State of play – contemporary use of Drug Coated Balloon and … · PI-370371-2016-AA Clinical Study Overview: Ranger Name Ranger-SFA Primary Investigator Dierk Scheinert, MD Objective

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Contemporary use of DCBs, Ranger clinical trial and investigator sponsored research

Dierk Scheinert, MD Division of Interventional Angiology

University-Hospital, Leipzig, Germany

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• IMPORTANT INFORMATION: These materials are intended to describe common clinical considerations and procedural steps for the on-label use of referenced technologies as well as current standards of care for certain conditions. Of course, patients and their medical circumstances vary, so the clinical considerations and procedural steps described may not be appropriate for every patient or case. As always, decisions surrounding patient care depend on the physician’s professional judgment in light of all available information for the case at hand.

• BSC does not promote or encourage the use of its devices outside their approved labeling.

• The presenter’s experience with BSC products may not be interpreted or relied upon to support clinical claims about BSC devices or product comparison claims regarding BSC and competitive devices. The experiences of other users may vary.

• Results from case studies are not predictive of results in other cases. Results in other cases may vary.

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Disclosure

Within the past 12 months, I or my spouse/partner have had a financial interest/arrangement or affiliation with the

organization(s) listed below.

Advisory Board /Consultant:

Abbott, Biotronik, Boston Scientific, Cook Medical, Cordis, CR Bard, Gardia Medical, Medtronic/Covidien, TriReme Medical,

Trivascular, Upstream Peripheral Technologies

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Ranger™ Drug Coated Balloon

• Sterling balloon platform

• TransPaxTM coating technology

• Paclitaxel

• RangerTM Loading Tool • Designed to protect the drug coating

• Size matrix: • SFA: 4-8 mm; 30-100 mm • BTK: 2-4 mm; up to 150 mm

Introducer Sheath Balloon Catheter

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RangerTM Drug Coated Balloon: Coating Technology

TransPaxTM Technology Paclitaxel, Excipient: Citrate ester (acetyl tributyl citrate – ATBC)

• Designed to balance hydrophilic and hydrophobic properties

• Allow adhesion to the balloon during tracking and deployment

• Allow transfer to the vessel wall during balloon inflation

• Minimize particulate loss

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BSC Peripheral Drug Coated Balloon Clinical Program

Prospective, multicenter, RCT n = 106

Prospective, multicenter, single-arm, open label n= 123

Prospective, multicenter, single-blind, RCT n = ~350

Ranger DCB Global Pivotal

Ranger DCB SFA/PPA

China

Ranger DCB SFA: FIM

FPI: ~3Q 2016

FPI: ~4Q 2016

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Clinical Study Overview: Ranger

Name Ranger-SFA

Primary Investigator Dierk Scheinert, MD

Objective To prove the superior performance of the Ranger™ paclitaxel-coated PTA balloon catheter for angioplasty for femoropopliteal artery lesions when compared to non-coated balloons at six months post-procedure when comparing Late Lumen Loss (LLL).

Study Design Prospective, randomized, multicenter, controlled trial (2:1 Ranger Drug Coated Balloon vs. uncoated balloon)

Subjects Planned 105 patients with femoropopliteal artery lesions

Investigational Centers

11 sites (Germany, France, and Austria)

Primary Endpoint The primary endpoint is in-segment late lumen loss of the treated segment, as observed by angiography at six months post-procedure

EUDAMED CIV-13-07-011514 ; ClinicalTrials.gov NCT02013193.

Ongoing Ranger-SFA Clinical Study

http://clinicaltrials.gov/

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Ranger-SFA Study Patient Characteristics

Control Ranger DCB

N 30 63

Age (years) 67±9 68±8

Male 67% 73%

General Medical History

Diabetes mellitus 33% 40%

Hyperlipidemia 60% 71%

Hypertension 73% 83%

Smoking

Current 50% 40%

Previous 20% 46%

Cardiac History

Congestive heart failure 3% 6%

Coronary artery disease 43% 35%

Myocardial infarction 17% 14%

Renal History

Renal insufficiency 3% 13%

Peripheral Vascular History

Claudication 93% 98%

Other peripheral endovascular interventions 33% 38%

Peripheral vascular surgery 0% 11%

Albrecht, T. CIRSE 2015.

