JetStream Atherectomy for the Treatment of In-stent Restenosis of the Femoropopliteal Artery
Phase: NA
Conditions: Femoropopliteal In-stent Restenosis
Sponsor: Midwest Cardiovascular Research Foundation

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 1 of 68 
  
 
Study Protocol MCRF-S-002-2015 
 
JET-ISR Trial 
 
JetStream Atherectomy for the Treatment of In-stent 
Restenosis of the Femoropopliteal Artery 
Version 2 
29 FEB 2016 
 
Sponsor 
Midwest Cardiovascular Research Foundation 
 
National Principal Investigators 
Nicolas W Shammas, MD, MS, FACC, FSCAI 
Subhash Banerjee, MD, FACC, FSCAI 
 
Supported by 
Boston Scientific 
 
 
CONFIDENTIAL INFORMATION 
No use or disclosure of information contained within this document is permitted 
without prior written authorization from the Midwest Cardiovascular Research 
Foundation 
 
 

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 2 of 68 
Study Protocol Acceptance 
I have read this Study Protocol and agree to adhere to the requirements.  I will provide 
copies of this Study Protocol and all pertinent information to the study personnel.  I will 
discuss this material with them and ensure they are fully informed regarding the study 
devices and the conduct of the study according to the International Conference on 
Harmonization of Good Clinical Practices (ICH GCP) Guidelines, the Declaration of 
Helsinki, and the pertinent individual country laws/regulations. 
 
 
 
 
 
_______________________________ 
 
 
_____/______/_______ 
Principal Investigator Signature 
 
 
 
  DD MMM   YYYY 
 
 
________________________________ 
Principal Investigator Printed Name 
 
________________________________ 
Study Site 
 
 
 
 
 
 
 
 
 
 
 
 

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Study Protocol Synopsis 
 
JET-ISR trial 
Protocol Number MCRF-S002-2015 
Devices JetStream Navitus XC 2.1 and 2.4 
Primary Purpose 
The purpose of this study is to test the hypothesis that Jetstream atherectomy 
and adjunctive balloon angioplasty (JS +PTA) improves target lesion 
revascularization (TLR) at 6 months follow-up when compared to historic 
data from balloon angioplasty alone (PTA) in the treatment of 
femoropopliteal arterial In-stent restenotic (ISR) disease 
Study Design 
A prospective, multicenter, single arm study evaluating the investigational 
use of Jetstream Atherectomy (JS) and adjunctive balloon angioplasty (JS 
+PTA)  in the treatment of femoropopliteal ISR lesions in subjects with 
claudication or limb ischemia (Rutherford clinical category (RCC) of 2-4) 
(lesion length ≥ 4 cm). The comparator arm is historic data from plain old 
balloon angioplasty derived from a Meta-analysis of the 3 published 
randomized trials in the field.   
Follow-Up 
Schedule 
Follow-up assessments will occur at pre-discharge, 30 days, 6 months and 
1 year following the study procedure.   
Statistical 
assumption and 
analysis 
Assumptions: 
 
TLR with bailout stenting from historic control from meta-analysis: 
 
37.9% 
TLR with bailout stenting from Jetstream ISR feasibility study: 
 
20.7% 
Power 80% 
Alpha 0.05 
 
We are planning a study of independent cases and controls with 1 
control(s) per case.  Prior data indicate that the failure rate among controls is 
0.38.  If the true failure rate for experimental subjects is 0.21, we will need to 
study 112 experimental subjects and 112 control subjects to be able to reject 
the null hypothesis that the failure rates for experimental and control subjects 
are equal with probability (power) 0.8 (meta-analysis from published 
randomized trials provides data on 182 controls).   The Type I error 
probability associated with this test of this null hypothesis is 0.05.  We will 
use an uncorrected chi-squared statistic to evaluate this null hypothesis. 
Assumingly a loss of 20% of patients on follow-up a minimum of 134 
patients will be enrolled.  
 
Number of Sites Up to 14 sites in the  USA 

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 4 of 68 
Primary  
Outcomes  
 
Effectiveness: Target Lesion Revascularization (TLR) at 6 months: TLR 
is defined as retreatment of the index lesion (extended 1 cm proximal and 
distal to the lesion) at 6 months. For the primary endpoint, intra-procedural 
bail out stenting of the index lesion is considered meeting a TLR endpoint. 
(ITT analysis) 
Safety: Major Adverse Events (MAE) at 30 days: unplanned amputation, 
total mortality or TLR at 30 days (TLR includes bail out stenting)  
DSMB The study will be evaluated for safety after the first 60 patients enrolled. 
Stopping rule will be based on freedom from MAE at 30 days that is > 78% 
(bailout stent in the PTA control arm ranged from 7 to 20% in the 
randomized trial. Bailout stent is included as a MAE (part of the TLR 
definition). If maximum bailout stent occurs (20%), this allows a 2 % 
amputation/death rate within 1 month before the study is stopped i.e. total 
events of 22%, or freedom from events of 78%).  
Secondary 
endpoints 
 
1. 
Device Outcome:  Categorized by < 50% residual stenosis following 
JS atherectomy alone and without additional adjunctive PTA or bail out 
procedures as determined by the Angiographic Core Laboratory. 
2. 
Procedural Outcome: Categorized by < 30% residual stenosis 
following the protocol-defined treatment (JS + PTA) with provisional 
or bail out procedures as determined by the Angiographic Core 
Laboratory. 
3. 
Procedural Success: Defined as ≤30% residual diameter stenosis 
following JS + PTA without provisional or bailout procedures. 
4. 
Target Lesion Revascularization (TLR) at 6 months (with no 
bailout stent included): TLR is defined as retreatment of the index 
lesion (extended 1 cm proximal and distal to the lesion) at 6 months. 
Intra-procedural bail out stenting of the index lesion is NOT considered 
meeting a TLR endpoint. (ITT analysis) 
5. 
Target Lesion Revascularization (TLR) at 1 year: TLR is defined as 
retreatment of the index lesion (extended 1 cm proximal and distal to 
the lesion) at 1 year 
                                ITT (bail out stent in the Lab is considered as TLR)  
                      ITT (bail out stent in the Lab is not considered as TLR) 
6. 
Target Lesion Patency at 6 months and 1 year: Defined as PSVR ≤ 
2.5 at the treated site or < 50% stenosis by angiography as determined 
by the Angiographic Core Laboratory  in the absence of TLR, 
amputation, and/or surgical bypass (the evaluation of patency is 
extended to one cm proximal and one cm distal to the target lesion) 
7. 
Clinically Driven Target Lesion Revascularization at 6 months and 
1 year: Defined as any re-intervention or artery bypass graft surgery 
involving the target lesion in which the subject has a ≥ 70% diameter 
stenosis (Peak Systolic Velocity Ratio (PSVR) > 3.5 or on 

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 5 of 68 
angiography) and at least two of the following:  worsening RCC by one 
category, worsening WIQ score by ≥20 points, or an ABI drop > 0.15 
from baseline. 
                      ITT (bail out stent in the Lab is considered as TLR)  
                      ITT (bail out stent in the Lab is not considered as TLR)  
Routine angiography in an asymptomatic patient at 6 months or 1 year is not 
required in this protocol.  
8. 
Target Vessel Failure at 6 months and 1 year: Defined as major 
unplanned amputation related to the treated limb, vascular mortality 
related to treated limb and target vessel revascularization at 6 months  
and 1 year (stenting in the lab is not considered a TLR/TVR) 
9. 
Target Lesion failure at 6 months and 1 year: Defined as major 
unplanned amputation related of the treated limb, vascular mortality 
related to treated limb and target lesion revascularization at 6 months 
and 1 year (stenting in the lab is not considered a TLR) 
10. Major Adverse Events (MAE) as individual endpoints in-hospital 
and up to 30 days :  Include device-induced vascular injury as 
reported by the operator, amputation (major and minor unplanned), 
death, significant distal embolization requiring the use of 
pharmacologic or mechanical means to treat (other than a vasodilator), 
perforation (extravasation of blood outside the vessel wall), major 
bleeding, non-fatal myocardial infarction (defined as the occurrence of 
more than 20 minutes of chest pain post procedure with an increase in 
troponin), stroke, access complications (AV fistula and 
pseudoaneurysm), bail out stenting, acute renal failure (drop in crcl by 
> 25% from baseline), acute (< 24 hours) or subacute (< 1 month , > 
than 24 hours) vessel closure. 
11. Major Adverse Event Rate at 6 months and 1 Year: Defined as 
major unplanned amputation of the treated limb, all-cause mortality or 
TLR at 6 months and 1 year (bail out stent in the Lab is included as 
TLR) 
12. Change in WIQ Score at 6 Months and 1 Year: Defined as the 
change in Walking Impairment Questionnaire (WIQ) score at 6 months 
and 1 year compared to baseline. 
13. Change in Rutherford Clinical Category at 6 Months and 1 Year:  
Defined as the change in clinical status indicated by the change in RCC 
at 6 months and 1 year compared to baseline, that is attributable to the 
treated limb (in cases of bilateral disease).  
14. Change in Ankle-Brachial Index at 6 Months and 1 Year:  Defined 
as the change in the ankle-brachial index (ABI) at 6 months and 1 year 
compared to baseline in subjects with compressible arteries and 
baseline ABI < 0.9.  

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 6 of 68 
15. Assisted Primary Patency rate at 1 year: Defined as < 50% stenosis 
per angiography as determined by the Angiographic Core Laboratory, 
or PSVR ≤ 2.5 at 1 year,  maintained by repeat percutaneous 
intervention of a restenotic but not occluded index lesion  
16. Secondary Patency rate at 1 year: Defined as < 50% stenosis per 
angiography as determined by the Angiographic Core Laboratory, or 
PSVR ≤ 2.5 at 1 year, maintained by repeat percutaneous intervention 
of a  restenotic or occluded vessel 
 
 
 
 

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 7 of 68 
ABBREVIATIONS 
 
ABI 
 
Ankle Brachial Index 
ACT  
Activated Coagulation Time 
AE 
 
Adverse Event 
ASA  
Acetylsalicylic Acid (aspirin) 
AT 
 
Anterior Tibial 
atm 
 
atmospheres (mm/Hg) 
AV 
 
Arteriovenous 
CABG  
Coronary Artery Bypass Graft 
CBC  
Complete Blood Count 
CFA  
Common Femoral Artery 
CFR 
 
Code of Federal Regulations 
CSA  
Cross-Sectional Area 
CTO  
Chronic Total Occlusion 
CVA  
Cerebrovascular Accident 
DES 
 
Drug Eluting Stent 
ECG  
Electrocardiography 
eCRF  
Electronic Case Report Form 
EOB  
Explanation of Benefits 
FDA  
United States Food and Drug Administration 
GCP  
Good Clinical Practices 
GpIIb/IIIa 
Glycoprotein IIb/IIIa 
ICF 
 
Informed Consent Form 
ICH 
 
International Conference on Harmonization 
IFU 
 
Instructions for Use 
IRB 
 
Institutional Review Board 
IVUS  
Intravascular Ultrasound 
MAE  
Major Adverse Events 
MI 
 
Myocardial Infarction 
PAD  
Peripheral Arterial Disease 
PTA 
 
Plain Old Balloon Angioplasty 
PSV 
 
Peak Systolic Velocity 
PSVR  
Peak Systolic Velocity Ratio 
PT 
 
Posterior Tibial 
QVA  
Quantitative Vascular Analysis 
SAE 
 
Serious Adverse Event 
SFA 
 
Superficial Femoral Artery 
TIA 
 
Transient Ischemic Attack 
TLR 
 
Target Lesion Revascularization 
TPT 
 
Tibial Peroneal Trunk 
TVR  
Target Vessel Revascularization 
UADE  
Unanticipated Adverse Device Effect 
US  
 
United States  
VF/VT 
Ventricular Fibrillation/Ventricular Tachycardia 
JS 
 
JetStream Navitus 

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 8 of 68 
 
TABLE OF CONTENTS 
1.0 
INTRODUCTION....................................................................................................... 9 
2.0 
DEVICE DESCRIPTIONS ...................................................................................... 10 
3.0 
BACKGROUND AND SIGNIFICANCE ............................................................... 11 
4.0 
METHODOLOGY ................................................................................................... 24 
5.0 
STATISTICAL METHODS .................................................................................... 42 
6.0 
RISK/BENEFIT ANALYSIS ................................................................................... 44 
7.0 
SITE REQUIREMENTS ......................................................................................... 46 
8.0 
MONITORING PROCEDURES ............................................................................ 47 
9.0 
RESPONSIBILITIES, RECORDS and REPORTS .............................................. 48 
10.0 
DATA and QUALITY MANAGEMENT ............................................................... 51 
11.0 
PUBLICATION STRATEGY ................................................................................. 52 
12.0 
DEFINITIONS .......................................................................................................... 53 
REFERENCES ...................................................................................................................... 62 
 
 
 
List of Tables 
 
 
 
Table 1: Study Assessment Requirements .............................................................................. 30 
Table 2: Baseline Requirements ............................................................................................. 31 
Table 3: Pre-Discharge Assessment Requirements ................................................................ 35 
Table 4: 30-Day Follow-Up Visit Requirements .................................................................... 37 
Table 5: 6-Month Follow-Up Visit Requirements .................................................................. 37 
Table 6: 1-Year Follow-up Visit Requirements...................................................................... 37 
Table 7: Principal Investigator Reporting Responsibilities .................................................... 50 
 
 

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 9 of 68 
1.0 INTRODUCTION 
PURPOSE 
The purpose of this single arm, prospective multicenter study is to test the hypothesis that 
JetStream atherectomy (JS) with adjunctive balloon angioplasty (PTA) in treating 
femoropopliteal in-stent restenosis (FP ISR) is superior to PTA alone using core lab, 
adjudicated historic control, in reducing the primary outcome of target lesion 
revascularization (TLR) at 6 months follow-up. 
DEVICE NAMES 
The JetStream XC rotational and aspiration atherectomy device (JS device). 
INTENDED USE 
The JS device catheter is intended for use in peripheral arterial intervention to treat 
denovo and non-stent restenotic infrainguinal lesions.  JS is not intended for use in the 
coronary, carotid, iliac or renal vasculature.   
JS application in treating FP ISR is off label and considered investigational 
DURATION OF THE STUDY 
The estimated duration of the study is approximately two years from the time of first 
subject enrollment to the last Study Protocol required follow-up visit.  Subjects will be 
followed for 6 months for the primary endpoint and 1 year for the secondary endpoints.   
NUMBER OF SITES AND SUBJECTS 
One hundred and 40 patients (140) subjects are planned for enrollment into this 
prospective registry at up to 14 study sites in the United States.   
PARTICIPATING INVESTIGATORS 
The study National Principal Investigators are Dr. Nicolas W. Shammas, MD, MS, 
FACC, FSCAI and Dr Subhash Banerjee, MD, FACC, FSCAI 
SPONSOR CONTACT INFORMATION 
 
Sponsor: Midwest Cardiovascular Research Foundation 
 
 
 
 
 
 
1622 E Lombard Street 
 
 
 
 
 
  
 
Davenport, IA 52803 
  
 
Phone: +1 563 3242828 
  
 
Fax: +1 563 3230217 
 Contact:   Gail Shammas, BSN, RN 
  
 
Clinical Research Manager 
  
 
Phone:  +1 563 3200264 
  
 
Email:  shammasg@mcrfmd.com 
 

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 10 of 68 
2.0 DEVICE DESCRIPTIONS 
JETSTREAM XC ATHERECTOMY DEVICE 
 
The Boston Scientific Jetstream XC catheter is a rotating, aspirating, expandable 
catheter for active removal of atherosclerotic disease and thrombus in peripheral 
vasculature. The JS XC System has been cleared by the FDA for use in the peripheral 
vasculature to treat denovo and non-stent infrainguinal lesions 
 
 
JETSTREAM XC™ device has 2 sets of blades: one set is at the tip of the catheter 
and the other (5 blades) is mounted proximal to the tip. Counterclockwise rotation 
expands the proximal blades and allows wider tissue cutting. The JetStream Navitus has 
been improved compared to its predecessor, the Pathway device, with the aspiration port 
placed proximal to the blades instead of distally, allowing a more robust aspiration 
capacity. The recommended use of this device with tips and tricks on how to operate it 
can be found in prior publications.1,2 
 
 
There are 2 cutter designs with the JETSTREAM device. The JETSTREAM® XC 
(or eXpandable Cutter Catheters) and the JETSTREAM® SC (or Single Cutter 
Catheters). The Expandable Cutter, as the name implies, can be used blades down (BD) 
and blades up (BU) with single insertion and are for femoropopliteal vessels. The XC or 
Expandable Cutters Catheters come in 2 sizes: 2.1mm/3.0mm (135 cm length) is best 
suited for vessel size larger than 3.0 BD and 4.0-5.0 mm BU; and the 2.4mm/3.4mm (120 
cm length) is typically used for vessels 4.0-4.9mm BD and 5.0 mm or larger BU. Also, 
the SC or Single Cutter Catheters come in two sizes: 1.6 mm (145 cm length) best suited 
for vessel size 2.0-2.5 mm; and the 1.85 mm (145 cm shaft length) typically used for 
vessel sizes 2.6-3.0 mm. The single cutters have only have a front end cutter with no BU 
feature and typically are used for proximal and mid tibial and peroneal vessels. The 
device is retracted through the treatment area by “rexing” it until wire loop is back to its 
initial size.  
 
