid-term angiographic and clinical results. J Vasc Interv Radiol 
1998;9(Part 1):65-73. 
5. Hirsch A, Haskal Z, Hertzer N, et al. ACC/AHA 2005 practice guidelines for the management of patients with 
peripheral arterial disease (lower extremity, renal mesenteric and abdominal aortic): a collaborative report 
from the American Association for Vascular Surgery/Society for Vascular Surgery, Society for Cardiovascular 
Angiography and Intervention, Society for Vascular Medicine and Biology, Society of Interventional 
Radiology, and the ACC/AHA Task Force on Practice Guidelines (Writing Committee to Develop Guidelines 
for the Management of Patients with Peripheral Arterial Disease). Circulation 2006; 113:e463-e654.  
6. Weibull H, Bergqvist D, Jonsson K, Hulthen L, Mannheim P, Bergentz SE. long term results after 
percutaneous transluminal angioplasty of the atherosclerotic renal artery stenosis – the importance of intensive 
follow-up. Eur J Vasc Surg 1991;5:291-301. 
7. Symonides B, Januszewicz A, Rowinski O, Januszewicz M, Chodakowska J, Berent H, Kuczynska K, 
Szmigielski C, Malek G, Januszewicz W. plasma fibrinogen as a risk factor for restenosis after percutaneous 
transluminal renal angioplasty in patients with atherosclerotic renal artery stenosis. J Cardiovasc Risk 
1999;6:269-272. 
8. Van de Ven PJ, Kaatee R, Beutler JJ, Beek FJ, Woittiez AJ, Buskens E, Koomans HA, Mali WP. Arterial 
stenting and balloon angioplasty in ostial atherosclerotic renovascular disease: A randomized trial. Lancet 
1999;353:282-286. 
9. Rocha-Singh K, Jaff M, Rosenfield K, et al. Evaluation of the safety and effectiveness of renal artery stenting 
after unsuccessful balloon angioplasty: The results of the ASPIRE-2 study. J Am Coll Cardiol 2005; 46:776-
783.  
10. Cooper C, Murphy T, Matsumoto A, et al. Stent revascularization for the prevention of cardiovascular and 
renal events among patients with renal artery stenosis and systolic hypertension: rationale and design of the 
CORAL trial. Am Heart J 2006; 152:59-66. 
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angioplasty versus surgical reconstruction of atherosclerotic renal artery stenosis: A prospective randomized 
trial. J Vasc Surg 1993;18:841-850;discussion 850-852. 
12. Plouin PF, Chatellier G, Darne B, et al. Blood pressure outcome of angioplasty in artherosclerotic renal artery 
stenosis : A randomised trial. The EMMA-Trial Group. Hypertension 1998;31:823-829. 
13. Webster J, Marshall F, Abdalla M, et al. Randomised comparison of percutaneous angioplasty vs continued 
medical therapy for hypertensive patients with atheromatous renal artery stenosis. J Hum Hypertens 
1998;12:329-335. 
14.  The ASTRAL Investigators. Revascularization versus Medical Therapy for renal artery stenosis. The 
ASTRAL investigators. N Engl J Med 2009;361:1953-62. 
15. Sharafuddin M, Raboi C, Abu-Yousef M, et al. renal artery stenosis: Duplex US after angioplasty and stent 
placement. Radiology 2001;220:168-173. 
16. Lederman RJ, Mendelsohn FO, Santos R, et al. Primary renal artery stenting: characteristics and outcomes 
after 363 procedures. Am Heart J. 2001;142:314–323. 

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17. Corriere MA, Pearce JD, Edwards MS, et al. Endovascular management of atherosclerotic renovascular 
disease: Early results following primary intervention. J Vasc Surg 2008;48:580–587. 
18. Stone GW, Goldberg S, Mehran R, et al. A prospective, randomized U.S. trial of the PTFE-covered Jostent for 
the treatment of diseased saphenous vein grafts: The BARRICADE trial (Abstr). J Am Coll Cardiol 
2005;45:27A. 
19. Bates MC, Shamsham FM, Faulknier B, et al. Artery perforation during catheterization: Fighting with a 
catastrophe. Catheter Cardiovasc Interv 2002;57:44–46. 
20. Allaire E, Melliere D, Poussier B, et al. Iliac artery rupture during balloon dilatation: What treatment? Ann 
Vasc Surgery 2003;17:306–314. Epub 2003 Apr 28. 
21. Beek FJ, Kaatee R, Beutler JJ, et al. Complications during renal artery stent placement for atherosclerotic 
ostial stenosis. Cardiovasc Interv Radiol 1997;20:184–190. 
22. Kohler Tr, Zierler RE, Martin RL, Nicholls SC, Gergelin RO, Kazmers A, Beach KW, Strandness DE Jr. 
Noninvasive diagnosis of renal artery stenosis by ultrasonic duplex scanning. J Vasc Surg 1986;4:450-456. 
23. Patel PM, Eisenberg J, Islam MA,  et al. Percutaneous revascularization of persistent renal artery in-stent 
restenosis. Vasc Med 2009; 14: 259. 
24. Anchala PR. Resnick SA. The current state of endovascular therapy in the evaluation and management of 
renovascular disease. Semin Intervent Radiol. 2009 Dec;26(4):333-44. 
25. Lakshminarayan Y,  De A, Jolly N. Covered Stents in Renal Artery Interventions. Cath Lab Digest Archive 
October, 2010. 
