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

Transcription

1 Contemporary use of DCBs, Ranger clinical trial and investigator sponsored research Dierk Scheinert, MD Division of Interventional Angiology University-Hospital, Leipzig, Germany

2 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.

3 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

4 Ranger Drug Coated Balloon Sterling balloon platform TransPax TM coating technology Paclitaxel Ranger TM Loading Tool Designed to protect the drug coating Size matrix: SFA: 4-8 mm; mm BTK: 2-4 mm; up to 150 mm Introducer Sheath Balloon Catheter

5 Ranger TM Drug Coated Balloon: Coating Technology TransPax TM 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

6 BSC Peripheral Drug Coated Balloon Clinical Program Ranger DCB SFA: FIM Prospective, multicenter, RCT n = 106 Ranger DCB SFA/PPA China FPI: ~3Q 2016 Prospective, multicenter, single-arm, open label n= 123 Ranger DCB Global Pivotal FPI: ~4Q 2016 Prospective, multicenter, single-blind, RCT n = ~350

7 Ongoing Ranger-SFA Clinical Study Clinical Study Overview: Ranger Name Ranger-SFA Primary Investigator Dierk Scheinert, MD Objective Study Design Subjects Investigational Centers Primary Endpoint To prove the superior performance of the Ranger paclitaxel-coated PTA balloon catheter for angioplasty for femoropopliteal artery lesions when compared to noncoated balloons at six months post-procedure when comparing Late Lumen Loss (LLL). Prospective, randomized, multicenter, controlled trial (2:1 Ranger Drug Coated Balloon vs. uncoated balloon) Planned 105 patients with femoropopliteal artery lesions 11 sites (Germany, France, and Austria) The primary endpoint is in-segment late lumen loss of the treated segment, as observed by angiography at six months post-procedure EUDAMED CIV ; ClinicalTrials.gov NCT

8 Ranger-SFA Study Patient Characteristics Control Ranger DCB N 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.

9 Ranger-SFA Study Lesion Characteristics and Procedural Success Control (N=30) Lesion length (mm) 83 ± ± 43 Lesion location Ranger DCB (N=63) Proximal SFA 7% 19% Middle SFA 47% 41% Distal SFA 43% 35% Proximal popliteal 3% 5% Reference vessel diameter (mm) 5.1 ± ± 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% Albrecht, T. CIRSE 2015.

10 Ranger-SFA Study Interim Safety Data MAEs PI AA Jan 2016-AA 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. Albrecht, T. CIRSE 2015.

11 Drug-Coated Balloons (Randomized Trials) TLR Rates at 6 months* 70% 60% 50% 40% 30% 20% 10% 0% 65% 36% 20% 9% 7% DCB Control 32% 22% 22% 13% *11% DEBELLUM Katsanos PACIFIER LEVANT I RANGER *Ranger Interim Trial analysis, monitoring ongoing Clinical trials were not designed to be comparable, included for educational purposes only. Biondi-Zoccai G, et al. Int J Cardiol. 2013;168(1): *Data on file at Boston Scientific.

12 Investigator Sponsored Research Ranger SFA Registry Ranger All-Comer Registry Treatment of femoro-popliteal atherosclerotic lesions using the Drug Eluting Balloon Ranger: An All Comers Registry PI Design Centres Population Primary Efficacy Endpoint Primary Safety Endpoint Key Inclusion Criteria Michael Lichtenberg Multicentre, all comer registry Germany (Dr. von Bilderling (Munich), Dr. Ranft, Dr. Niemöller (Bottrop), Dr. Grell (Trier) and Switzerland (Dr. Saucy, Lausanne) Planned 180 patients Major Adverse Events (MAE): composite of device or procedure related mortality and major target limb amputation at 6 months 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 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.

13 Investigator Sponsored Research Ranger SFA Registry Patient Demographics Ranger DCB N 134 Mean Age (years) 70 Male 63 % ABI 0.70 ( ) 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% 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.

14 Investigator Sponsored Research Ranger SFA Registry Lesion Characteristics PI AA Jan 2016-AA 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 % 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.

15 Investigator Sponsored Research Ranger SFA Registry Lesion Characteristics PI AA Jan 2016-AA Procedure TLD Number 1 69 % 2 20 % 3 6 % % % 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 % 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.

16 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.

17 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 <10 cm Less calcification Less occlusions Simple Complex A* B C D POBA DCB STENTS: Bare, Drug-Eluting, Covered SURGERY * TransAtlantic Inter-Society Consensus (TASC ) II Lesion Classification (Type A, B, C, D ) for peripheral artery disease

18 Severe Calcification Severe calcium lesions have been limited by protocol in Drug Coated Balloon studies Results from different trials are not directly comparable. Information provided for educational purposes. 1 Micari A Et al. J Am Coll Cardiol Intv 2012; 2 Tepe G et al. Circulation 2015; 3 Zeller T et al. J Endovasc Therapy 2014; 4 Schroeder H et al. Catheter Cardiovasc Interv 2015; 5 Laird J. Endovacsular Today Feb 2015; 6 Ansel G. TCT 2015; 7 Matsumura et al. J of Vasc Surg. Jul 2013; ; 11 Powell, R. Charing Cross 2015; 12 Dake MD et al. Circ Cardiovasc Interv 2011; 13 Müller-Hülsbeck, S. VIVA 2015.