 
 
http://www.bostonscientific.com/content/dam/bostonscientific/pi/portfolio-
group/Catheters%20Atherectomy/JetStream/Resources/4137-

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 11 of 68 
001%20JETSTREAM%20Brochure.pdf/ 
 
3.0 BACKGROUND AND SIGNIFICANCE 
3.1 DISEASE OVERVIEW 
In 2001, in the United States alone, the prevalence of peripheral arterial disease 
(PAD) is estimated to be 8-12 million people.  Endovascular therapy has exponentially 
increased over the past decade and is now applied in the majority of patients undergoing 
PAD treatment with revascularization. The tool box to treat infrainguinal PAD has 
expanded significantly and includes plain old balloon angioplasty (PTA), atherectomy, 
stenting, specialized balloons, drug coated balloons (DCB) and Drug coated stents 
(DCS). In univariate analysis, PAD is more prevalent with age, men and Black 
population and less prevalent in Hispanic and Asians. Multivariate analysis continues to 
indicate that older age and Blacks are at a higher risk of PAD than the younger 
population or non-Hispanic Whites respectively even when adjusting for traditional risk 
factors such as diabetes, hypertension, hyperlipidemia, smoking and history of coronary 
artery disease (2b). 
Several studies have shown that stenting of the femoropopliteal artery (FP) leads to 
higher long term patency. Bare metal stents have not shown conclusively to reduce target 
lesion revascularization (TLR) which is in contrast to DCB and DCS3,4,5,6.  Irrespective, 
stenting has several disadvantages including a continued high rate of restenosis and stent 
fractures that is progressive with time7,8. FP ISR occurs in more than one third of patients 
at 1 year and up to 49% at 2 years3-8. Complex lesions (long, Trans-Atlantic Inter-Society 
Consensus II C/D lesions, total occlusions), certain demographics (female gender, 
diabetes mellitus), critical limb ischemia and significant stent fractures are associated 
with a higher rate of restenosis9.  Also the majority of occluded stents are restenotic-
thrombotic and generally are more challenging to treat.  
3.2     Therapies in Treating FP ISR  
Several methods have been proposed to treat FP-ISR including plain old balloon 
angioplasty (PTA), cryoplasty (PolarCath, Boston Scientific, Natick, Mass) , cutting 
balloons, drug-eluting self-expanding stents (Zilver X) (Cook Medical, Bloomington, IN, 
USA), rotational and aspiration atherectomy including the Rotarex S (Staub Medical AG, 
Wangs, Switzerland) and JetStream (Boston Scientific, Maple Grove, MN), directional 
atherectomy with SilverHawk (MDT, USA)), laser ablation (Excimer laser, 
Spectranetics, Colorado Springs, Co, USA), Viabahn covered stents (W.L.Gore and 
Associates, Newark, DE) and DCB10-20.   
Early observational data attempted debulking of FP ISR to reduce restenotic tissue 
burden and theoretically delay or reduce the rate of repeat revascularization.  Silingardi et 
al21 reported their experience with the Rotarex S device in treating 32 patients with 
subacute or chronic FP (n=26) or iliac (n=6) ISR. Although technical success was 100%, 
primary patency at 6 months and 12 months was 75% and 58.1% respectively. On the 
other hand, Wissgott et al.22 reported on 78 patients with ISR treated with the Rotarex S 
catheter (lesion length 147 mm). Technical success was high at 97.4% and restenosis at 1 

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 12 of 68 
year was remarkably low at 18.4%. SilverHawk atherectomy also showed mixed results. 
In a cohort of 43 patients with FP ISR (mean lesion length of 131 mm), Zeller et al12 
showed patency and TLR rates of 54% and 53% respectively at one year with the 
SilverHawk catheter (currently contraindicated in treating FP ISR). Given the 
approximate same mean lesion length (mean of 126.2 mm), Shammas et al10, showed a 
TLR rate of 31.7% in 41 consecutive patients treated for FP ISR at one year with 
SilverHawk. Laird et al.23recently reported the results of the SALVAGE trial with the use 
of the excimer laser and the Viabahn (W.L.Gore and Associates, Newark, DE) covered 
stent in treating FP ISR. The primary patency at 12 months was measured by duplex 
ultrasonography. Twenty-seven patients were enrolled. The mean lesion length was 200.7 
mm and the majority of lesions were TASC C/D. Procedural success was achieved in 
100% of cases. Primary patency and TLR at 12 months were 48% and 17.4% 
respectively. This prospective single arm registry does not distinguish, however, between 
the relative effectiveness of the laser versus the Viabahn endograft stent in reducing 
restenosis in FP ISR lesions.  
Recently 3 randomized trials were presented in treating FP ISR; the EXCITE ISR 
trial (randomized laser + PTA vs PTA alone),  the RELINE trial (randomized Viabahn 
stent vs PTA) and the Randomized Femoral Artery In-Stent Restenosis (FAIR) 
Trial.18,19,34. In the GORE VIABAHN (W.L Gore and Associates, Newark, Delaware, 
USA) Versus Plain Old Balloon Angioplasty (PTA) for Superficial Femoral Artery 
(SFA) In-Stent Restenosis (RELINE) trial19, Viabhan endograft stent was shown to be 
superior to PTA leading to significantly better patency rates at 1 year (37% versus 74.8% 
respectively). In the EXCImer Laser Randomized Controlled Study for Treatment of 
FemoropopliTEal In-Stent Restenosis (EXCITE ISR) trial18, a multicenter, prospective, 
randomized, controlled trial conducted across 40 U.S. centers. A total of 169 ELA + PTA 
subjects (62.7% male; mean age 68.5 ± 9.8 years) and 81 PTA patients (61.7% male; 
mean age 67.8 ± 10.3 years) were enrolled. Mean lesion length was 19.6 ± 12.0 cm 
versus 19.3 ± 11.9 cm, and 30.5% versus 36.8% of patients exhibited total occlusion. 
ELA + PTA subjects demonstrated superior procedural success (93.5% vs. 82.7%; p = 
0.01) with significantly fewer procedural complications. ELA + PTA and PTA subject 6-
month freedom from TLR was 73.5% versus 51.8% (p < 0.005), and 30-day major 
adverse event rates were 5.8% versus 20.5% (p < 0.001), respectively. ELA + PTA was 
associated with a 52% reduction in TLR (hazard ratio: 0.48; 95% confidence interval: 
0.31 to 0.74). This trial showed that debulking with the laser is an important strategy to 
reduce TLR in treating FP ISR when compared to PTA. Finally, The Randomized 
Femoral Artery In-Stent Restenosis (FAIR) Trial34, randomized 119 patients with 
superficial femoral artery in-stent restenosis to drug coated balloon (DCB) (n=62) versus 
PTA (n=57). Mean lesion length was 82.2±68.4 mm. and 28.6% of lesions were totally 
occluded. The primary end point of recurrent in-stent restenosis assessed by ultrasound at 
6 months was 15.4% (8 of 52) in the DCB and 44.7% (21 of 47) in the PTA group 
(P=0.002). Freedom from target lesion revascularization was 96.4% versus 81.0% 
(P=0.0117) at 6 months and 90.8% versus 52.6% (P<0.0001) at 12 months, respectively. 
No major amputation was needed. Two patients in the DCB and 3 patients in the PTA 
group died. No death was procedure related. 

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 13 of 68 
Drug coated balloons (DCB)16,17,24 and drug coated stents (DCS)15 have emerged as 
promising technology in the treatment of FP ISR. Data however is mostly applicable for 
short (less than 10 cm) and intermediate lesions (10-15 cm). Patency with DCB ranged 
from 70.5 to 92.1% with TLR from 9.2 to 13.6% at 1 year. Also in intermediate lesions, 
DCS using the Zilver PTX showed patency and TLR rates of 95% and 3.8% and 78.8% 
and 19% at 6 months and 1 year follow up respectively. Combining atherectomy and 
DCB may offer a superior treatment modality than either device alone.  A small 
observational study showed that laser with DCB has a patency of 91.7% and TLR of 
7.1% at a mean follow up of 19.1 months.  Also DCB with directional atherectomy 
yielded a patency rate of 84.7% at 1 year in mean lesion length of 15.3 cm25,26. Studies 
are currently ongoing to test this hypothesis.  
Below is a bar graph summarizing data from trials of FP ISR treatment.  
 
 
 
 
3.3      JetStream Atherectomy in Treating FP ISR 
3.31 Preclinial Studies 
Preclinical data was recently presented at CRT 2015 on the application of JetStream 
atherectomy in ISR and published in JEVT29. Below is a description of these preGLP 
experiments.  
Preprocedure Animal Care 

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 14 of 68 
A Yorkshire swine model was chosen as the experimental animal because of the 
similarity to humans in terms of the size and anatomy of the cardiovascular system. 
Furthermore, this model has been validated for the occurrence of restenosis within 1 
month of stent/balloon overstretch injury, making it more practical for testing medical 
devices in treating ISR. All animals were held in quarantine and housed at CBSET 
(Lexington, MA, USA), a facility accredited by the American Association for 
Accreditation of Laboratory Animal Care, under conditions that met or exceeded 
requirements as set forth in the USDA guidelines.1,2 Standard veterinary practices were 
performed during quarantine, including physical examinations and clinical pathology to 
determine health status before assignment to the study. A nutritionally balanced diet 
appropriate for the species was offered daily to all animals with water ad lib. Animals 
were released from quarantine by the veterinary staff when deemed healthy.  
Animal Preparation  
 
All animals were pretreated 1 day before stent implantation with aspirin 650 
orally and clopidogrel 300 mg orally. They were maintained on aspirin (81 mg daily 
orally) and clopidogrel (75 mg daily orally) thereafter until euthanized. Animals received 
Telazol (4–6 mg/kg) intramuscularly as a pre-anesthetic. Isoflurane anesthesia was then 
administered to effect via mask/nosecone, and endotracheal intubation was then 
performed. Following intubation, the animals were maintained on continuous inhalant 
isoflurane anesthesia delivered for the remainder of the procedure. Perioperative 
nifedipine (10 mg/animal placed sublingually) was also administered. The animals were 
prepared for surgery using accepted veterinary care standards. Electrocardiogram leads, a 
pulse oximetry sensor, and a temperature probe were placed for continuous monitoring of 
vital signs. Pre-emptive analgesia (buprenorphine; 0.01–0.03 mg/kg), was administered 
intramuscularly at anesthesia (prior to surgical incision). The incision site was prepared 
and appropriately draped for aseptic procedures. 
Stent Implantation Procedure 
 
The right carotid artery was accessed using a cutdown approach. An introducer 
sheath was advanced into the artery and heparin (50–200 U/kg) was administered 
intravenously to prolong the activated coagulation time to a target of >275 seconds. A 
guide catheter was then advanced to the iliac arteries under fluoroscopic guidance. The 
femoral arteries were crossed with a 0.035-inch J-tipped guidewire, and the target 
segment was dilated 3 times (30 seconds each) with an oversized angioplasty balloon at 
various pressures and to achieve a 1.2 to 1.5 balloon:artery ratio. Two overlapping 40-
mm-long nitinol S.M.A.R.T. self-expanding stents (5.0 and 6.0 mm in diameter; Cordis 
Corporation, Bridgewater, NJ, USA) were then deployed to the dilated target lesion 
(sized 1.2:1 stent:artery). The amount of overlap was either 100% (n=2) or 25% to 50% 
(n=6). The same process was repeated for the contralateral leg. A total of 8 stents were 
deployed in 4 limbs. Following stent implantation in both left and right femoral arteries, 
the animal is weaned off the anesthetic and extubated. Buprenorphine 0.01 to 0.03 mg/kg 
was administered intramuscularly every ~4 to 12 hours to provide analgesic coverage 
through at least the first 24 postoperative hours 
Atherectomy Procedure 

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 15 of 68 
 
Animals were brought back to the fluoroscopy suite approximately 1 month after 
stent implantation. The anesthesia procedure was repeated as described above. Carotid 
artery access was obtained using cutdown method. Angiographic images of the target 
vessel were obtained with contrast media to characterize the degree of ISR. Quantitative 
vessel angiography (QVA; Centricity Cardiology CA1000 Cardiac Review 2.0 software) 
was used to measure minimum lumen diameter (MLD), plaque surface area (PSA), and 
percent stenosis. An optimal residual stenosis after atherectomy alone was defined as a 
residual percent stenosis <50%.  
 
Atherectomy was then carried on by advancing the cutter at a slow speed of 1 to 2 
mm per seconds from the proximal to distal end of the stented segment (one run) over a 
Spartacore wire (Abbott Vascular, Redwood City, CA, USA). Two atherectomy runs 
with BD followed by QVA at the lesion site was performed. Atherectomy was then 
repeated with BU for 4 runs and with QVA of the lesion after each run (Figure 1).  
 
 
 
Intravascular ultrasound (IVUS) quantitative measurements were also performed 
at baseline, after 2 BD runs, and after each BU run (BU1, BU2, BU3, BU4) on a total of 
24 locations in the proximal, mid, and distal parts of the stented segments (Figure 2).  
 

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 16 of 68 
 
 
Minimum lumen area (MLA) within each the 24 locations was determined. PSA was 
calculated from the total stented area at each location minus the MLA. Finally, MLA and 
PSA at baseline were plotted against net MLA gain and PSA reduction (BU MLA or PSA 
– baseline MLA or PSA), respectively. The minimum MLA and PSA ranges at baseline 
needed for an increase in MLA by 1 to 2 mm and reduction in PSA by 5% to 10% from 
baseline were determined. 
 
Device interaction with the implanted stent and subsequent damage of the stent 
was carefully evaluated under fluoroscopy. The process was repeated for the contralateral 
limb. After the last treatment, the animal was euthanized. Stents were evaluated 
postmortem with high resolution radiographs to determine strut damage.  
Statistical analysis 
 
Descriptive analysis was performed on all angiographic variables. Single-sample 
Wilcoxon signed-rank test was performed between MLA obtained after BU runs and 
theoretical maximal MLA of the XC 2.4-3.4 cutter with BU model. Line graphs were 
performed to illustrate the change in MLD, MLA, PSA (with IVUS) and percent stenosis 
with each treatment. Wilcoxon signed-rank test and paired t test (1-tail) were performed 
to compare baseline, BD, and BU 1 to 4 runs using the statistical package in Minitab 17 
(State College, PA, USA). 
 
Results 
The mean vessel diameter was 4.7±0.6 mm and mean lesion length was 61.5±12.6 
mm. The mean baseline (n=8) MLD was 1.73±0.84 mm. Following 2BD and 1 BU runs, 
the mean MLDs were 2.6±0.7 mm (p=0.025) and 3.12±0.39 mm (p=0.005), respectively, 
vs baseline MLD. There was also a significant increase in MLD between 2BD runs and 

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 17 of 68 
BU1 run (p=0.005). No statistical difference in MLD was seen between BU runs (p>0.05; 
Figure 3A). 
 
PSA was significantly reduced between baseline (83.9%±14.8%) and 2 BD 
(67.7%±17.0%, p=0.005) and BU1 (55.4%±9.0%, p=0.005) runs and between BU1 and 
BU2 runs (50.7%±9.7%, p<0.05). No differences in PSA was seen between the BU2, 
BU3, and BU4 runs (p>0.05). Percent stenosis was reduced from a mean of 
63.13%±16.91% to 44.97%±15.0%8 (p=0.005) with BD runs and to 33.51%±6.73% 
(p=0.005) with BU1 run. There was also a significant reduction in percent stenosis 
between 2 BD runs and BU1 run (p=0.01) and between BU1 and BU2 runs 
(30.1%±7.0%, p=0.05). No difference between percent stenosis was seen between BU 2 
to 4 runs (p=0.10; Figure 3B). 
 
 
 
The mean baseline MLA by IVUS was 7.8±2.7 mm2. Following 2BD and 1 BU 
runs, the mean MLAs were 8.1±2.5 mm2 (p<0.044) and 8.7±2.0 mm2 (p=0.007), 
respectively, when compared to baseline MLA. There was also a significant increase in 
MLA between 2BD runs and BU1 run (p=0.033) and between BU1 and BU2 runs 
(9.4±2.4 mm2, p=0.007). No statistical difference in MLA was seen between BU 2 to 3 
runs (p>0.05; Figure 4A). 
 