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Ranger-SFA Study Lesion Characteristics and Procedural Success

Control (N=30) Ranger DCB (N=63)

Lesion length (mm) 83 ± 66 73 ± 43

Lesion location

Proximal SFA 7% 19%

Middle SFA 47% 41%

Distal SFA 43% 35%

Proximal popliteal 3% 5%

Reference vessel diameter (mm) 5.1 ± 1.1 5.2 ± 0.7

Percent diameter stenosis 89% ± 11% 91% ± 9%

TASCII

A 77% 59%

B 23% 38%

C 0% 2%

D 0% 2%

Procedure Control Ranger DCB

Technical success 100% (30/30) 93.7% (59/63)

Procedural success 96.7% (29/30) 93.7% (59/63)

Residual angiographic stenosis 12% ± 12% 15% ± 17%


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Ranger-SFA Study Interim Safety Data – MAEs

As of August 2015, interim snapshot of SAE and MAEs • No SADE, no deaths or major amputations reported • 8 TLR in the Control group and 5 TLR in the Ranger Drug Coated Balloon group • Enrollment is ongoing and Monitoring of 93 patients not completed.

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Drug-Coated Balloons (Randomized Trials)

TLR Rates at 6 months*

9%

20%

7% 13% *11%

36%

65%

22% 22%

32%

0%

10%

20%

30%

40%

50%

60%

70%

DEBELLUM Katsanos PACIFIER LEVANT I RANGER

DCB Control

Clinical trials were not designed to be comparable, included for educational purposes only.

Biondi-Zoccai G, et al. Int J Cardiol. 2013;168(1):570-1.

*Data on file at Boston Scientific.

*Ranger Interim Trial analysis, monitoring ongoing

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Ranger All-Comer Registry Treatment of femoro-popliteal atherosclerotic lesions using the

Drug Eluting Balloon Ranger: An All Comers Registry

PI Michael Lichtenberg

Design Multicentre, all comer registry

Centres Germany (Dr. von Bilderling (Munich), Dr. Ranft, Dr. Niemöller (Bottrop), Dr. Grell (Trier) and Switzerland (Dr. Saucy, Lausanne)

Population Planned 180 patients

Primary Efficacy Endpoint

Major Adverse Events (MAE): composite of device or procedure related mortality and major target limb amputation at 6 months

Primary Safety Endpoint

Primary patency at 12 and 24 months, defined as freedom from ≥ 50% restenosis as indicated by duplex ultrasound peak systolic velocity ratio (PSVR) ≥2.4 in the target lesion with no re-intervention

Key Inclusion Criteria PAOD SFA – PIII, Rutherford II - V

These investigator-sponsored studies are supported by grant funding from Boston Scientific. Boston Scientific is not responsible for the collection, analysis or

reporting of these studies which remain the sole responsibility of the investigators. Information for the use in countries with applicable product registrations.

Investigator Sponsored Research Ranger SFA Registry

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Investigator Sponsored Research

Ranger SFA Registry Patient Demographics

Ranger DCB

N 134

Mean Age (years) 70

Male 63 %

ABI 0.70 (0.1-1.4)

General Medical History

Diabetes mellitus 34 %

Hyperlipidemia 95 %

Hypertension 93 %

Smoking

Current 34 %

Previous 43 %

Renal History

Renal insufficiency 20 %

Rutherford stage

II 18 %

III 70 %

IV 7 %

V 5%



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Ranger DCB

Lesion (n) 188

SFA 126

APOP 62

Lesion length (mm) 142 mm (6 – 223 mm)

Lesion location

Reference vessel diameter (mm) 5.3 mm ± 1.2

Percent diameter stenosis 89 % ± 11%

TASCII

A 19 %

B 22 %

C 21 %

D 38 %




Ranger SFA Registry Lesion Characteristics

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Procedure

TLD Number

1 69 %

2 20 %

3 6 %

4 2.5 %

5 0.5 %

Predilatation before DCB 81.2 %

Bail out stent rate 26%

Procedure Outcomes

Technical success for DCB only (no flow limiting dissection) 74 %

Procedural success DCB plus adjunctive therapy (stent) 100 %

Residual angiographic stenosis 10.7 %




Ranger SFA Registry Lesion Characteristics

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Ranger SFA Registry Interim Analysis

Interim results as of 20 January 2016:

20 patients with 6 month follow up

No TLR for 20 patients with 6M f/u

This investigator-sponsored study is supported by grant funding from Boston Scientific. Boston Scientific is not responsible

for the collection, analysis or reporting of these studies which remain the sole responsibility of the investigators. Information

for the use in countries with applicable product registrations.