26. Leertouwer TC, Gussenhoven EJ, Bosch JL et al.  Stent Placement for Renal Arterial Stenosis: Where Do We 
Stand? A Meta-analysis. Radiology 2000; 216:78–85. 
27. Miller R. HERCULES: Renal Stenting lowers BP, but BNP is not a marker of benefit. Interventional Surgery. 
2011.  
28. Taylor DC, Kettler MD, Monetta GL, Kohler TR, Kazmers A, Beach KW, Strandness De Jr. Duplex 
ultrasound scanning in the diagnosis of renal artery stenosis: A prospective evaluation. J Vasc Surg 
1988;7:363-369. 
29. Olin JW, Piedmonte MR, Young JR, DeAnna S, Grubb M, Childs MB. The utility of duplex ultrasound 
scanning of the renal arteries for diagnosing significant renal artery stenosis. Ann Intern Med 1995;122:833-
838. 
30. Zierler RE. Is duplex scanning the best screening test for renal artery stenosis? Semin Vasc Surg 2001;14:177-
185. 
31. Carman TL, Olin JW, Czum J. Noninvasive imaging of the renal arteries. Urol Clin North Am 2001;28:815-
826. 
32. Bakker J, Beutler J, Elgersma O, et al. Duplex ultrasonography in assessing restenosis of renal artery stents. 
Cardiovasc Intervent Radiol 1999;22:475-480. 
33. The Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. 
The seventh report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of 
High Blood Pressure. 2004. 
34. Rabbia, C, Pini R. Evidence-based medicine in renal artery stenting. Journal of Cardiovascular Surgery 2010; 
51: 755-63. 
35. Balachandran KP, Oldroyd KG. Successful reintroduction of previously failed ACE inhibitor therapy 
following stenting of atherosclerotic renovascular disease. Indian Heart J. 2008 Jan-Feb;60(1):55-7. 
36. Rocha-Singh KJ, Novack V, Pencina M et al. Objective performance goals of safety and blood pressure 
efficacy for clinical trials of renal artery bare metal stents in hypertensive patients with atherosclerotic renal 
artery stenosis. Catheter Cardiovasc Interv. 2011. 
37. Rundback JH, Sacks D, Kent KC, et al. Guidelines for the reporting of renal artery revascularization in clinical 
trials. American Heart Association. Circulation. 2002;106:1572–1585. 

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38. Kandarpa K J, Becker GJ, Hunink MGM, et al. Transcatheter Interventions for the Treatment of Peripheral 
Atherosclerotic Lesions. Vasc Interv Radiology 2001 (12)6: 683-695. 
39. Laird JR, Rundback J, Zierler E, et al. Safety and Efficacy of Renal Artery Stenting Following Suboptimal 
Renal Angioplasty for De Novo and Restenotic Ostial Lesions: Results from a Nonrandomized, Prospective 
Multicenter Registry. J Vasc Interv Radiol 2010; 21:627–637. 
40. Fleming Sh, Davis RP, Craven TE et al. Accuracy of duplex sonography scans after artery stenting. J Vasc 
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41. Corriere MA, Edwards MS, Pearce JD, et al. Restenosis after renal artery angioplasty and stenting: Incidence 
and risk factors J Vasc Surg. 2009 October; 50(4): 813–819.  
42. Nolan BW, Schermerhorn ML, Powell RJ, et al. Restenosis in gold-coated renal artery stents.  J Vasc Surg 
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43. Nolan BW, Schermerhorn ML, Rowell E, et al. Outcomes of renal artery angioplasty and stenting using low-
profile systems.  J Vasc Surg 2005;41:46-52. 
44. Sapoval M, Zähringer M, Pattynama P, Rabbia C, et al. Low-profile stent system for treatment of 
atherosclerotic renal artery stenosis: the GREAT trial. J Vasc Interv Radiol. 2005 Sep; 16(9):1195-202. 
45. Shammas NW, Kapalis MJ, Dippel EJ, et al. Clinical and angiographic predictors of restenosis following renal 
artery stenting. J Invasive Cardiol. 2004;16:10–13. 
46. Rundback JH, Gray RJ, Rozenblit G, et al. Renal artery stent placement for the management of ischemic 
nephropathy. J Vasc Interv Radiol 1998; 9:413–420. 
47. Tullis MJ, Zierler RE, Glickerman DJ, Bergelin RO, Cantwell-Gab K, Strandness DE Jr. Results of 
percutaneous transluminal angioplasty for atherosclerotic renal artery stenosis: a follow-up study with duplex 
ultrasonography. J Vasc Surg 1997; 25:46–54. 
48. Harden PN, MacLeod MJ, Rodger RSC, et al. Effect of renal artery stenting on progression of renovascular 
renal failure. Lancet 1997; 349:1133–1136. 
49. White CJ, Ramee SR, Collins TJ, Jenkins JS, Escobar A, Shaw D. Renal artery stent placement: utility in 
lesions difficult to treat with balloon angioplasty. J Am Coll Cardiol 1997; 30:1445–1450. 
50. Iannone LA, Underwood PL, Nath A, Tannenbaum MA, Ghali MGH, Clevenger LD. Effect of primary 
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51. Dorros G, Jaff M, Mathiak L, et al. Four year follow-up of Palmaz-Schatz stent revascularization as treatment 
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52. Hennequin LM, Joffre FG, Rousseau HP, et al. Renal artery stent placement: long-term results with the 
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53. Pickering TG, Hall JE, Appel LJ, et al. Recommendations for Blood Pressure Measurement in Humans and 
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