PSA was significantly reduced between baseline (65.2%±11.7%) and 2 BD 
(63.0%±10.5%, p=0.015) and BU1 (60.7%±9.2%, p=0.011) runs and between BU1 and 
BU2 runs (57.5%±7.5%, p=0.025). No differences in PSA were seen between the BU2, 
BU3, and BU4 runs (p=0.12; Figure 4B) 
 
 

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Vessel area measured by IVUS at site of treated stenosis remained unchanged 
between baseline and BU4 run (23.3±5.8 vs 22.5±4.9 mm2, respectively; p=0.73). 
Furthermore, a significant correlation was seen between MLA at baseline and MLA after 
BU runs (p=0.006; Figure 5A) and between PSA at baseline and PSA after BU runs 
(p<0.0001; Figure 5B). An approximate baseline MLA of 8.0 to 9.0 mm2 led to an MLA 
gain of 1 to 2 mm2 and an approximate baseline PSA of 60% to 70% led to a reduction in 
PSA by 5% to 10% using the large cutter BU mode. Finally, theoretical MLA achievable 
from the XC BU 2.4-3.4 device is 9.08 mm2 (A = πr2 using r=3.4/2=1.7mm). No 
difference was seen between this calculated MLA and the IVUS measured MLAs after 
BU runs, indicating no orbital effect of the device on tissue cutting. 
 

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 19 of 68 
y = -0.4288x + 5.1567
-4
-3
-2
-1
0
1
2
3
4
5
0
2
4
6
8
10
12
14
16
Change in MLA after BU runs  from baseline 
(mm2)    
Baseline MLA (mm2)
y = -0.4843x + 23.725
-25
-20
-15
-10
-5
0
5
10
0
10
20
30
40
50
60
70
80
90
Change in PSA after BU runs (%)
Baseline PSA (%)
B
A
 
 
There were no observed angiographic stent disruptions or stent strut discontinuity 
with IVUS or high resolution radiography (Figure 6) with JetStream Navitus 
atherectomy.  
 
 
Using IVUS, JetStream Navitus is a true debulking device with no Dottering 
effect. In one study of post JetStream Navitus atherectomy, total vessel volume remained 
unchanged, but tissue volume is reduced and MLD is increased significantly.3 IVUS data 
confirm the same findings by showing that MLA is increased and PSA is reduced, 
indicating true tissue excision within a nitinol self-expanding stent. Furthermore, the 
median MLA change seen after BU runs was statistically similar to the theoretical MLA 
calculated using a BU large cutter, which indicates that effective cutting is limited to the 
perimeter of the device, with no “wobbling” or “orbital” effect. This is a limitation of the 

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 20 of 68 
device in treating femoropopliteal ISR, as suboptimal tissue excision is therefore 
expected in larger vessel diameter (possibly 7 mm or higher).  
 
In this model, stents were positioned at different overlapping lengths to test the 
safety of the device in treating short or long overlapping stent segments, particularly 
when the blades are up. No adverse events or stent-device interaction were seen. Also, 
there was no angiographic evidence of dissection or distal embolization following 
JetStream Navitus atherectomy, but it should be noted that these lesions are relatively 
short and not totally occluded; thus, they have a low potential for embolization.  
 
Finally, adjunctive balloon angioplasty was not performed after the JetStream 
Navitus as the intention of the study was to test the effectiveness and safety of the device 
itself rather than the final outcome after adjunctive balloon angioplasty. The residual 
narrowing post atherectomy was a mean of 30.1%, which is consistent with effective 
tissue debulking (<50% residual) with the JetStream Navitus alone and without balloon 
angioplasty. This residual narrowing was accomplished in a mean vessel diameter of 4.7 
mm.  
References: 
1. NRC (National Research Council). Guide for the Care and Use of Laboratory 
Animals. Washington, DC: The National Academies Press; 2011. 
2. American Veterinary Medical Association. AVMA Guidelines for the Euthanasia 
of Animals: 2013 Edition. Version 2013.0.1. Published March 2013. 
https://www.avma.org/KB/Policies/Documents/euthanasia.pdf. Accessed May 15, 2013. 
3. Singh T, Koul D, Szpunar S, et al. Tissue removal by ultrasound evaluation (the 
TRUE study): the Jetstream G2 system post-market peripheral vascular IVUS study. J 
Invasive Cardiol. 2011;23:269-273 
 
Data recently presented at ICI 2015 in Israel from the same above model using SEM 
and histopathology showed a variable tissue disruption of in-stent restenotic tissue with 
no evidence of adverse effects on the implanted artery (e.g., thrombosis, dissection) or 
the implanted stents. High resolution radiographs showed no evidence of strut fracture or 
displacement.  Histology and SEM showed, despite focal exposures of stent struts related 
to either incomplete neointimal coverage and/or atherectomy, there was no evidence of 
atherectomy-related damage to the stent in these areas. The degree of neointimal 
proliferation in this swine femoral artery ISR model was sufficient to evaluate the 
JetStream atherectomy catheter for safety. 
 

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3.32 Clinical studies 
Beschorner et al35 reported data on 33 patients (40 infrainguinal ISR lesions) treated 
with the Pathway PV atherectomy system (predecessor of JetStream). Primary patency 
was 33 % after 12 months and 25 % after 24 months. In this study, the majority of the 
lesions were FP (90%) but few lesions were in the peroneal, tibioperoneal and others. The 
vessels had no or mild (<30 degrees) tortuosity.  Lesion length was 85.7 mm. Total 
occlusions were present in 20% of vessels. No serious device-related events were noted. 
Acute procedural success was accomplished in all lesions with adjunctive balloon/stent 
treatment. Distal embolization occurred in 6% of lesions treated and required aspiration 
embolectomy successfully. Bail out stenting was need in one lesion (3%). The Pathway 
PV system used in this study required 8 F system. Since then, the device (currently the 
Jetstream XC) was improved upon with more powerful aspiration and cutting abilities 
and is now compatible with 7 F sheath.  
The recently presented final data of the JetStream ISR study at New Cardiovascular 
Horizon 201527 (one year TLR data will be presented at LINC 2016)  evaluated acute 
procedural and 6-month outcomes, and stent-device interaction of the JetStream Navitus 
in treating FP ISR from 2 U.S. centers (manuscript in Print in JEVT 2016. Copy of 
accepted manuscript is in Appendix B). Demographic, clinical, angiographic and 
procedural data were collected on 29 patients (32 limbs) included. The primary 
effectiveness endpoint was acute procedural success (<30% residual narrowing with no 
serious adverse events). The primary safety endpoint was freedom from major adverse 
events (MAE). Secondary endpoints include clinically driven target lesion 
revascularization (TLR) at 6 months and stent integrity as assessed by Angiographic Core 
Laboratory. Six-month follow-up was completed on 27 patients (29 limbs). Adjunctive 
balloon angioplasty was performed in 100% at a mean pressure of 11.6 ± 3.3 atm. Total 
lesion length was 17.4 ± 13.1 cm and total treated length 19.5 ± 12.9 cm. Acute 
procedural success occurred in 90.6% of limbs. Acute device success (<50% residual 
narrowing after atherectomy alone) was 75.9%. Embolic filter protection (EFP) was used 
in 16/32 (50.0%) of limbs. Macrodebris was noted in 2/16 (12.5%) of filters and distal 
embolization (DE) requiring treatment occurred in 3/32 limbs (9.4%) (2 with no EFP). 
There were no new stent fractures or deformities (n=24) post JS. On 6-month follow-up 
TLR occurred in 4/29 patients (13.8%). Patency rate (PSVR<2.4) was 72%.  Other non-

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 23 of 68 
procedure related adverse events were total death 3.4% and major bleeding 3.4%. These 
results were highly encouraging establishing in this feasibility small study the safety and 
effectiveness of the JetStream in treating FP ISR when compared to historic control.  
Observational data also are available from the multicenter xl-PAD registry that 
provided insight into how JetStream is applied in a real world registry28. Jetstream™ 
atherectomy was performed in 68 procedures. Patients’ average age was 68.5 years, 
66.2% were male, and 89.7% Caucasian. Average ankle-brachial index was 0.74±0.25, 
average Rutherford category was 3.15±0.78, and 17.7% presented with critical limb 
ischemia. Lesions were long (133.9±106.8 mm), and located mostly in the superficial 
femoral artery (85.3%), followed by the popliteal (13.2%), and posterior tibial artery 
(1.5%). In-stent restenotic (ISR) lesions comprised 47.1%, chronic total occlusions 
22.1%, and lesions with heavy calcification 27.9%. Procedural success was 94.1%. 
Additional stenting was performed in 25% lesions and 42.6% used embolic protection 
with the Nav-6 (Abbott Vascular, Santa Clara, CA) filter. There were 3 (4.4%) distal 
embolizations, all in unprotected cases that were successfully treated with aspiration-
thrombectomy. At 12-months post-procedure, target limb revascularization rate was 
20.6%, stent thrombosis 1.5%, and amputation-free survival 98.5%.  
Finally, a small feasibility study36 to assess the role of adjunctive balloon angioplasty 
after optimal debulking with JetStream was evaluated in 6 patients (total 15 lesions) with 
femoropopliteal instent restenosis. This demonstrated similar results to the porcine model 
above where maximum debulking was reached after 2 blades up mode but adjunctive 
balloon angioplasty added a significant increase in MLD post Jetstream (see figure 
below) 
 

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 24 of 68 
 
3.33 Reported Adverse Events 
Reported adverse events have been published (presented above). Unpublished AE/SAE 
can be found on the FDA webpage. 
 
4.0 METHODOLOGY 
4.1 STUDY DESIGN 
This is a prospective, multicenter (up to 14 sites), single arm study. Patients will be 
treated with plaque excision using JetStream XC (JS) followed by adjunctive balloon 
angioplasty (PTA). Each subject must meet all inclusion criteria and no exclusion criteria.  
A subject will be enrolled in the study only after angiography and confirmation of ISR in 
the FP segment.  All subjects will be followed up to 6 months after enrolment for the 
primary endpoint and 1 year for several secondary endpoints.  
 
Study Purpose  
The purpose of this study is to assess and estimate the effect of treating FP ISR with 
plaque excision using JS in combination with adjunctive PTA and compare this to 
historic control of PTA. 
4.2 
 PRIMARY OUTCOME 
Effectiveness 
Target Lesion Revascularization (TLR) at 6 months: TLR is defined as retreatment of 
the index lesion (extended 1 cm proximal and distal to the lesion) at 6 months. For the 
primary endpoint, intra-procedural bail out stenting of the index lesion is considered 
meeting a TLR endpoint. (Intention to treat Analysis analysis) 
Safety 
Major Adverse Events (MAE) at 30 days: unplanned amputation, total mortality or 
TLR at 30 days (TLR includes bail out stenting) 

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 25 of 68 
4.3 
  SECONDARY OUTCOMES 
 1. 
Device Outcome:  Categorized by < 50% residual stenosis following JS atherectomy alone 
and without additional adjunctive PTA or bail out procedures as determined by the 
Angiographic Core Laboratory. 
2. 
Procedural Outcome: Categorized by < 30% residual stenosis following the protocol-
defined treatment (JS + PTA) with provisional or bail out procedures as determined by the 
Angiographic Core Laboratory. 
3. 
Procedural Success: Defined as ≤30% residual diameter stenosis following JS + PTA 
without provisional or bailout procedures. 
4. 
Target Lesion Revascularization (TLR) at 6 months: TLR is defined as retreatment of 
the index lesion (extended 1 cm proximal and distal to the lesion) at 6 months. Intra-
procedural bail out stenting of the index lesion is NOT considered meeting a TLR endpoint. 
(ITT analysis) 
5. 
Target Lesion Revascularization (TLR) at 1 year: TLR is defined as retreatment of the 
index lesion (extended 1 cm proximal and distal to the lesion) at 1 year 
                                ITT (bail out stent in the Lab is considered as TLR)  
                      ITT (bail out stent in the Lab is not considered as TLR) 
6. 
Target Lesion Patency at 6 months and 1 year: Defined as PSVR ≤ 2.5 at the treated site 
or < 50% stenosis by angiography as determined by the Angiographic Core Laboratory  in 
the absence of TLR, amputation, and/or surgical bypass (the evaluation of patency is 
extended to one cm proximal and one cm distal to the target lesion) 
7. 
Clinically Driven Target Lesion Revascularization at 6 months and 1 year: Defined as 
any re-intervention or artery bypass graft surgery involving the target lesion in which the 
subject has a ≥ 70% diameter stenosis (Peak Systolic Velocity Ratio (PSVR) > 3.5 or on 
angiography) and at least two of the following:  worsening RCC by one category, worsening 
WIQ score by ≥20 points, or an ABI drop > 0.15 from baseline. 
                      ITT (bail out stent in the Lab is considered as TLR)  
                      ITT (bail out stent in the Lab is not considered as TLR)  
Routine angiography in an asymptomatic patient at 6 months or 1 year is not required in this 
protocol.  
 
8. 
Target Vessel Failure at 6 months and 1 year: Defined as major unplanned amputation 
related to the treated limb, vascular mortality related to treated limb and target vessel 
revascularization at 6 months  and 1 year (stenting in the lab is not considered a TLR/TVR) 
9. 
Target Lesion failure at 6 months and 1 year: Defined as major unplanned amputation 
related of the treated limb, vascular mortality related to treated limb and target lesion 
revascularization at 6 months and 1 year (stenting in the lab is not considered a TLR) 
10. Major Adverse Event Rate at 6 months and 1 Year: Defined as major unplanned 
amputation of the treated limb, all-cause mortality or TLR at 6 months and 1 year (bail out 
stent in the Lab is included as TLR) 
11. Change in WIQ Score at 6 Months and 1 Year: Defined as the change in Walking 

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 26 of 68 
Impairment Questionnaire (WIQ) score at 6 months and 1 year compared to baseline. 
12. Change in Rutherford Clinical Category at 6 Months and 1 Year:  Defined as the 
change in clinical status indicated by the change in RCC at 6 months and 1 year compared 
to baseline, that is attributable to the treated limb (in cases of bilateral disease).  
13. Change in Ankle-Brachial Index at 6 Months and 1 Year:  Defined as the change in the 
ankle-brachial index (ABI) at 6 months and 1 year compared to baseline in subjects with 
compressible arteries and baseline ABI < 0.9.  
14. Assisted Primary Patency rate at 1 year: Defined as < 50% stenosis per angiography as 
determined by the Angiographic Core Laboratory, or PSVR ≤ 2.5 at 1 year,  maintained by 
repeat percutaneous intervention of a restenotic but not occluded index lesion  
15. Secondary Patency rate at 1 year: Defined as < 50% stenosis per angiography as 
determined by the Angiographic Core Laboratory, or PSVR ≤ 2.5 at 1 year, maintained by 
repeat percutaneous intervention of a  restenotic or occluded vessel 
4.4 
      SUBJECT SELECTION CRITERIA 
Assessment of eligibility is based on data available to the Investigator at the time of 
subject enrollment. 
Patients with symptomatic peripheral arterial disease (Rutherford Becker Class II to 
IV) will be enrolled if they have been previously treated with stenting in the 
femoropopliteal segment and now return with suspicion of restenosis. There is no limit on 
how many times the target in-stent restenotic lesion has been previously treated. Also 
there is no exclusion based on how the prior treatment was done including if drug eluting 
balloons or stents have been used. Covered stents cannot be included however including 
Viabhan stents. There is no limit on the length of the target lesion as long as only one 
target lesion is treated and enrolled. If there is more than one target lesion per vessel, this 
will be considered an exclusion. Patients will be considered enrolled in the study 
following the index angiogram and if they are deemed by the operator to meet the 
inclusion criteria and none of the exclusion criteria and prior to commencement of any 
therapeutic intervention. In this study, and in order to ensure adequate representation of 
minority and ethnic groups affected by PAD, our target for the Black population will be 
about 15% of all patients enrolled and for females a minimum of 30% 
4.4.1 INCLUSION CRITERIA 
Subjects must meet all of the following criteria to be eligible to participate in this study: 
 
1. Subject is 18 years of age or older. 
2. Subject presents with clinical evidence of peripheral arterial disease with ISR 
in the femoropopliteal segment (includes common femoral, superficial 
femoral and popliteal) 
3. Subject presents with a Rutherford Classification of 2-4 and has symptoms of 
rest limb pain or claudication.  
4. Target lesion(s) must be viewed angiographically and have ≥50% stenosis. 

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 27 of 68 
5. The atherectomy wire must be placed entirely across all lesions to be treated 
with no visible evidence of clear or suspected subintimal/substent wire 
passage. 
6. The main target vessel reference diameter must be  5 mm and ≤ 7 mm 
7. One patent distal run-off vessel with <70% disease and with brisk flow is 
required. 
8. Intraluminal crossing of the lesion. If this is not certain, IVUS may be used to 
verify this per operator’s discretion 
9. Patient has signed approved informed consent. 
10. Patient is willing to comply with the follow-up evaluations at specified times. 
 