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Historical patient population for Drug Coated Balloon studies?

• Historically Drug Coated Balloon trial/registry patients have represented a population with less-complex lesions • Primarily TASC A/B, lesion length

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• Severe calcium lesions have been limited by protocol in Drug Coated Balloon studies

Severe Calcification

Results from different trials are not directly comparable. Information provided for educational purposes.

1Micari A Et al. J Am Coll Cardiol Intv 2012; 2Tepe G et al. Circulation 2015; 3Zeller T et al. J Endovasc Therapy 2014; 4Schroeder H et al. Catheter

Cardiovasc Interv 2015; 5Laird J. Endovacsular Today Feb 2015; 6Ansel G. TCT 2015; 7Matsumura et al. J of Vasc Surg. Jul 2013; 8-9www.accessdata.fda.gov; 10www.endovascularmagazine.eu 2013; 11Powell, R. Charing Cross 2015; 12Dake MD et al. Circ Cardiovasc Interv 2011; 13 Müller-Hülsbeck, S. VIVA 2015.

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Stents used in Drug Coated Balloon studies

• Longer mean lesion length in Drug Coated Balloon studies is correlated with higher provisional stenting rate

Provisional Stenting in Randomized Controlled Trials may not be representative of actual stenting in studies due to study

design


1Werk M et al. Circulation 2008; 2Werk et al. Circ Cardiovasc Interv 2012; 3Tepe G et al. N Engl J Med 2008; 4icari A Et al. J Am Coll Cardiol Intv

2012; 5Tepe et al. Circulation 2015; 6Zeller T et al. J Endovasc Therapy 2014; 7Schmidt A. LINC 2013; 8Schroeder H et al. Catheter Cardiovasc

Interv 2015; 9Laird J. Endovacsular Today Feb 2015. 10Ansel G. TCT 2015.

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Effect of Occlusions in Drug Coated Balloon outcomes

• Higher rate of baseline occlusive lesions corresponded with higher TLR rates at 1 year


1Werk et al. Circ Cardiovasc Interv 2012; 2Tepe G et al. N Engl J Med 2008; 3Micari A Et al. J Am Coll Cardiol Intv 2012; 4Tepe G

et al. Circulation 2015; 5Zeller T et al. J Endovasc Therapy 2014; 6Schmidt A. LINC 2013; 7Schroeder H et al. Catheter

Cardiovasc Interv 2015;98Laird J. Endovacsular Today Feb 2015.

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• TLR rates rise over time following Drug Coated Balloon – Etiology?


1Albrecht T. LINC 2014; 2Tepe G et al. N Engl J Med 2008; 3Micari A Et al. J Am Coll Cardiol Intv 2013; 4Laird J. TCT 2015; 5Zeller T et al. J Endovasc Therapy 2014; 6Schmidt A. LINC 2013; 7Schroeder H et al. Catheter Cardiovasc Interv 2015;8Laird J. Endovacsular Today Feb 2015.

Effect of Occlusions in Drug Coated Balloon outcomes

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Investigator Sponsored Research Ranger Drug Coated Balloon

Prospective, multicentre, RCT 1:1 N = 50

Prospective, multicentre, RCT 1:1 N = 200

Prospective, RCT 1:1 (Head to Head) N = 150

Prospective, multicentre, registry N = 250

Feasibility, observational, angio F/U N= 30

Prospective, RCR 1:1 (Ranger vs PTA) N = 70

Haemodialysis AVG Rescue

Haemodialysis AVF Rescue

SFA RCT

SFA Registry

BTK Angiographic

BTK Clinical

Indication Expansion

Confirmatory

Exploratory



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Indication Studies DEVA

Improving Outcomes in Fistula Intervention: Drug Eluting Balloons in the Treatment of Arteriovenous Fistula Stenosis Drug Eluting balloon