19 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 1 Werk M et al. Circulation 2008; 2 Werk et al. Circ Cardiovasc Interv 2012; 3 Tepe G et al. N Engl J Med 2008; 4 icari A Et al. J Am Coll Cardiol Intv 2012; 5 Tepe et al. Circulation 2015; 6 Zeller T et al. J Endovasc Therapy 2014; 7 Schmidt A. LINC 2013; 8 Schroeder H et al. Catheter Cardiovasc Interv 2015; 9 Laird J. Endovacsular Today Feb Ansel G. TCT Results from different trials are not directly comparable. Information provided for educational purposes.

20 Effect of Occlusions in Drug Coated Balloon outcomes Higher rate of baseline occlusive lesions corresponded with higher TLR rates at 1 year Results from different trials are not directly comparable. Information provided for educational purposes. 1 Werk et al. Circ Cardiovasc Interv 2012; 2 Tepe G et al. N Engl J Med 2008; 3 Micari A Et al. J Am Coll Cardiol Intv 2012; 4 Tepe G et al. Circulation 2015; 5 Zeller T et al. J Endovasc Therapy 2014; 6 Schmidt A. LINC 2013; 7 Schroeder H et al. Catheter Cardiovasc Interv 2015; 98 Laird J. Endovacsular Today Feb 2015.

21 Effect of Occlusions in Drug Coated Balloon outcomes TLR rates rise over time following Drug Coated Balloon Etiology? Results from different trials are not directly comparable. Information provided for educational purposes. 1 Albrecht T. LINC 2014; 2 Tepe G et al. N Engl J Med 2008; 3 Micari A Et al. J Am Coll Cardiol Intv 2013; 4 Laird J. TCT 2015; 5 Zeller T et al. J Endovasc Therapy 2014; 6 Schmidt A. LINC 2013; 7 Schroeder H et al. Catheter Cardiovasc Interv 2015; 8 Laird J. Endovacsular Today Feb 2015.

22 Investigator Sponsored Research Ranger Drug Coated Balloon Indication Expansion Haemodialysis AVG Rescue Haemodialysis AVF Rescue Prospective, multicentre, RCT 1:1 N = 50 Prospective, multicentre, RCT 1:1 N = 200 Confirmatory SFA RCT SFA Registry Prospective, RCT 1:1 (Head to Head) N = 150 Prospective, multicentre, registry N = 250 Exploratory BTK Angiographic Feasibility, observational, angio F/U N= 30 BTK Clinical Prospective, RCR 1:1 (Ranger vs PTA) N = 70 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.

23 Investigator Sponsored Research Ranger Drug Coated Balloon DEVA Improving Outcomes in Fistula Intervention: Drug Eluting Balloons in the Treatment of Arteriovenous Fistula Stenosis Drug Eluting balloon Angioplasty in Vascular Access fistulas Indication Studies 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 Centres United Kingdom Centres Italy Population 186 patients Population 50 patients Single centre, randomised Primary Efficacy Endpoint Time to composite of one or more of; reintervention 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. 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.

24 Investigator Sponsored Research Ranger Drug Coated Balloon Ranger All-Comer Registry Treatment of femoro-popliteal atherosclerotic lesions using the Drug eluting Balloon Ranger (Boston): An All Comers Registry Confirmation Studies PI Michael Lichtenberg PI Dierk Scheinert COMPARE I Pilot Treatment of Subjects with Symptomatic Femoropopliteal Artery Disease with the Ranger DCB vs. the IN.PACT DCB Design Multicentre, all comer registry Design Multicentre, RCT 1:1 Centres Germany, Austria, and Switzerland Centres Germany and Austria Population 250 patients Population 150 patients Primary Efficacy Endpoint Major Adverse Events (MAE): composite of device or procedure related mortality and major target limb amputation at 6 months Primary Efficacy Endpoint 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 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 Primary Safety Endpoint Composite of freedom from device and procedurerelated death through 12m post procedure as well as freedom from both target limb major amputation and clinically-driven TVR 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.

25 Investigator Sponsored Research Ranger Drug Coated Balloon Ranger BTK A safety and efficacy study to evaluate Ranger drug-eluting balloon for below the knee angioplasty in patients with critical limb ischemia Exploration Studies PI Marc Sapoval PI Torbjorn Fransson CRURAL DEB Randomized trial comparing drug coated balloon vs plain balloon angioplasty in critical limb ischemia and treatment of long lesions in crural arteries Design Prospective, single centre, non-controlled, openlabel Design Prospective, single centre, randomized Centres France Centres Sweden Population 30 patients Population 70 patients Primary Efficacy Endpoint 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 Primary Efficacy Endpoint 12 month primary patency Primary Safety Endpoint Composite of all death and major amputation at 6 and 12 months Secondary Endpoints TLR, Event Free Survival, MRA analysis 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.

26 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

27 Contemporary use of DCBs, Ranger clinical trial and investigator sponsored research Dierk Scheinert, MD Division of Interventional Angiology University-Hospital, Leipzig, Germany