4.4.2 EXCLUSION CRITERIA 
 
Subjects will not be eligible to participate in the study if any of the following conditions are present: 
 
1. Subject is unable to understand the study or has a history of non-compliance with 
medical advice. 
2. Subject is unwilling or unable to sign the Informed Consent Form (ICF). 
3. Subject is currently enrolled in another clinical investigational study that might 
clinically interfere with the current study endpoints  
4. Subject is pregnant or planning to become pregnant within the study period. 
5. Subject has a known sensitivity to contrast media and the sensitivity cannot be 
adequately pre-medicated for.  
6. Subject is diagnosed with chronic renal failure or has a creatinine level > 2.5 
mg/dl and is not on chronic dialysis. 
7. Subject has a known allergy to heparin, ASA, Plavix.  
8. Subject has a history of bleeding disorders or platelet count < 80,000 cells/ml. 
9. Subject experiences ongoing cardiac problems (e.g., cardiac arrhythmias, 
congestive heart failure exacerbation, myocardial infarction, etc.) that, per the 
investigator, would not make the subject an ideal candidate for study procedures. 
10. Subject has a CVA or TIA within 4 weeks prior to JetStream procedure. 
11. Subject has an anticipated life span of less than 12 months. 
12. Subject is suspected of having an active systemic infection. 
13. Limited vascular access that precludes safe advancement of the Jetstream XC 
System to the target lesion(s). 
14. Patient has evidence of intracranial or gastrointestinal bleeding within the past 3 
months. 
15. Patient has had severe trauma, fracture, major surgery or biopsy of a parenchymal 
organ within the past 14 days. 
16. Patient has any planned surgical intervention or endovascular procedure ≤ 30 days 
after the index procedure. 
17. Use of another debulking device during the index procedure prior to the Jetstream 
XC System. 
18. Use of another debulking device after the Jetstream XC system.  
19. Class III and IV fractures 
20. Stents not fully apposed to vessel wall or overlapping stent segments 

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 28 of 68 
21. Target lesion previously treated with a covered stent (such as Viabhan stent) 
4.43   STUDY TREATMENT RULES 
1. No other debulking devices, cutting/scoring balloons or cryogenic balloons 
may be used in before or after the Jetstream XC 
2. Balloon inflation is per operator’s discretion but should not exceed burst 
pressure and should be at least at nominal pressure. Operators should increase 
balloon pressure beyond nominal pressure only if balloon full expansion does 
not occur at nominal pressure. If higher balloon pressure beyond nominal is 
felt necessary, then pressure is increased at 1 atm every 5 seconds until full 
balloon expansion occurs.  
3. Semi-compliant balloons are recommended  
4. The only adjunctive therapies allowed are PTA and bailout stenting: 
 Bailout stenting is allowed  if > 30% residual stenosis remains or 
for perforation 
 Type D dissection leading to flow limitations 
 Self-expanding nitinol stents are recommended if needed  
 Covered stents are allowed only if there is a perforation 
 Bailout stenting is not allowed if the lesion has ≤ 30% residual 
stenosis 
 Only one leg may be treated per patient. Patient is enrolled only 
once in the study.   
 Drug coated stents or Drug coated balloons are not allowed.  
4.44    GENERAL EXCLUSION CRITERIA 
The subject must not meet any of the following general exclusion criteria. 
1. Has one or more of the contraindications listed in the JetStream IFUs. 
2. Patient has already been enrolled once in the protocol 
3. Has a contraindication or known untreated allergy to antiplatelet therapy, 
anticoagulants, thrombolytic drugs or any other drug anticipated to be used (that 
cannot be reasonably substituted). 
4. Has known hypersensitivity to treatment device materials including nitinol. 
5. Has known uncontrollable hypercoagulable condition, or refuses blood 
transfusion. 
6. Has surgical or endovascular procedure of the target or non-target vessel within 
30 days prior to the index procedure.  
7. Has had a previous peripheral bypass affecting the target vessel (allowable for 
physician to pass through bypass graft in aorta-iliac region to get to the target 
lesion).  
8. Has had superficial thrombophlebitis or deep venous thrombus within 30 days 
prior to index procedure. 

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9. Has history of significant gastrointestinal bleeding in the past 1 month prior to 
index procedure, or any history of hemorrhagic diathesis. 
10. Patients with ipsilateral Iliac and CFA disease are allowed in the study but these 
lesions have to be treated successfully first (<30% residual) before patient can 
be enrolled. Treatment as per investigator’s preference.  
11. Lesions have to be separated by > 5 cm in order to be considered different 
lesions. Only one lesion per target vessel can be enrolled during the index 
procedure 
 
4.45    PATIENT SCREENING 
It is recommended that all eligible patients be approached for enrollment in the study and 
be screened at the study site.  Study personnel will explain to the patient that even if the 
patient agrees to participate in the study and signs the written informed consent, 
angiography may demonstrate that the patient is not a suitable candidate for the study.   
4.46   SUBJECT ENROLLMENT 
The subject is enrolled in the study after he/she has signed the subject informed consent 
and it has been determined that he/she meets all of the inclusion criteria and none of the 
exclusion criteria.  The point of enrollment is defined as the moment an exchangeable 
guidewire and treatment catheter cross the target lesion in the true lumen.   
4.47 BLINDING 
Blinding is not possible in this one arms study 
4.48 OVERVIEW OF STUDY CONDUCT 
The Table 1 provides an overview of the assessment requirements for the study.  All 
testing and assessments should be conducted at the study site.   

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 30 of 68 
Table 1: Study Assessment Requirements  
 
Follow-Up Visits 
 
Baseline 
Procedure 
Pre-
Discharge 
30-Day 
6-Month 
1-Year 
 
Within 45 
days prior to 
enrollment 
 
Prior to discharge 
(or within 5 days 
after index 
procedure) 
30-45 days after 
index procedure 
150-210 days 
after index 
procedure 
320-410 days 
 after index 
 procedure 
Informed Consent  
X 
 
 
 
 
 
Medical History and Physical Exam 
X 
 
 
X 
X 
X 
Medication Use 
X 
 
 
X 
X 
X 
Creatinine (non-standardized) 
X 
 
X^ 
 
 
X 
Hemoglobin A1C 
X† 
 
 
 
X 
Rutherford Clinical Category 
Assessment 
X 
 
 
X 
X 
X 
Walking Impairment Questionnaire 
(WIQ) 
X 
 
 
X 
X 
X 
Ankle Brachial Index (ABI) 
X 
 
 
X 
X 
X 
Angiogram 
 
X 
 
 
 
 
Duplex Ultrasound 
 
 
X* 
X 
X 
Adverse Event Evaluation 
 
X 
X 
X 
X 
X 
† Blood draw for hemoglobin A1C assessment can occur at the baseline evaluation or during the procedure. 
* The first duplex ultrasound can occur any time within 45 days of the index procedure. 
^ Cr at 72 hours post procedure +/- 24 hours 
4.49 REQUIRED ASSESSMENTS AND TESTS  
The following section details the study-required assessments and tests.   
4.50 MEDICAL HISTORY AND PHYSICAL EXAMINATION 
The subject’s clinical history and pre-existing conditions will be assessed and 
documented at baseline and at every visit at 30 days, 6 months and 1 year. 
4.51 MEDICATION USE   
The subject’s medication use will be documented at baseline, at 30 days, 6 months and 1 
year.  Medication use will include anticoagulants and antiplatelet medications.    
4.52 CREATININE   
Creatinine (non-standarized) will be obtained and documented at baseline, 72 hours post 
procedure (+/- 24 hours) and at 1-year follow-up visit.   

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4.53 HEMOGLOBIN A1C (HB A1C) 
Glycosylated hemoglobin (Hb A1C) will be obtained and documented at either baseline 
or on the day of the procedure, and at the 1-year follow-up visit.   
4.54 RUTHERFORD CLINICAL CATEGORY ASSESSMENT  
The subject’s clinical status as indicated by RCC per clinical description will be assessed 
and documented at baseline and all follow-up visits.   
4.55 ANKLE-BRACHIAL INDEX (ABI)  
The subject’s ABI will be measured and documented at baseline and all follow-up visits.  
An ABI is the ratio of the highest ankle systolic pressure to the highest brachial systolic 
pressure.   
4.56 WALKING IMPAIRMENT QUESTIONNAIRE (WIQ)  
Each subject will undergo a WIQ assessment and the results will be documented at 
baseline and all follow-up visits.  The WIQ is an interviewer-administered subject-
reported functional assessment focused on difficulty in walking.   
4.57 ANGIOGRAM 
For procedural angiogram requirements see Section 4.62.  Angiograms will be obtained 
per the Angiographic Protocol determined by the Angiographic Core.  
4.58 DUPLEX ULTRASOUND (DUS) 
It is required that the subject undergo a DUS, the results be documented and copies of the 
scan be sent to the core laboratory.  DUS is required within 45 days of the index 
procedure (at either the pre-discharge or 30-day visit), at 6 months, and at 1 year post-
procedure. DUS will be obtained as per Core lab protocol.    
4.59 ADVERSE EVENT (AE) EVALUATION  
Adverse event evaluations will be performed during the procedure, prior to discharge, 
and at all follow-up visits.  Refer to Section 4.20 and 4.3 and Definition section for AE 
definitions.  
4.60 BASELINE REQUIREMENTS 
Informed consent must be obtained from each subject prior to enrollment into the study in 
accordance with the ICH/GCP guidelines, Declaration of Helsinki, and pertinent 
individual country laws/regulations.   
Table 2 summarizes the list of all assessments and tests that are required at baseline.  The 
blood sample for the assessment of creatinine will be taken at baseline.  The blood 
sample for the hemoglobin A1C test may be taken at baseline or during the procedure.   
Table 2: Baseline Requirements 
Baseline Requirements 
Timeframe Window 

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Informed consent  
Within 45 days prior to enrollment 
Medical history and physical exam 
Creatinine 
Hemoglobin A1C† 
Concomitant medication use 
Rutherford Clinical Category assessment 
Walking Impairment Questionnaire (WIQ) 
Ankle Brachial Index (ABI) 
† Blood draw for hemoglobin A1C assessment can occur at the baseline evaluation or during the procedure. 
4.61 PROCEDURE REQUIREMENTS 
The subject will undergo percutaneous revascularization of the superficial femoral and/or 
popliteal arteries. The JS + adjunctive PTA will be used to treat all lesion. Operators 
should have at least a minimum experience with 10 Jetstream cases as a primary operator 
to qualify to enroll patients in this study.  
The following describes the required assessments and activities during the procedure.   
4.62 ANGIOGRAM  
A sheath will be inserted and after insertion the subject should receive anticoagulation 
medications as indicated by the Investigator to maintain appropriate clotting time.  
Selective angiography of the limb to be treated including the distal aorta, bilateral iliac, 
ipsilateral femoral, popliteal and tibial-peroneal vessels (to the pedal level) will be 
performed to identify the anatomical characteristics of the vasculature and to best isolate 
and define the lesion.  If a pre-procedure assessment has been completed with 
CTA/MRA, the angiography can be limited to the target vessel, with a baseline 
assessment of run-off.  Angiography must be conducted according the Angiographic 
Protocol (refer to Core Lab requirement).  Gadolinium and CO2 are not allowed for use 
as contract material. 
During angiography the Investigator performing the procedure will assess the subject for 
the angiographic inclusion and exclusion criteria.  It is required that a radiopaque ruler be 
used to define lesion length and define anatomical measurement references.  If the subject 
meets all the angiographic inclusion criteria and does not meet any of the angiographic 
exclusion criteria, the subject is enrolled when an exchangeable guidewire crosses the 
target lesion.  Upon enrollment, subjects will be then treated with the JS + PTA as per 
protocol.  
Angiographic films, including run-off, will be obtained immediately prior to and after 
treatment (after JS alone, and after adjunctive PTA or bail out stenting) according to the 
Angiographic Core Lab Protocol.  Capture images that demonstrate the stenosis in two 
views that minimize the degree of vessel overlap and demonstrate the stenosis in its most 
severe view.  Angiographic results must be sent to the Angiographic Core Laboratory. 
The Angiographic Core Laboratory assessments will supersede the measurements by the 
Investigator performing the procedure for data analysis purposes; however, the 

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measurements by the Investigator performing the procedure will be used to determine 
subject eligibility at the time of enrollment.   
The Angiographic core laboratory will also assess stent fracture location and severity at 
baseline prior to any treatment and post atherectomy to assess for additional/worsening 
fractures. 
4.63 TREATMENT OF THE TARGET VESSEL 
4.641 TARGET LESION 
The lesion intended for treatment at the time of the index procedure that meets the 
inclusion criteria and none of the exclusion criteria will be considered the “target lesion.”  
Each subject can have only one target lesion.  The point of enrollment is defined as the 
moment an exchangeable guidewire and treatment catheter cross the target lesion in the 
true lumen.  
If there are 5 cm or less between diseased segments needing treatment in the SFA and/or 
popliteal artery, then it can be considered one lesion (see example below).  If there are 
more than 5 cm between diseased segments, they will be considered separate lesions and 
count as two or more lesions.  If multiple lesions in the target vessel require treatment, 
patient not eligible for enrolment  
 
 
4.642 TREATMENT OF NON-TARGET VESSELS 
Lesions in the ipsilateral or contralateral iliac arteries or ipsilateral common femoral 
arteries to the target limb that require treatment may be revascularized during the index 
procedure. These lesions must be successfully treated prior to the point of enrollment. 
Stent placement in the common femoral arteries will exclude patient from enrolment. 
If a patient has an infrapopliteal lesion that requires treatment for significant (> 70% 
stenosis or occlusion) stenosis, patient cannot be enrolled.  
Lesions in the non-target limb may be treated during the index procedure, but not within 
or equal 30 days following the index procedure.   
4.643 JS + PTA GROUP PROCEDURES  
The selection of the JS XC device will be at the discretion of the treating physician.  In 
general however, the 2.4 XC is for vessel diameter > 5 cm and 2.1 XC for 4-5 cm. The 
plaque excision procedure will follow the steps described in the published manual by 
Shammas et al.2 The Spartacore (Abbott) or JetStream Wire (Boston Scientific) are 
recommended with the use of the JetStream device. The Grand Slam wire and 
hydrophilic wires are not recommended. Filters are highly encouraged but left to 
investigator’s discretion. If a filter is used, the off label use of the Nav-6 (Abbott) filter is 
7 cm
5 cm
5 cm
17 cm
Single lesion: 17 cm lesion since separation is ≤ 5.0 cm 

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recommended. The long BareWire will need to be used. JetStream IFU has no 
recommendations on filter use.  
Residual stenosis following the plaque excision treatment must be documented by 
angiography per the Angiographic Protocol. It is recommended that residual stenosis be < 
50% prior to treatment with adjunctive PTA.   
Dilation of the lesion following JS has to be done with a 1:1 balloon size and avoidance 
of oversizing.  The diameter of the study balloon will be selected based on the vessel 
reference diameter distal to the target lesion. Balloon inflation should be limited to within 
the stent. See section 4.43 for details.    
If there is a complication during JS, treatment is at the operator’s discretion.  If a 
perforation occurs in the area of plaque excision, it must be sealed and distal outflow 
must be established.  
4.644 ADJUNCTIVE PROCEDURES  
Adjunctive procedures besides PTA should be avoided if possible.  In the event of a 
major flow limiting dissection (type D and higher), perforation, or occlusive complication 
(e.g., recoil), prolonged balloon inflation (5 minutes) must be attempted first.  All efforts 
should be made to eliminate the need for bail-out stent placement.  In cases where the 
results after prolonged balloon inflation are suboptimal, bail-out stenting is allowed.  A 
cine following the prolonged balloon inflation must be captured; all bail-out stenting 
procedures will be reviewed by the Angiographic Core Laboratory.  Adjunctive treatment 
with cutting balloons or scoring balloons is not allowed. Adjunctive or primary PTA 
should be done with a non-compliant or semi compliant balloon sized 1:1 to vessel size. 
Adjunctive stenting is performed only with self-expanding nitinol stent. Drug coated 
stents, covered stents, or drug coated balloons are not allowed in the study.  
4.645 PROCEDURE COMPLETION 
An angiogram of the treated segment(s) must be recorded for subsequent Angiographic 
Core Laboratory analysis of the post-treatment residual stenosis.  
The end of the procedure is defined as the time after a complete angiogram, including 
runoff, has been performed AND the last guidewire and catheter have been removed.  If 
the subject returns to the procedure room and a guiding catheter is reinserted and dilation 
is performed, this is considered a re-intervention and should be documented accordingly.  
The sheath(s) may be removed at the physician’s discretion. 
4.646 ADVERSE EVENT EVALUATION  
An AE evaluation will be performed during and at the end of the procedure.  See Section 
4.20 for the AE definitions.  Adverse event evaluations will also occur prior to discharge 
and at all follow-up visits.   

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4.647 MEDICAL ANTICOAGULANT/ANTIPLATELET THERAPY  
Pre-Procedure 
The subject should be optimally medically-managed for peripheral arterial disease per the 
standard institutional regimen.  
Peri-Procedure 
The subject should receive anticoagulation as indicated by the Investigator to maintain 
appropriate activated clotting time (ACT). For patients receiving bivalirudin, ACT is not 
necessary. For patients receiving heparin, the ACT goal is 250 seconds (Using iStat) or 
300 seconds using Hemochron. If patient is on clopidogrel or other ADP receptor 
antagonist, this will be continued as prescribed. If patient is on Ticagrelor, only 81 mg of 
ASA daily should be prescribed. If patient is not on ADP receptor antagonist, he will be 
loaded with clopidogrel 600 mg po x one dose (or equivalent drug).  
Post-Procedure 
The subject should be optimally medically-managed for peripheral arterial disease per the 
standard institutional regimen. Post procedure, patients should be continued on 
clopidogrel (or an equivalent drug) 75 mg po daily for 3 months and aspirin indefinitely. 
If patient is on ticagrelor, asa 81 mg po daily is prescribed.  
4.648 FOLLOW-UP REQUIREMENTS 
All subjects are required to complete all follow-up visits as shown in Figure 2. 
 