Angioplasty in Vascular Access fistulas

Effects of Paclitaxel-coated PTA balloon on stenotic grafts

Study of the effects of Paclitaxel-coated PTA balloon, on hemodialysis grafts’ stenosis

PI Robert Jones PI Giuseppe Bacchini

Design Multicentre, randomised controlled time to reintervention

Design Single centre, randomised

Centres United Kingdom Centres Italy

Population 186 patients Population 50 patients


Time to composite of one or more of; re-intervention on single index lesion, >50% restenosis or fistula failure

Primary Endpoint

Primary patency rate: percentage of lesions that reach endpoint without the need for another intervention to maintain or restore patency and without a hemodynamically significant stenosis on DUS within 12 months

Secondary Efficacy Endpoint

Patency rates at 6 weeks and 3, 6 and 12 months will be compared between the DEB and standard balloon group.

Secondary Endpoints

Secondary patency rate: percentage of overall grafts’ survival Stenosis rate: episodes of stenosis of AVGs/year.



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Confirmation Studies Ranger All-Comer Registry

Treatment of femoro-popliteal atherosclerotic lesions using the Drug eluting Balloon Ranger (Boston):

An All Comers Registry

COMPARE I Pilot Treatment of Subjects with Symptomatic Femoropopliteal Artery

Disease with the Ranger™ DCB vs. the IN.PACT™ DCB

PI Michael Lichtenberg PI Dierk Scheinert

Design Multicentre, all comer registry Design Multicentre, RCT 1:1

Centres Germany, Austria, and Switzerland Centres Germany and Austria



Major Adverse Events (MAE): composite of device or procedure related mortality and major target limb amputation at 6 months


Patency rate after 1yr defined as absence of clinically driven TLR (due to symptoms and drop of ABI of ≥ 20% or > 0.15 when compared to post-procedure baseline) or restenosis with PVR > 2.4 evaluated by DUS


Primary patency at 12 and 24 months, defined as freedom from ≥ 50% restenosis as indicated by duplex ultrasound peak systolic velocity ratio (PSVR) ≥2.4 in the target lesion with no re-intervention


Composite of freedom from device and procedure-related death through 12m post procedure as well as freedom from both target limb major amputation and clinically-driven TVR




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Exploration Studies Ranger BTK

A safety and efficacy study to evaluate Ranger drug-eluting balloon for below the knee angioplasty in patients with critical limb ischemia

CRURAL DEB Randomized trial comparing drug coated balloon vs plain balloon

angioplasty in critical limb ischemia and treatment of long lesions in crural arteries

PI Marc Sapoval PI Torbjorn Fransson

Design Prospective, single centre, non-controlled, open-label

Design Prospective, single centre, randomized

Centres France Centres Sweden



Primary patency (no stenosis >50%) and Late Lumen Loss (LLL) of the Target Lesion measured by Quantitative Vascular Angiography (QVA) at 6 months adjudicated by independent core lab


12 month primary patency


Composite of all death and major amputation at 6 and 12 months

Secondary Endpoints

TLR, Event Free Survival, MRA analysis




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Conclusion

• Drug Coated Balloons provide increased efficacy in short to medium term over plain PTA

• Early safety data on Ranger Drug Coated Balloon is reassuring

• Ongoing Ranger SFA trials will provide further evidence in real world Ranger SFA study and head to head in COMPARE I

• Growing body of data on the effect of lesion characteristics on Drug Coated Balloon outcome – calcium, occlusion, length / bail-out stenting

• A tailored approach with available technologies could influence patient outcomes

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Contemporary use of DCBs, Ranger clinical trial and investigator sponsored research

Dierk Scheinert, MD Division of Interventional Angiology

University-Hospital, Leipzig, Germany

Documents

State of play – contemporary use of Drug Coated Balloon and … · PI-370371-2016-AA Clinical Study Overview: Ranger Name Ranger-SFA Primary Investigator Dierk Scheinert, MD Objective