 
 
 
 
Figure 2:  Study Diagram of Follow-up Requirements 
 
4.649 PRE-DISCHARGE FOLLOW-UP REQUIREMENTS 
All subjects are required to have a pre-discharge assessment.  Pre-discharge assessment 
requirements are listed in Table 3. 
 
Table 3: Pre-Discharge Assessment Requirements 
Pre-Discharge Requirements 
Timeframe 
Adverse event evaluation 
Prior to discharge (or within 5 days 
after index procedure) 
Duplex Ultrasound* 
Index 
Procedure 
for All 
Enrolled 
Subjects 
Pre-
Discharge 
Follow-up  
(prior to 
discharge or 
within 5 
days after 
index 
procedure) 
30-Day 
Follow-up 
Visit 
(30-45 days 
after index 
procedure) 
6-Month 
Follow-up 
Visit 
(150-210 
days after 
index 
procedure) 
 
12-Month 
Follow-up 
Visit 
(320-410 
days after 
index 
procedure) 

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* First duplex ultrasound can occur any time within 45 days of the procedure.  Must be conducted per Duplex 
Ultrasound Protocol.  Copies must be sent to the Duplex Ultrasound Core Laboratory for review. 

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4.650 FOLLOW-UP VISIT REQUIREMENTS 
All subjects are required to have a follow-up visit at 30 days, 6 months, and 1 year post-
procedure.  Tables 4-6 below list the follow-up assessment requirements and visit 
windows, according to number days following the index procedure.  
Table 4: 30-Day Follow-Up Visit Requirements  
Follow-up Requirements 
Target 
Window 
Rutherford Clinical Category assessment 
30 Days 
30-45 Days 
Ankle-brachial index 
WIQ  
Duplex Ultrasound* 
Adverse event evaluation 
* First duplex ultrasound can occur any time within 45 days of the procedure. Must be conducted 
per Duplex Ultrasound Protocol.  Copies must be sent to the Ultrasound Core Laboratory for review. 
Table 5: 6-Month Follow-Up Visit Requirements 
Follow-up Requirements 
Target 
Window 
Rutherford Clinical Category assessment 
180 Days 
150-210 
Days 
Ankle-brachial index 
WIQ  
Duplex Ultrasound* 
Adverse event evaluation 
*Must be conducted per Duplex Ultrasound Protocol.  Copies must be sent to the Duplex Ultrasound 
Core Laboratory for review.  
 
Table 6: 1-Year Follow-up Visit Requirements 
Follow-up Requirements 
Target 
Window 
Hemoglobin A1C 
365 Days 
320-410 
Days 
Creatinine 
Rutherford Clinical Category assessment 
Ankle-brachial index 
WIQ  
Duplex Ultrasound* 
Adverse event evaluation 
*Must be conducted per the Core Laboratory Protocols.  Copies must be sent to the Core Laboratories 
for review.  
4.651 UNSCHEDULED AND RE-INTERVENTION VISITS DURING FOLLOW-UP 
Completion of study assessments at unscheduled follow-up visits prior to the 1-year visit 
should be done as clinically indicated and corresponding data should be documented and 
submitted to the Sponsor. 

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If a subject is clinically indicated for a re-intervention of the target lesion prior to the 1-
year follow-up visit and the subject does not want to proceed with an invasive angiogram 
or re-intervention, it will not be considered a deviation from the Study Protocol.   If 
possible, all non-invasive assessments should be captured for the study, including ABI, 
RCC, WIQ, and duplex ultrasound, even if the re-intervention and angiogram are 
declined.  Copies of any angiographic or duplex ultrasound results must be sent to the 
appropriate core laboratory. These data will be collected and used for adjudication by the 
Clinical Event Committee for “clinically-driven” reintervention. 
The investigator will initially determine the lesion severity by visual 
estimate prior to re-intervention. The cine angiogram will be sent to 
angiographic core lab for analysis. Two orthogonal views of the lesion 
will be required to determine more accurately the lesion severity by the 
core lab. Core lab evaluation of lesion severity will be used as the 
more definitive measure and supersedes operator's visual estimate.  
The following describes what take precedence (angiogram versus duplex 
ultrasound) to determine lesion severity:1. Patient has both modalities 
because of symptoms recurrence prior to 6 months follow up. To be 
consistent with the 6 months’ primary endpoint the Duplex ultrasound 
will take precedence 
2. Patient has angiogram only because of symptom recurrence prior to 6 
months. In this case the angiographic finding of loss of patency will be 
used as no Duplex ultrasound was performed. The Duplex ultrasound at 6 
months post reintervention will not be used even if performed as it is 
post re-intervention.  
3. Patient undergoes both modalities at 6 months because of symptoms. 
Duplex ultrasound will take precedence as long as it has been done prior 
to the angiogram and re-intervention. 
 
4.652 TERMINATION OF PARTICIPATION 
All subjects have the right to withdraw from participation at any point during the study.  
In addition, Principal Investigators also have the ability to terminate subject participation 
in the study.  A description of the reason for a subject’s termination will be documented.  
Reasons for termination include: subject withdrawal, physician-directed subject 
withdrawal, and lost-to-follow-up.   
4.653 LOST TO FOLLOW-UP 
Every attempt must be made to have all subjects complete the required follow-up visits 
according to the visit schedule.  A subject will not be considered lost-to-follow-up unless 
efforts to obtain compliance are unsuccessful.  At a minimum, the effort to obtain follow-
up information must include three attempts to make contact via telephone.  Telephone 
contact efforts to obtain follow-up must be documented in both the subject’s medical 
records and on the study electronic case report forms (eCRFs).   

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4.654 SUBJECT WITHDRAWAL 
Whenever possible, the site staff should obtain written documentation from the subject 
that wishes to withdraw his/her consent for future follow-up visits and contact.  If the site 
staff is unable to obtain written documentation, all information regarding the subject’s 
withdrawal must be recorded in the subject’s medical record.  In addition, the appropriate 
eCRFs must be completed for the subject and clear documentation of the subject’s 
withdrawal must be provided to the Sponsor.   
Withdrawal of a subject from the study can occur at the discretion of the Principal 
Investigator or the Sponsor.  Reasons for physician and/or Sponsor-directed subject 
withdrawal include, but are not limited to: the subject is not adhering to the Study 
Protocol requirements, the subject has enrolled in another study that conflicts with this 
Study Protocol outcomes, or if it is in the best interest for the safety or welfare of the 
subject to withdraw. 
4.655 DEVIATIONS TO THE STUDY 
Principal Investigators and site staffs should avoid Study Protocol deviations. Any 
deviations from clinical protocol requirements will be considered protocol deviations and 
need to be reported to the Sponsor.  Any emergency deviations (deviations from the 
Study Protocol to protect the life or physical well being of a subject, such as, surgical 
repair of the target vessel) that occur must be reported to the Sponsor and the site Ethics 
Committee (EC) per their local guidelines.   
4.656 ADVERSE EVENTS 
4.657 ADVERSE EVENT DEFINITIONS 
 
Serious Adverse Event (SAE) is defined as any untoward and unintended clinical sign, 
symptom, or disease in a subject, regardless of the relationship between the adverse event 
and the device under investigation, that: 
 Led to a death,  
 Led to a serious deterioration in the health of the subject that: 
1. Resulted in a life-threatening illness or injury,  
2. Resulted in a permanent impairment of a body structure or a body function,  
3. Required inpatient hospitalization or prolongation of existing hospitalization, 
or  
4. Resulted in medical or surgical intervention to prevent permanent impairment 
to a body structure or body function.   
 Led to fetal distress, fetal death or a congenital abnormality or birth defect.   
A written report must be provided to the Sponsor or representative within 24 hours of the 
Investigator learning of an SAE and must be provided to the EC according to reporting 
guidelines. 

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4.658 ADVERSE EVENT CLASSIFICATIONS 
In addition to the definitions above, adverse events will be classified as follows: 
Major Adverse Events 
1. Major Adverse Events (MAE) as individual endpoints in-hospital and 
up to 30 days :  Include device-induced vascular injury as reported by the 
operator, amputation (major and minor unplanned), death, significant 
distal embolization requiring the use of pharmacologic or mechanical 
means to treat (other than a vasodilator), perforation (extravasation of 
blood outside the vessel wall), major bleeding, non-fatal myocardial 
infarction (defined as the occurrence of more than 20 minutes of chest 
pain post procedure with an increase in troponin), stroke, access 
complications (AV fistula and pseudoaneurysm), bail out stenting, acute 
renal failure (drop in crcl by > 25% from baseline), acute (< 24 hours) or 
subacute (< 1 month , > than 24 hours) vessel closure. 
2. Target Lesion failure at 6 months and 1 year: Defined as major 
unplanned amputation related of the treated limb, vascular mortality 
related to treated limb and target lesion revascularization at 6 months and 
1 year (stenting in the lab is not considered a TLR) 
3. Major Adverse Event Rate at 6 months and 1 Year: Defined as major 
unplanned amputation of the treated limb, all-cause mortality or TLR at 6 
months and 1 year (bail out stent in the Lab is included as TLR) 
 
Unanticipated or Unexpected Adverse Device Effects:  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 protocol or application (including a supplementary plan or 
application), or any other unanticipated serious problem associated with a device that 
relates to the rights, safety, or welfare of subjects. 
4.659 ADVERSE EVENT RELATIONSHIPS 
The Investigators will evaluate whether or not the adverse events were related to the 
procedure, study requirements, and/or investigational products (e.g., JS device, 
angioplasty balloon, drug coating) according to the following categories: 
Related:  AE that has a strong temporal relationship to the study procedure, a study 
requirement, or the presence or performance of the investigational device/system or drug 
and an alternative etiology is highly unlikely. 
Possibly Related:  AE that has a temporal relationship to the study procedure, a study 
requirement, or the presence or performance of the investigational device/system or drug 
and an alternative etiology is unlikely. 

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Not Related:  AE is due to the underlying disease state or concomitant medication or 
therapy, and was not caused by the study procedure, a study requirement, or the 
investigational device/system or drug. 
Not Assessable:  It is not possible to assess whether or not the adverse event is related to 
the study procedure, a study requirement, or the investigational device/system or drug. 
4.660 DEATHS 
Each subject death must be reported to the Sponsor.  A death must be reported to the 
Sponsor or representative as soon as possible (within 24 hours) after the site’s knowledge 
of the event.  A written report will be provided to the Sponsor within 10 business days 
after the Investigator learns of a death and will be provided to the EC according to 
reporting guidelines.   It is requested that a copy of the death certificate, autopsy report, 
and any other source documents related to the death be sent to the Sponsor or 
representative when available.  In the event that no source documents are available, the PI 
will be required to submit a letter to the Sponsor describing the circumstances of the 
subject’s death. 
4.661 CORE LABORATORY REQUIREMENTS 
4.662 ANGIOGRAPHIC CORE LABORATORY 
An independent Angiographic Core Laboratory will review all scheduled and 
unscheduled angiographic procedure data.  See Core Lab Angiographic Protocol.  
4.663 ULTRASOUND CORE LABORATORY 
An independent Ultrasound Core Laboratory will review all scheduled and unscheduled 
duplex scans and intravascular ultrasounds.  See Core Lab Duplex Ultrasound Protocol.   
4.664 CLINICAL EVENTS COMMITTEE 
An independent Clinical Events Committee (CEC) will be established.  The CEC will 
consist of physicians who are not Investigators in the study and who do not have any 
significant investment in Boston Scientific, Bard or any of their entities.  The committee 
may include, but not be limited to, the specialties of interventional cardiology, vascular 
surgery, and interventional radiology. 
The CEC is responsible for reviewing all reported adverse events. The CEC will classify 
the pertinent outcome events as defined in the Study Protocol.   
4.665 DATA SAFETY MONITORING BOARD  
An independent Data Safety Monitoring Board (DSMB) will be established.  The DSMB 
will consist of a biostatistician and physicians from a variety of relevant medical 
specialties, including interventional cardiology, vascular surgery, and interventional 
radiology, who are not Investigators in the study.  Members will not have any significant 
investment in Boston Scientific or Bard, or any of their entities. 

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The role of the DSMB will be to monitor and make recommendations regarding the 
protocol and the overall conduct of the study, to ensure the rights, safety, and welfare of 
the study participants, and to evaluate interim data to determine if there are any specific 
safety concerns.   
The DSMB will convene when 30-day safety data are available for 100 randomized 
subjects.  Subsequently, the DSMB will review the data at time intervals per their 
discretion.  
4.666 CASE REPORT FORMS 
Electronic case report forms (eCRFs) and paper CRF will be used to collect study data.  
The eCRFs will be reviewed and signed by the Principal Investigator attesting to their 
accuracy.  All appropriate sections of the CRFs must be completed.   
The Sponsor will use the study data for statistical and tracking purposes and will treat the 
information as confidential.   
5.0 STATISTICAL METHODS  
 
5.1 SAMPLE SIZE  
 
5.11 Meta-analysis of PTA control arms from randomized trials 
 
Please refer to Appendix A at end of protocol  
 
5.12 Assumptions: 
 
TLR with bailout stenting from historic control from meta-analysis:  
37.9% 
TLR with bailout stenting from Jetstream ISR feasibility study: 
 
20.7% 
Power 80% 
Alpha 0.05 
 
We are planning a study of independent cases and controls with 1 control(s) per 
case.  Prior data indicate that the failure rate among controls is 0.38.  If the true failure 
rate for experimental subjects is 0.21, we will need to study 112 experimental subjects 
and 112 control subjects to be able to reject the null hypothesis that the failure rates for 
experimental and control subjects are equal with probability (power) 0.8 (meta-analysis 
from published randomized trials provides data on 182 controls).   The Type I error 
probability associated with this test of this null hypothesis is 0.05.  We will use an 
uncorrected chi-squared statistic to evaluate this null hypothesis. Assumingly a loss of 
20% of patients on follow-up a minimum of 134 patients will be enrolled.  
 
.  

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5.2 DATA ANALYSIS PLAN 
5.23 GENERAL PRINCIPLES 
All statistical analyses will be performed using a widely accepted statistical or graphical 
software.  An intention to treat analysis will be carried on with bailout stenting as TLR 
and without bail out stenting as TLR. Also analysis will be done by actual treatment. A 
maximum of 140 patients will be enrolled. 
Descriptive statistics will be used to present the data and to summarize the results.  
Discrete variables will be presented using frequency distributions and cross tabulations.  
Continuous variables will be summarized by presenting the number of observations (N), 
mean, standard deviation, median, minimum, and maximum values.    
For AE reporting, the primary analysis will be based on subject counts.  A subject with 
more than one event will be counted only once toward the event rate based on the total 
number of subjects with AEs.  An event rate based on event counts will also be 
presented.  For example, if a subject experiences one major unplanned amputation of the 
treated limb and two clinically-driven TLRs within 30 days, the subject will be counted 
once in the rate of total subjects with a 30-day MAE; the same subject will be counted 
once in the individual event category of “Major Unplanned Amputation of the Treated 
Limb” and twice in the “Clinically-Driven TLR” category.     
5.24 ANALYSIS OF BASELINE DEMOGRAPHICS AND PROCEDURAL CHARACTERISTICS 
Descriptive analysis will be performed on all clinically relevant baseline demographics 
and procedural variables using percentages for dichotomous variables and mean +/- 
Standard deviations for continuous variables 
5.25 ANALYSIS OF OUTCOMES   
We hypothesize that JetStream atherectomy is superior to plain old balloon angioplasty in 
treating femoropopliteal in-stent restenosis in regards to the primary effectiveness 
endpoint of target lesion revascularization at 6 months with bailout stenting considered as 
a TLR. The Null Hypothesis assumes that the active control (JetStream) and the historic 
control of TLR (derived from the meta-analysis) have the same TLR at 6 months by 
intention to treat analysis. We calculated that if TLR is 0.38 for balloon angioplasty and 
0.21 for JetStream, we need a total of 112 experimental subject and 112 control to reject 
the null hypothesis with a power of 0.8 and alpha of 0.05. The meta-analysis has provided 
data on TLR for balloon angioplasty in more than 112 controls. To account for patient 
loss to follow up we plan to enroll a maximum number of 140 patients in this study 
5.26 ANALYSIS OF ABILITY TO POOL DATA ACROSS INVESTIGATIONAL SITES 
This is a multi-center clinical study with standardization of subject enrollment, data entry 
and adverse event reporting.  All investigational sites will follow the requirements of a 
common protocol, and common data collection procedures and forms.  To present the 
data from this clinical study in a summary form, a comparison across all sites will be 
completed to determine if the generated data can be pooled.  

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Potential site effects on the primary outcome will be explored.  In addition, a comparison 
of variables will be completed to assess the appropriateness of pooling data from across 
all sites.  
6.0 RISK/BENEFIT ANALYSIS 
 
 
The study is designed to minimize risk through observance of strict site and Investigator 
selection criteria, careful subject selection and management, and rigorous adherence to a 
standardized schedule of post-procedure evaluations. The recommendations in the IFU 
will be used for wire selection.  
6.1 POTENTIAL BENEFITS 
There are no guaranteed benefits from participation in this study; however, it has been 
shown that treatment with plaque excision improves blood flow through the treated artery 
in some patients.  Information gained from the conduct of this study may be of benefit to 
other persons with the same medical condition.   
6.2 POTENTIAL RISKS  
6.3 RISKS ASSOCIATED WITH PLAQUE EXCISION 
The risks associated with JS atherectomy of the SFA and/or popliteal artery may include, 
but are not limited to, the following: 

MCRF-S-002-2016, Version 2.0                              29 February 2016                            Page 45 of 68 
 Access site complications  
 Amputation 
 Arterial dissection 
 Arterial perforation  
 Arterial rupture  
 Arterial spasm  
 Arterial thrombosis 
 Arterio-venous (AV) fistula 
 Bleeding complications  
 Death  
 Embolism 
 Device getting stuck on stent 
 Wire breaking during 
atherectomy 
 Emergency or non-emergency 
arterial bypass surgery  
 Hypotension  
 Infection  
 Ischemia  
 Restenosis of the treated 
segment  
 Total occlusion of the 
peripheral artery  
 Vascular complications which 
may require surgical repair  
 Disruption of previously 
implanted stent
 

 
46 
 
As with any device requiring mechanical deployment and retraction, there exists a risk of 
mechanical failure of the device resulting in potential surgical intervention. 
All of the above could cause prolonged illness, permanent impairment of daily function or, in 
rare cases, death.  Possible treatments could include, but are not limited to, vascular surgery. 
Extensive reliability engineering testing has been performed on the study device to mitigate risks 
to the subject due to product failure.  Additionally, studies using the JS device have been 
conducted to ensure that the systems perform as intended without introducing more risks during 
the index procedure or during follow-up.  Risks of atherectomy may be further limited by 
providing medications such as aspirin or clopidogrel and continuing to monitor subjects 
following treatment.   
While some of the potential risks identified have occurred in prior atherectomy trials, and while 
Boston Scientific believes that the risk for significant injury or death due to the JS XC device is 
quite low, these risks have yet to be adequately and fully quantified.   These risks in applying  
the JS to  in-stent restenosis has not been defined in a large trial  but early preclinical  data and 
the JetStream ISR feasibility study has  shown that the device performed safely with no  device-
stent interaction.   
 
 
6.4 RISK MITIGATION  
 
 
The CEC committee will adjudicate every adverse events and unexpected device related events. 
DSMB will meet at completion of the first 30 patients and at 60 patients to analyze   procedural 
and follow up events. Recommendations will be made to continue or stop the study based on 
these 2 interim analysis.  All investigators will have to prove experience with at least 10 
Jetstream cases with no significant events. Also, investigators will be trained on the protocol to 
ensure adherence to the inclusion and exclusion criteria and for timely reporting of adverse 
events as recommended by the IRB and FDA. Subjects will learn about the protocol from 
investigators and designated coordinators. Voluntary participation will be emphasized. Patients 
will sign informed consent form (see Appendix C for the ICF).  
 
 
7.0 SITE REQUIREMENTS 
 
7.1 SITE SELECTION  
The Sponsor or a representative of the Sponsor will evaluate each potential site to ensure the 
Principal Investigator and his/her staff has the facilities and expertise required for the study. 
Principal Investigators, Sub-Investigators and sites will be selected based upon the following 
factors, including, but not limited to: 
 Previous experience with clinical research and percutaneous procedures, including 
experience treating lower extremity arteries with the JS device  

 
47 
 
 Currently treating patients who meet the inclusion/exclusion criteria 
 Ability to enroll an adequate number of subjects in the study 
 Ability to perform required clinical testing, including angiography, and duplex 
ultrasound 
 Ability and willingness to provide the Sponsor’s representatives access to the hospital 
records, study files, and subject files as they pertain to the study 
 Willingness to participate, including adherence to all study requirements 
 Adequate staff to conduct the study.  
7.2 TRAINING/INITIATION VISIT 
The Sponsor or a representative of the Sponsor will conduct a training session with each 
Investigator and his/her staff to review the Study Protocol,  IFU of the study devices, eCRFs, the 
informed consent process, Ethics Committee (EC) or Institutional Review Board (IRB) 
involvement and guidelines, responsibilities and obligations, reporting requirements, and general 
guidelines for good clinical practices. 
Prior to enrolling subjects at a study site, the following documentation must be provided to the 
Sponsor: 
 EC approval for the Study Protocol  
 EC approval for the Principal Investigator to conduct the study 
 EC and Sponsor approved Informed Consent Form for the study 
 Investigator(s’) curriculum vitae (CV) 
 Signed Investigator Agreement and if applicable, Sub-Investigator Agreement(s)  
 Completed training documentation form (provided by Sponsor or representative) to 
verify the appropriate study staff has been trained accordingly.  
 
8.0 MONITORING PROCEDURES 
 
8.1 MONITORING PROCEDURES 
MCRF as the Sponsor will be responsible for ensuring that adequate monitoring at each site is 
completed to ensure protection of the rights and safety of subjects, and the quality and integrity 
of the data collected and submitted.  Appropriately trained personnel appointed or subcontracted 
by MCRF will conduct monitoring at each site.  The lead coordinator and quality monitor at 
MCRF will be responsible for the monitoring procedure: 
Gail A Shammas, BSN, RN 
Lead Coordinator and Quality Monitor 
Midwest Cardiovascular Research Foundation 
1622 E Lombard Street,  
Davenport, IA 52803 
shammasg@mcrfmd.com 

 
48 
 
Monitoring will be conducted as per MCRF SOP and plan and with monitoring 
documentation per standardized templates  
 Monitors will conduct site visits to ensure accuracy of data, timeliness of data submissions, 
adequate subject enrollment, compliance with applicable laws and regulations, compliance with 
the Study Protocol, compliance with the signed investigator agreement, and compliance with EC 
conditions and guidelines.  Any non-compliance with these items that is not adequately 
addressed by the Principal Investigator/site staff is cause for the Sponsor to put the 
Investigator/site staff on probation or withdraw the Investigator/site staff from the study.  
Frequency of monitoring will be based upon enrollment, study duration, compliance, and any 
suspected inconsistency in data that requires investigation.  
8.2 MONITORING REPORTS 
After each monitoring visit, the monitor will send to the Principal Investigator a letter 
summarizing the monitoring visit.  A monitoring report will be kept on file. The Principal 
Investigator will be responsible for ensuring that follow-up actions needed to resolve issues at 
the site are completed in an accurate and timely manner. 
8.3 FINAL MONITORING VISIT 
Final monitoring visits at the sites will be conducted at the close of the study.  The purpose of the 
final visit is to collect all outstanding study data documents, ensure that the Principal 
Investigator’s files are accurate and complete, review record retention requirements with the 
Principal Investigator, make a final accounting of all investigational devices shipped to the 
Principal Investigator/site, provide for appropriate disposition of any remaining supplies, and 
ensure that all applicable study requirements are met. 
9.0 RESPONSIBILITIES, RECORDS and REPORTS 
 
The proposed study will be performed in accordance with all requirements set forth in the U.S. 
regulations, 21 Code of Federal Regulations (CFR) Parts 50, 54, 56, and 812, the World Medical 
Association Declaration of Helsinki, ISO 14155 (1) and (2), current Good Clinical Practices 
(GCP), International Conference on Harmonization (ICH) and any other applicable local laws 
and regulations. 
 
9.1 RESPONSIBILITIES AND RECORD RETENTION 
The Principal Investigator/site must maintain adequate records on all aspects of the study, 
including the following: 
 Ethics Committee approvals 
 Subject termination information 
 Informed Consent Forms 
 Study Protocol Deviations 
 Case Report Forms 
 Correspondence file regarding study 
 Serious Adverse Events (and 
source documents) 
 
 

 
49 
 
The Principal Investigator/site must maintain the study records for at least two years after 
approval of the device on the market or 7 years after cessation of the study and must contact the 
Sponsor prior to disposal of study records. 
9.2 REPORTS 
Reports that are the Principal Investigator’s responsibility to generate are listed in Table 7.  The 
table also displays information regarding to whom this information is to be sent, and the 
frequency and time constraints around report submission.  If applicable laws, regulations, or EC 
requirements mandate stricter reporting requirements than those listed, the stricter requirements 
must be followed.   
 

 
50 
 
Table 7: Principal Investigator Reporting Responsibilities 
Type of Report 
Principal Investigator Reporting Responsibilities 
Report 
Prepared For 
Reporting Time Frame 
Serious Adverse Events 
or Serious Adverse 
Device Effects  
Sponsor and 
EC 
ASAP, but to Sponsor or representative within 24 hours 
of when Investigator is first aware of the event.  To EC 
according to local guidelines. 
Withdrawal of EC 
approval (or other action 
on the part of the EC that 
affects the study) 
Sponsor 
Within 5 working days of EC decision. 
Progress reports 
Sponsor and 
EC 
At intervals dictated by the EC, but no less than yearly. 
Emergency protocol 
deviations 
Sponsor and 
EC 
ASAP, but to Sponsor no later than 5 working days after 
the deviation occurs.  To EC according to local 
guidelines. 
Use of inappropriate 
Informed Consent Form 
Sponsor and 
EC 
To Sponsor within 5 working days after the deviation 
occurs.  To EC according to local guidelines. 
Final report 
Sponsor and 
EC 
To Sponsor within 3 months after termination or 
completion of study or Investigator’s participation.  To 
EC according to local guidelines. 
Other 
As Required 
Upon request by the EC to provide accurate, complete, 
and current information about any aspect of the study.  
 
9.3 
 RECORDS CUSTODY 
An Investigator may withdraw from the study.  If the Principal Investigator withdraws from the 
study, responsibility for follow-up and maintaining the records must be transferred to a 
responsible party (such as another study Investigator).  Notice of transfer must be provided in 
writing by the Principal Investigator to the Sponsor and the EC no later than 10 working days 
after transfer occurs. 
9.4 IRB APPROVALS 
IRB written approval will be obtained before being allowed to conduct and participate in the 
study. This approval letter must identify the study name, approved protocol number (including 
revision number), the date of the approval as well as the expiration date of such an approval.  
The investigator is responsible for fulfilling any conditions of approval imposed by the IRB, 
such as regular reporting, study timing, and for maintaining continuation of the approval during 
the entire study period.  The investigator must also keep on file all correspondence with the IRB 
and forward copies of such correspondence to MCRF.  
9.5 INFORMED CONSENT 
MCRF will provide a template ICF for IRB submission prior to the site initiation.  This 
template may be modified to suit the requirements of the individual study site.   

 
51 
 
A copy of the ICF must be given to each subject enrolled in the study.  The investigator or 
assigned designee must administer this approved ICF to each prospective study subject, and 
obtain the subject's signature or a legally approved designee’s signature along with the date of 
consent prior to enrollment in the study.  The ICF must be obtained in accordance with the 
applicable guidelines on 21 CFR Part 50, current GCP, the Declaration of Helsinki,  ISO 
14155 (1) and (2), or local regulations and laws, whichever represents the greater protection 
of the individual.  The subjects must be informed about their right to withdraw from the study 
at any time and for any reason without sanction, penalty, or loss of benefits to which the 
subject is otherwise entitled and also informed that withdrawal from the study will not 
jeopardize their future medical care.  The institutional standard subject consent form does not 
replace the study ICF. 
9.6 INFORMED CONSENT (ICF) 
All information and data sent to MCRF concerning subjects or their participation in this 
study will be considered confidential.  All data used in the analysis and reporting of this 
evaluation will be used in a manner without identifiable reference to the subject.  The 
investigator consents to audits by the staff of MCRF and its authorized local governmental body 
to review the study subjects’ medical records, including any test or laboratory data that might 
have been recorded on diagnostic test media. 
9.7 AMENDING THE PROTOCOL 
The protocol can be amended only by the Sponsor. All changes must be submitted to the 
IRB for review and approval. Any change that would require alteration of the ICF must receive 
approval from the IRB prior to implementation.  Following approval, the protocol amendment 
will be distributed to all protocol recipients at the study sites.  
9.8 PROTOCOL DEVIATIONS 
A Protocol Deviation CRF must be completed for each study protocol deviation (e.g., failure 
to obtain informed consent, enrolling a subject who does not meet inclusion/exclusion criteria, 
not performing required testing, missed follow-up visits, etc.).  Investigators must notify the 
reviewing IRB of any deviation from the Study Protocol that was done to protect the life or 
physical well-being of a subject (medical emergencies).  Such notice should be given within 48 
hours where feasible but no later than 5 days after occurrence.  
9.9 CASE REPORTS FORMS (CRF) 
CRFs for individual subjects will be developed by MCRF or subcontracted by MCRF to a 
qualified CRO. CRFs are used to record study data and are an integral part of the study and 
subsequent reports.  After the data have been submitted, corrections will be initiated via queries 
to be completed by study site personnel to investigator.  CRFs and queries must be signed by the 
investigator 
 
10.0 DATA and QUALITY MANAGEMENT 
 

 
52 
 
A full-featured relational database will be on a secure central server that is backed up regularly. 
The server will be accessible by password for all approved users via the internet, and data 
analytical workstations will be used for data processing and management.  Conventional data 
verification sub-routines will be extensively programmed to test entry and logical errors, while 
all individual (subject-based) eCRFs will be linked for cross-reference.  Periodic analysis of each 
data field (across subjects) will be performed in order to examine the expected distributions of 
data, and to identify outliers for possible data mistakes.  Corrections to data mistakes will be 
requested via queries.  Each completed query response must be verified by the Investigator (or 
designee) and submitted.  
All information and data concerning subjects or their participation in this study will be 
considered confidential.  Only authorized personnel will have access to these confidential files.  
All data used in the analysis and reporting of this evaluation will be without identifiable 
reference to the subject. 
11.0 PUBLICATION STRATEGY 
 
 
At the conclusion of all 1-year follow-up visits, a multi-site abstract reporting the preliminary 
results may be prepared and presented at one or more major endovascular meetings by Dr 
Nicolas Shammas.  A multi-site publication may also be prepared for print in a peer-reviewed 
scientific journal at the conclusion of the study. Following the national PIs (Shammas and 
Banerjee), additional co-authors will be added to the main manuscript by order of number of 
patients enrolled in the study. Final number of coauthors will be determined based on patient 
enrolment, quality of data and lack of significant protocol violation. Investigators with 
significant protocol deviations that jeopardize data quality may not be considered as authors. The 
final decision for co-authorship will be determined by the Sponsor.  
The publication of results from any single-site experience within the study must not be submitted 
for publication (by itself or as part of other registries) until approval from the Sponsor is granted 
and after the publication of the main manuscript.  A proposal for a publication will be sent to the 
Sponsor for review and approval. MCRF will review and approve all publications for 
presentation at any meeting or for publications in journals or magazines. A significant 
contribution by each author is expected for authorship. The national PIs are expected to review, 
approve and co-author any additional publications prior to submission to Journals or other 
publications media resulting from this study.  

 
53 
 
 
12.0 DEFINITIONS 
 
 
Abrupt Closure: Vessel occlusion at the site of treatment within 24 hours after successful index 
procedure. 
Access Site Complications: Adverse sequelae at the access site as a result from cathether-based 
interventions, including arterio-venous fistula, bleeding, hematoma, infection and 
pseudoaneurysm.  
Adjunctive Treatment: A procedure performed after treatment with the protocol-defined 
treatment (JS + PTA) to treat major flow limiting dissection (grade D or greater), perforations, 
occlusive complications (i.e. recoil) or residual stenosis greater than 30% in the target lesion.  
Adverse Event:  Any untoward and unintended clinical sign, symptom, or disease in a subject.  
This definition does not imply that there is a relationship between the adverse event and the 
device under investigation. 
Adverse Event Definitions:  Reportable Events 
Serious Adverse 
Event (SAE) 
Serious Adverse Event:  Any adverse events that led to a death or led 
to a serious deterioration in the health of the subject that 1) resulted in a 
life-threatening illness or injury, 2) resulted in a permanent impairment 
of a body structure or a body function, 3) required inpatient 
hospitalization or prolongation of existing hospitalization, or 4) resulted 
in medical or surgical intervention to prevent permanent impairment to a 
body structure or body function.  This definition also includes any 
adverse event that led to fetal distress, fetal death or a congenital 
abnormality or birth defect.   
Major Adverse 
Events 
Major Adverse Events (MAE) as individual endpoints in-hospital 
and up to 30 days :  Include device-induced vascular injury as reported 
by the operator, amputation (major and minor unplanned), death, 
significant distal embolization requiring the use of pharmacologic or 
mechanical means to treat (other than a vasodilator), perforation 
(extravasation of blood outside the vessel wall), major bleeding, non-
fatal myocardial infarction (defined as the occurrence of more than 20 
minutes of chest pain post procedure with an increase in troponin), 
stroke, access complications (AV fistula and pseudoaneurysm), bail out 
stenting, acute renal failure (drop in crcl by > 25% from baseline), acute 
(< 24 hours) or subacute (< 1 month , > than 24 hours) vessel closure. 
Major Adverse Events (MAE) as composite endpoint at 30 days: 
unplanned amputation (major or minor), death or TLR at 30 days (TLR 
includes bail out stenting) 
Major Adverse Event Rate as individual and composite endpoint at 

 
54 
 
6 months and 1 Year: Defined as major unplanned amputation of the 
treated limb, death or TLR at 6 months and 1 year (bail out stent in the 
Lab is included as TLR) 
UADE 
Unanticipated or Unexpected Adverse Device Effects:  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 protocol or application (including a supplementary plan 
or application), or any other unanticipated serious problem associated 
with a device that relates to the rights, safety, or welfare of subjects. 
 
 
Adverse Event Relationship Categories: 
Related:  AE that has a strong temporal relationship to the study procedure, a study 
requirement, or the presence or performance of the investigational device/system or drug 
and an alternative etiology is highly unlikely. 
Possibly Related:  AE that has a temporal relationship to the study procedure, a study 
requirement, or the presence or performance of the investigational device/system or drug 
and an alternative etiology is unlikely. 
Not Related:  AE is due to the underlying disease state or concomitant medication or 
therapy, and was not caused by the study procedure, a study requirement, or the 
investigational device/system or drug. 
Not Assessable:  It is not possible to assess whether or not the adverse event is related to 
the study procedure, a study requirement, or the investigational device/system or drug. 
Amputation: 
Major Unplanned Amputation:  Surgical removal of a limb or a part of a limb above the 
metatarsal line where prosthesis is required for standing or walking, that was unanticipated 
prior to the index procedure. 
Minor Amputation: Surgical removal of toes at or below metatarsus preserving 
functionality of foot.  
Aneurysm: A localized, pathological, blood-filled dilatation of a blood vessel caused by a 
weakening of the vessel wall. 
Ankle-Brachial Index (ABI): The ratio of the highest ankle systolic pressure to the highest 
brachial systolic pressure. 
Artery Dissection: Intimal disruption of the vessel wall with or without medial or adventitial 
contrast staining.  See also National Heart, Lung and Blood Institute (NHLBI) Classification 
of Dissection. 
Artery Perforation:  Identifiable by extravasation of contrast media outside the arterial 
adventitial space. 

 
55 
 
Artery Rupture:  Large transmural disruption of a vessel with gross extravasation and 
hemorrhage. 
Arterio-venous (AV) Fistula:  A communication between an artery and a vein in which the 
arterial blood flows directly into a neighboring vein. 
Bleeding:  Blood loss resulting from the percutaneous interventional procedure or adjunctive 
drug therapy that may require transfusion of blood products. 
Chronic Renal Insufficiency:  Dialysis dependent, or eGFR < 30 ml/min or creatinine >2.5. 
Clinically Significant Distal Embolism: A clinically relevant obstruction of a blood vessel by a 
foreign substance (plaque or debris) or a blood clot that requires further mechanical or 
pharmacologic treatment besides vasodilators.  Clinical relevance is determined either by a 
surgical or medical intervention and/or the presence of symptoms (i.e. decreased ABI, 
symptomatic claudication, etc). 
Compressible Artery:  An artery without significant calcification that can be evaluated by 
duplex ultrasound or an artery that results in an ABI value < 1.3.  
Death: The termination of life. 
Device Outcome:  Categorized by < 50% residual stenosis following JS atherectomy alone and 
without additional adjunctive PTA or bail out procedures as determined by the Angiographic 
Core Laboratory. 
Diabetes (History of):  Defined as patients who have been diagnosed with either Type I or Type 
II diabetes and are currently taking oral hypoglycemics or insulin or have a hemoglobin A1C > 
7%. 
Discharge:  The time point when the subject is released from the admitting hospital, transferred 
to another facility, or has expired. 
Distal Embolization:  Migration of air, plaque, thrombus, or debris that occludes the distal 
target vessel or one of its branches. 
Embolism:  Obstruction of a blood vessel by a foreign substance (air, plaque, debris) or a blood 
clot. 
Emergent Surgical Revascularization: Surgery performed on an urgent or emergent basis as a 
result of the PTA procedure and/or use of a study device.  
Enrollment: The subject is enrolled in the study after he/she has signed the patient informed 
consent and has been determined to meet all inclusion and none of the exclusion criteria.  The 
point of enrollment is defined as the moment an exchangeable guidewire and treatment catheter 
cross the target lesion in the true lumen.   
Fever:  An increase in internal body temperature to levels that are above normal (37°C, 98.6°F). 
Gastrointestinal (GI) bleeding:  any bleeding that starts in the gastrointestinal tract, which may 
extend from the mouth to the anus. 
Hematoma:  Localized mass of extravasated blood ≥ 5 cm that prolongs hospitalization. 
Hemorrhage:  Bleeding requiring hospitalization, repeat procedure, operation or transfusion. 

 
56 
 
Hypertension: Increase in systolic blood pressure above 140 mm Hg or a diastolic blood 
pressure above 90 mm Hg. 
Hypotension: Fall in systolic blood pressure that requires intravenous treatment with 
vasopressors or inotropic agents. 
Index Procedure: The procedure in which the subject has the study procedure performed or 
attempted. 
Index Lesion: The target lesion treated during the index procedure 
Infection:  Inflammation caused by bacterial or viral sources, such as, urinary tract infection, 
puncture site infection, sepsis, endocarditis, and bacteremia from IV site.   
Inflammation: An immunologic response to infection or trauma that can result in localized 
redness, swelling, heat, pain and dysfunction of the organs involved. 
Inflow Tract:  Vascular access point to the area of the target lesion. 
Intraluminal thrombus: A blood clot within a vessel. 
Intimal Flap:  Superficial dissection of the vessel that does not result in medial or adventitial 
contrast staining (NHLBI Type A dissection). 
Invasive Assessment/Procedure:  Any assessment, intervention or therapy that penetrates the 
skin, excluding administration of parenteral fluids or drugs. 
Ischemia: a restriction in arterial blood flow by stenosis, restenosis or occlusion that, if 
prolonged, can lead to tissue damage.  
JS pass: Movement of the JS across the target area. One pass is the movement of the JS from the 
proximal to the distal end of the lesion 
Major bleed by TIMI criteria: Loss of more than 5 gm/dl of Hemoglobin or the need to 
transfuse 5 Units of blood or intracranial bleed 
Minor Bleed by TIMI criteria: a bleed other than non TIMI major bleed 
Myocardial Infarction (Non-Q wave):  Post-treatment elevation of CK-MB more than 3 
times the upper limit of lab normal value without evidence of pathologic Q-waves present on 
EKG.  Elevated serum troponin levels are not sufficiently validated to be considered sole 
evidence of an MI in the absence of CK-MB elevations. 
Myocardial Infarction (Q wave):  Development/appearance of new pathological Q-waves 
in more than 2 contiguous leads per 12-lead electrocardiogram (EKG/ECG). 
National Heart, Lung and Blood Institute (NHLBI) Classification of Dissection:30 
Dissection 
Description 
Type A 
Small radiolucent area within the lumen of the vessel disappearing with 
the passage of contrast material 
Type B 
Appearance of contrast medium parallel to the lumen of the vessel 
disappearing within a few cardiac cycles 
Type C 
Dissection protruding outside the lumen of the vessel persisting after 
passage of the contrast material 
 
Type D 
Spiral shaped filling defect with delayed runoff of the contrast material 

 
57 
 
Dissection 
Description 
in the distal vessel 
Type E 
Persistent luminal filling defect with delayed runoff of the contrast 
material in the distal vessel 
Type F 
Filling defect accompanied by total coronary occlusion 
 
Net Lumen: The difference between the target lesion minimum lumen diameter at baseline and 
at follow-up per angiographic assessment. 
Occlusion:  An obstruction within an artery. 
Patency Classifications: 
 Patency via Duplex (Peak Systolic Velocity ≤ 2.5):  Defined by duplex 
ultrasound measurement of peak systolic velocity (PSV) ratio ≤ 2.5 at the target 
lesion. 
 Patency via angiography: Defined as < 50% stenosis per angiography as 
determined by the Angiographic Core Laboratory. 
 Assisted primary Patency:  Defined as < 50% stenosis per angiography or 
duplex as maintained by repeat percutaneous intervention of a non-occluded 
vessel 
 Secondary Patency: Defined as < 50% stenosis per angiography or duplex, as 
maintained by repeat percutaneous intervention of a non-occluded or occluded 
vessel 
 
 
Percent Stenosis:  Native vessel diameter as measured at the most narrow point of the lesion 
divided by the estimated native vessel diameter (the mean of the vessel diameters proximal and 
distal to the lesion) at that location.   
   % Stenosis = 



2
/
)
(
diameter
vessel
distal
diameter
vessel
proximal
mm
lesion
of
segment
narrow
most
at
Diameter

  
Physician-Directed Subject Withdrawal:  Withdrawal of a subject from the study at the 
direction of the Principal Investigator.  Reasons for physician-directed subject withdrawal 
include, but are not exclusive to: the subject is not adhering to the Study Protocol requirements, 
the subject has enrolled in another study that conflicts with the JET-ISR outcomes of interest, or 
the physician deems it in the best interest for the safety or welfare of the subject to withdraw. 
Pre-Procedure:  The time until the procedure begins (before arterial access is obtained). 
Principal Investigator:  Physician responsible for overall clinical management of subjects 
enrolled at his/her institution. Assumes overall responsibility and accountability for the clinical 
team and for data obtained from each subject participating in the study. Ensures compliance with 
the Study Protocol, applicable laws, and applicable regulations; ensures informed consents are 
signed, and reviews and signs eCRF indicating documents are accurate and complete. 
Procedural Outcome: Categorized by < 30% residual stenosis following the protocol-defined 
treatment (JS + PTA) with provisional or bail out procedures as determined by the Angiographic 
Core Laboratory. 

 
58 
 
Procedural Success: Defined as ≤30% residual diameter stenosis following JS + PTA without 
provisional or bailout procedures. 
Protocol Deviation:  Any divergence from the Study Protocol. 
Pseudoaneurysm: Perforation of the vessel with arterial blood flow outside of the vessel.  
Renal Failure:  Failure of the kidneys to perform essential functions that requires dialysis. 
Runoff Vessel:  An artery distal to treated vessel, including the popliteal, peroneal tibials and the 
dorsalis pedis.  
Rutherford Clinical Category31:  A classification system of clinical categories of chronic limb 
ischemia ranging from 0 to 6.  The categories and clinical descriptions are:   
Category 
Clinical Description 
0 
Asymptomatic--no hemodynamically significant occlusive disease 
1 
Mild claudication 
2 
Moderate claudication 
3 
Severe claudication 
4* 
Ischemic rest pain 
5* 
Minor tissue loss—non-healing ulcer, focal gangrene with diffuse pedal ischemia 
6* 
Major tissue loss--extending above TM level, functional foot no longer salvageable 
      *Categories 4, 5, and 6 are embraced by the term chronic critical ischemia.†Five minutes at 2 mph on a 12% incline. 
 
Sepsis:  Systemic inflammatory response to infection. 
Severe or Moderate Calcification:  Grade 2 (moderate) or higher (severe) as defined by the 
Peripheral Arterial Calcium Scoring System (PACSS)32 
 
 
Stenosis:  An abnormal narrowing of an artery. 
Stroke:  Neurological dysfunction caused by a brain disturbance or ischemia, with clinical 
symptoms lasting >24 hours or imaging of an acute clinically relevant brain lesion in patients 
with rapidly vanishing symptoms. 

 
59 
 
Study Coordinator:  Employee at study site who assists Principal Investigator with study 
activities as delegated by the Principal Investigator, including tracking subjects involved in the 
study, scheduling testing and follow-up visits, maintaining study records, completing and 
providing eCRFs to the Sponsor in a timely manner. 
Sub-acute Closure:  Vessel occlusion at the site of treatment between 24 hours and 4 
weeks after successful index procedure. 
Sub-Investigator(s): Physician(s) responsible for study activities in coordination with 
Principal Investigator and in accordance to the Study Protocol.   
Systemic Infection: the bloodstream infection that affects a number of organs and/or 
tissues, or affects the body as a whole. 
Target Lesion:  The lesion meeting all of the angiographic inclusion criteria and none of 
the exclusion criteria is the target lesion. Only one target lesion is allowed per subject.  
Target Lesion Revascularization (TLR) at 6 months: TLR is defined as retreatment of the 
index lesion (extended 1 cm proximal and distal to the lesion) at 6 months. For the primary 
endpoint, intra-procedural bail out stenting of the index lesion is considered meeting a TLR 
endpoint. (ITT analysis).  
Target Lesion Revascularization (TLR) at 6 months: TLR is defined as retreatment of the 
index lesion (extended 1 cm proximal and distal to the lesion) at 6 months. For the secondary 
endpoint, Intra-procedural bail out stenting of the index lesion is NOT considered meeting a TLR 
endpoint. (ITT analysis) 
Target Lesion Revascularization (TLR) at 1 year: TLR is defined as retreatment of the index 
lesion (extended 1 cm proximal and distal to the lesion) at 1 year 
                                ITT (bail out stent in the Lab is considered as TLR)  
                      ITT (bail out stent in the Lab is not considered as TLR) 
Target Lesion Patency at 6 months and 1 year: Defined as PSVR ≤ 2.5 at the treated site or < 
50% stenosis by angiography as determined by the Angiographic Core Laboratory in the absence 
of TLR, amputation, and/or surgical bypass (the evaluation of patency is extended to one cm 
proximal and one cm distal to the target lesion) 
Clinically Driven Target Lesion Revascularization at 6 months and 1 year: Defined as any 
re-intervention or artery bypass graft surgery involving the target lesion in which the subject has 
a ≥ 70% diameter stenosis (Peak Systolic Velocity Ratio (PSVR) > 3.5 may substitute if a pre-
intervention angiogram has not been recorded) and at least two of the following:  worsening 
RCC by one category, worsening WIQ score by ≥20 points, or an ABI drop > 0.15 from 
baseline. 
                      ITT (bail out stent in the Lab is considered as TLR)  
                      ITT (bail out stent in the Lab is not considered as TLR)  
 
Target Vessel Failure at 6 months and 1 year: Defined as major unplanned amputation related 
to the treated limb, vascular mortality related to treated limb and target vessel revascularization 
at 6 months  and 1 year (stenting in the lab is not considered a TLR/TVR) 

 
60 
 
Target Lesion failure at 6 months and 1 year: Defined as major unplanned amputation related 
of the treated limb, vascular mortality related to treated limb and target lesion revascularization 
at 6 months and 1 year (stenting in the lab is not considered a TLR) 
TASC: See Trans-Atlantic Inter-Society Consensus II 
Thrombosis:  The formation or development of thrombus inside a blood vessel, 
obstructing the flow of blood.  
Thrombus: A blood clot within a vessel, which obstructs the flow of blood. 
Total Occlusion: 100% stenosis within an artery. 
Trans-Atlantic Inter-Society Consensus II (TASC II)29: A classification scheme for the 
assessment and management of peripheral arterial disease published in 2007.   
 
Femoropopliteal 
TASC II 
classification**33 
Type A.  
Single stenosis ≤10 cm in length 
Single occlusion ≤5 cm in length 
Type B. 
Multiple lesions (stenoses or occlusions), each ≤5 cm 
Single stenosis or occlusion ≤15 cm not involving the 
infrageniculate popliteal artery 
Single or multiple lesions in the absence of continuous tibial 
vessels to improve inflow for a distal bypass 
Heavily calcified occlusion ≤5 cm in length 
Single popliteal stenosis 
Type C 
Multiple stenoses or occlusions totaling >15 cm with or without 
heavy calcification 
Recurrent stenoses or occlusions that need treatment after two 
endovascular interventions 
Type D 
Chronic total occlusions of CFA or SFA (>20 cm, involving the 
popliteal artery) 
Chronic total occlusion of popliteal artery and proximal 
trifurcation vessels 
 
** Eur J Vasc Endovasc Surg 33, S1eS70 (2007) 
http://www.sirweb.org/clinical/cpg/TASC_guidelines.pdf 
 
 
Transient Ischemic Attack (TIA):  Brief episode of neurological dysfunction caused by a focal 
disturbance of brain or retinal ischemia, with clinical symptoms typically lasting less than 1 hour, 
and without evidence of infarction. 

 
61 
 
Treatment interval: Time from JS activation until deactivation (via physician’s hand control).  
Unanticipated or Unexpected 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 protocol or application (including a supplementary plan or 
application), or any other unanticipated serious problem associated with a device that 
relates to the rights, safety, or welfare of subjects. 
Vessel Spasm: A sudden, brief tightening of a blood vessel. 
 
. 

 
62 
 
13.0  REFERENCES 
 
 
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JETSTREAM System. J Invasive Cardiol. 2013;25 (Supplement B):2B-15B. 
2. Shammas NW. JETSTREAM atherectomy: a review of technique, tips, and tricks in 
treating the femoropopliteal lesions. Int J Angiol. 2014. DOI: 10.1055/s-0034-1390083 
2b. Criqui M, Vargas V, Denenberg J et al. Ethnicity and peripheral arterial disease. The
 
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3. Schillinger M, Sabeti S, Loewe C, et al. Balloon angioplasty versus implantation of 
nitinol stents in the superficial femoral artery. N Engl J Med 2006;354:1879-88. 
4. Laird JR, Katzen BT, Scheinert D, et al. Nitinol stent implantation versus balloon 
angioplasty for lesions in the superficial femoral artery and proximal popliteal artery: 
twelve-month results from the RESILIENT randomized trial. Circ Cardiovasc Interv 
2010;3:267-76. 
5. Schillinger M, Sabeti S, Dick P, et al. Sustained benefit at 2 years of primary 
femoropopliteal stenting compared with balloon angioplasty with optional stenting. 
Circulation 2007;115:2745-9. 
6. Laird JR, Katzen BT, Scheinert D, et al; RESILIENT Investigators. Nitinol stent 
implantation vs. balloon angioplasty for lesions in the superficial femoral and proximal 
popliteal arteries of patients with claudication: three-year follow-up from the 
RESILIENT randomized trial. J Endovasc Ther. 2012;19:1-9. 
7. Iida O, Nanto S, Uematsu M, et al. Influence of stent fracture on the long-term patency 
in the femoro-popliteal artery: experience of 4 years. JACC Cardiovasc Interv. 
2009;2:665-71. 
8. Laird JR. Limitations of percutaneous transluminal angioplasty and stenting for the 
treatment of disease of the superficial femoral and popliteal arteries. J Endovasc Ther. 
2006;13 Suppl 2:II30-40. 
9. Shammas NW. Restenosis after lower extremity interventions. J Endovasc Ther 2009; 
16 (Suppl I):I170-I182 
10. Shammas NW, Shammas GA, Helou TJ, et al. Safety and 1-year revascularization 
outcome of SilverHawk atherectomy in treating in-stent restenosis of femoropopliteal 
arteries: A retrospective review from a single center. Cardiovasc Revasc Med. 2012 
May 8. [Epub ahead of print] 
11. Sixt S, Rastan A, Beschorner U, et al. Acute and long-term outcome of Silverhawk 
assisted atherectomy for femoro-popliteal lesions according the TASC II classification: 
a single-center experience. Vasa. 2010;39(3):229-36. 
12. Zeller T, Rastan A, Sixt S, et al. Long-term results after directional atherectomy of 
femoro-popliteal lesions. J Am Coll Cardiol. 2006;48:1573-8.  
13. Dick P, Sabeti S, Mlekush W et al. Conventional Balloon Angioplasty versus 
Peripheral Cutting Balloon Angioplasty for Treatment of Femoropopliteal Artery In-
Stent Restenosis: Initial Experience. Radiology 2008; 248, 297-302. 
14. Banerjee S, Das T, Dippel EJ, et al. Cryoplasty Versus Conventional Balloon 
Postdilation of Nitinol Stents for Peripheral Arterial Interventions (COBRA Trial). 
JACC 2011; Supp, TCT-2011. Presented at Transcatheter Cardiovascular Therapeutics, 

 
63 
 
November 11, 2011, San Francisco, CA, USA as Late Breaking Trials and First Report 
Investigations session. 
15. Dake MD, Scheinert D, Tepe G, et al; Zilver PTX Single-Arm Study Investigators. 
Nitinol stents with polymer-free paclitaxel coating for lesions in the superficial femoral 
and popliteal arteries above the knee: twelve-month safety and effectiveness results 
from the Zilver PTX single-arm clinical study. J Endovasc Ther. 2011;18:613-23 
16. Stabile E, Virga V, Salemme Let al. Drug-eluting balloon for treatment of superficial 
femoral artery in-stent restenosis. J Am Coll Cardiol. 2012;60:1739-42 
17. Zeller T, Dake MD, Tepe G, et al. Treatment of femoropopliteal in-stent restenosis with 
paclitaxel-eluting stents. JACC Cardiovasc Interv. 2013;6:274-81. 
18. Dippel EJ, Makam P, Kovach R, et al. Randomized controlled study of excimer laser 
atherectomy for treatment of femoropopliteal in-stent restenosis: initial results from the 
EXCITE ISR trial (EXCImer Laser Randomized Controlled Study for Treatment of 
FemoropopliTEal In-Stent Restenosis). JACC Cardiovasc Interv. 2015;8(1 Pt A):92-
101 
19. Bosiers M, Deloose K, Callaert J, et al. Superiority of stent-grafts for in-stent restenosis 
in the superficial femoral artery: twelve-month results from a multicenter randomized 
trial. J Endovasc Ther. 2015;22:1-10 
20. Shammas NW,  Shammas GA,  Park H, Banerjee S, Mohammad A, Jerin M.  Safety 
and in-Hospital Outcomes of JetStream Atherectomy in Treating In-Stent Restenosis of 
Femoropopliteal Arteries. Presented at American College of Cardiology Scientific 
Sessions, San Diego, CA, March 2015. JACC 2015;65(10S): A1812 
21. Silingardi R, Cataldi V, Moratto R, et al. Mechanical thrombectomy in in-stent 
restenosis: preliminary experience at the iliac and femoropopliteal arteries with the 
Rotarex System. J Cardiovasc Surg (Torino). 2010; 51(4):543-50. 
22. Wissgott C, Kamusella P, Andresen R. Treatment of in-stent reocclusions of 
femoropopliteal arteries with mechanical rotational catheters. Rofo. 2011;183:939-44.  
23. Laird JR Jr, Yeo KK, Rocha-Singh K, et al. Excimer laser with adjunctive balloon 
angioplasty and heparin-coated self-expanding stent grafts for the treatment of 
femoropopliteal artery in-stent restenosis: Twelve-Month Results From the SALVAGE 
Study. Catheter Cardiovasc Interv. 2012 Mar 15. doi: 10.1002/ccd.23475. [Epub ahead 
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24. Liistro F, Angioli P, Porto I, et al. Paclitaxel-eluting balloon vs. standard angioplasty to 
reduce recurrent restenosis in diabetic patients with in-stent restenosis of the superficial 
femoral and proximal popliteal arteries: the DEBATE-ISR study. J Endovasc Ther. 
2014;21:1-8 
25. van den Berg JC, Pedrotti M, Canevascini R, et al. In-stent restenosis: mid-term results 
of debulking using excimer laser and drug-eluting balloons: sustained benefit? J 
Invasive Cardiol. 2014;26:333-7. 
26. Sixt S, Carpio Cancino OG, Treszl A, et al. Drug-coated balloon angioplasty after 
directional atherectomy improves outcome in restenotic femoropopliteal arteries. J 
Vasc Surg. 2013;58:682-6. 
27. Shammas NW et al. Final results of the JetStream ISR results.  Presented NCVH 2015, 
New Orleans, LA (Manuscript submitted for publication) 
28. Shammas NW, Sarode K, Mohammad A, Master R, Shammas AN, Ali MI, Gigliotti 
OS, Armstrong EJ, Brilakis ES, Banerjee S. Indications for use and outcomes with the 
Jetstream atherectomy device from the XLPAD registry. Presented at SCAI 2015, San 

 
64 
 
Diego May 6-9, 2015. Catheterization and Cardiovascular Interventions 2015. 
Abstracts 082, S51 
29. Shammas NW, Aasen N, Bailey L, et al. Two Blades-Up Runs Using the JetStream 
Navitus Atherectomy Device Achieve Optimal Tissue Debulking of Nonocclusive In-
Stent Restenosis: Observations From a Porcine Stent/Balloon Injury Model. J Endovasc 
Ther. 2015 Jun 24. pii: 1526602815592135. [Epub ahead of print] 
30. Huber MS, Mooney JF, Madison J, Mooney MR.  Use of a morphologic classification 
to predict clinical outcome after dissection from coronary angioplasty.  Am J Cardiol 
1991; 68: 467-71. 
31. Rutherford RB, Baker JD, Ernst C, Johnston KW, Porter JM, Ahn S, Jones DN. 
Recommended standards for reports dealing with lower extremity ischemia: revised 
version. J Vasc Surg. 1997 Sep;26(3):517-38 
32. Rocha-Singh KJ, Zeller T, Jaff MR. Peripheral arterial calcification: prevalence, 
mechanism, detection, and clinical implications. Catheter Cardiovasc Interv. 2014 May 
1;83(6):E212-20. doi: 10.1002/ccd.25387. Epub 2014 Feb 10. 
33. Norgren L, Hiatt WR, Dormandy JA, et al. Inter-Society Consensus for the 
Management of Peripheral Arterial Disease (TASC II). Eur J Vasc Endovasc Surg. 
2007;33 Suppl 1:S1-75. 
34. Krankenberg H, Tubler T, Ingwersen M. Drug-Coated Balloon Versus Standard 
Balloon for Superficial Femoral Artery In-Stent Restenosis: The Randomized Femoral 
Artery In-Stent Restenosis (FAIR) Trial. Circulation. 2015 Dec 8;132(23):2230-6 
35. Beschorner U, Krankenberg H, Scheinert D, Sievert H, Tübler T, Sixt S, Noory E, 
Rastan A, Macharzina R, Zeller T. Rotational and aspiration atherectomy for 
infrainguinal in-stent restenosis. Vasa. 2013 Mar;42(2):127-33. doi: 10.1024/0301-
1526/a000256. 
36. Shammas NW, Shammas GA, Aasen N, Jarvis G. Number of Blades-up Runs Using 
JetStream XC Atherectomy for Optimal Tissue Debulking in Patients with 
Femoropopliteal Artery In-Stent Restenosis. J Vasc Interv Radiol. 2015 
Dec;26(12):1847-51. doi: 10.1016/j.jvir.2015.08.026. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
65 
 
Appendix A 
JET ISR 
 
 
Meta-analysis 
 
We completed a meta-analysis for the 3 randomized trials published (1-3) with femoropopliteal 
in-stent restenosis where the control arm was balloon angioplasty alone. Below is a table of this 
meta-analysis. This showed that TLR with balloon angioplasty alone was 37.9%.  
 
Estimated Counts of TLR with Bailout Stenting at 6-Months 
Estimated Counts of TLR with Bailout Stenting at 6-Months 
Author, year 
Treatment 
Control 
Total 
Boisers et al., 2015 
(2/39) 5.3% 
(15/44) 34.2% 
(17/83) 20.5% 
Krankenberg et al., 2015 
(3/62) 5.2% 
(15/57) 26.0% 
(18/119) 15.1% 
Dipple et al., 2015 
(45/169) 26.5% 
(39/81) 48.2% 
(84/250) 33.6% 
Total 
(50/270) 18.5% 
(69/182) 37.9% 
(119/452) 26.3% 
 
Meta-Analysis for Estimated TLR with Bailout Stenting at 6-Months 
Estimated TLR with Bailout Stenting at 6-Months 
 
 
Author, year 
n 
Weight 
Treatment 
Control 
Risk Difference 
Risk Ratio 
Odds Ratio 
Boisers et al., 2015 
83 
18.4% 
5.3% 
34.2% 
-28.9% [-44.6%, -13.2%] 
0.15 [0.04, 0.62] 
0.10 [0.02, 0.47] 
Krankenberg et al., 2015 
119 
26.3% 
5.2% 
26.0% 
-20.8% [-33.5%, -8.1%] 
0.20 [0.06, 0.65] 
0.14 [0.03, 0.57] 
Dipple et al., 2015 
250 
55.3% 
26.5% 
48.2% 
-21.7% [-34.5%, -8.9%] 
0.55 [0.39, 0.77] 
0.39 [0.22, 0.68] 
Total 
452 
100.0% 
18.5% 
37.9% 
-19.4% [-27.8%, -11.0%] 
0.49 [0.36, 0.67] 
0.37 [0.24, 0.57] 
 
The Breslow- Day test indicates that TLR with Bailout has no heterogeneity and thus can be 
combined into a meta-statistic (p-value=0.1764) (Figure below).   
 
 
 
 

 
66 
 
New Statistical analysis for Jet-ISR 
 
TLR with bailout stenting from historic control from meta-analysis:  
37.9% 
TLR with bailout stenting from Jetstream ISR feasibility study: 
 
20.7% 
(2 bailout stent for suboptimal results + 4 TLR at 6 months/29 limbs) 
Power 80% 
Alpha 0.025 
 
If one assumes a 1:1 ratio of actual treatment:control (instead of the original 2:1) 
 
We are planning a study of independent cases and controls with 1 control(s) per case.  
Prior data indicate that the failure rate among controls is 0.38.  If the true failure rate for 
experimental subjects is 0.21, we will need to study 112 experimental subjects and 112 control 
subjects to be able to reject the null hypothesis that the failure rates for experimental and control 
subjects are equal with probability (power) 0.8 (meta-analysis provides 182 controls which is 
more than needed for this analysis).   The Type I error probability associated with this test of this 
null hypothesis is 0.05.  We will use an uncorrected chi-squared statistic to evaluate this null 
hypothesis. Assumingly a loss of 20% of patients on follow-up a minimum of 134 patients will 
be enrolled.  
 
References 
 
1. Dippel EJ, Makam P, Kovach R, et al. Randomized controlled study of excimer laser 
atherectomy for treatment of femoropopliteal in-stent restenosis: initial results from 
the EXCITE ISR trial (EXCImer Laser Randomized Controlled Study for Treatment 
of FemoropopliTEal In-Stent Restenosis). JACC Cardiovasc Interv. 2015;8(1 Pt 
A):92-101 
2. Bosiers M, Deloose K, Callaert J, et al. Superiority of stent-grafts for in-stent 
restenosis in the superficial femoral artery: twelve-month results from a multicenter 
randomized trial. J Endovasc Ther. 2015;22:1-10 
3. Krankenberg H, Tu ̈bler T, Ingwersen M, et al. Drug-Coated Versus Standard Balloon 
for Superficial Femoral Artery In-Stent Restenosis:  The Randomized Femoral Artery 
In-Stent Restenosis (FAIR) Trial, CIRCULATIONAHA 2015; 115.017364. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

 
67 
 
Study Protocol MCRF-S-002-2015 
 
JET-ISR Trial 
 
JetStream Atherectomy for the Treatment of In-stent 
Restenosis of the Femoropopliteal Artery 
Version 2 
Amendment 1 
September 11, 2016 
 
Sponsor 
Midwest Cardiovascular Research Foundation 
 
National Principal Investigators 
Nicolas W Shammas, MD, MS, FACC, FSCAI 
Subhash Banerjee, MD, FACC, FSCAI 
 
Supported by 
Boston Scientific 
 
 
Changes include: 
 
Page 27: Section 4.4.2 Exclusion Criteria 20 is changed from “Stents not fully apposed to vessel 
wall or overlapping stent segments” to “stents unapposed to either vessel wall or unapposed to 
overlapping stent segments. Apposed overlapping stents is not an exclusion” 
 
Page 29: Section 4.47 Blinding consists of correction of a grammatical error from "arms" to 
"arm"  
 
Page 29: Section 4.44 General Exclusion Criteria 9 is changed from “Has a history of 
gastrointestinal bleeding in the past 1 month prior to index procedure, or any history of 
hemorrhagic diathesis” to “Has a history of gastrointestinal bleeding in the past 3 months prior to 
index procedure, or any history of hemorrhagic diathesis.”  
 
 
Page 30: Table 1 Study Assessment of Hemoglobin A1C is completely removed 
 
Page 30: Table 1 Study Assessment Creatinine draw time Pre-Discharge is changed from 72 
hours post procedure +/- 24 hours to 72 hours post procedure +/- 48 hours   
 

 
68 
 
Page 30: Table 1 Study Assessment Duplex Ultrasound Pre-Discharge is changed from “The first 
duplex ultrasound can occur any time within 45 days after the index procedure” to “The first 
duplex ultrasound is optional and can occur any time within 45 after the index procedure.” 
 
Page 30: Section 4.52 Creatinine 
“Creatinine will be obtained and documented at baseline, 72 hours post procedure (+/-) 24 hours, 
and at 1 year follow-up visit” is change to “Creatinine will be obtained and documented at 
baseline, 72 hours post procedure (+/-) 48 hours, and at 1 year follow up visit.” 
 
Page 31:  Section 4.53 will be completely removed. 
 
Page 31:  Section 4.58 Duplex Ultrasound 
Second sentence will be changed from “DUS is required within 45 days of the index procedure 
(at either the pre-discharge or 30-Day visit), at 6 months, and at 1 year post-procedure” to “DUS 
is optional within 45 days of the index procedure (at either the pre-discharge or 30-Day visit), 
and required at 6 months, and at 1 year post-procedure.”  
 
Page 35/36: Table 3: Pre-Discharge Assessment Requirements 
Duplex Ultrasound* “First duplex ultrasound can occur any time within 45 days of the 
procedure” will be change to Duplex Ultrasound* “First duplex ultrasound is optional and can 
occur any time within 45 days of the procedure.” 
 
Page 35: Table 3: Pre-Discharge Assessment Requirements will have the addition of “Creatinine 
will be obtained and documented at baseline, 72 hours post procedure (+/-) 48 hours, and at 1 
year follow up visit.”