Dierk Scheinert, MD. Department of Angiology University Hospital Leipzig, Germany

Transcription

1 The RANGER clinical trial programme: 12-month results from the RANGER RCT and first look at the COMARE I study of RANGER vs. IN.PACT for femoropopliteal lesions Dierk Scheinert, MD Department of Angiology University Hospital Leipzig, Germany

2 Disclosure Dierk Scheinert, MD Advisory Board /Consultant: Abbott, Biotronik, Boston Scientific, Cook Medical, Cordis, CR Bard, Gardia Medical/Allium, Medtronic, TriReme Medical, Trivascular, Upstream Peripheral Technologies

3 Next Generation DCB: Boston Scientific Ranger Sterling balloon platform TransPax TM coating technology Paclitaxel 2 µg/mm 2 Ranger TM DCB Loading Tool Designed to protect the drug coating Size matrix: SFA: 4-8 mm; mm BTK: 2-4 mm; up to 150 mm

4 BSC Peripheral DCB Clinical Program RANGER SFA (FIM) Prospective, multicenter, randomized n = 105 (12M follow up complete) Ranger II Global Pivotal Prospective, multicenter, RCT 3:1 (Ranger : PTA) n = 396 (Enrolling) Ranger DCB China Prospective, multicenter, single-arm n = 123 (Enrolling)

5 Ranger-SFA Study Patient Enrollment & Follow-up 105 patients treated at 10 study centers Assessed for eligibility (N=131) Enrolled and randomized (N=105) a Excluded Not meeting inclusion criteria (n=26) Died n=1 Withdrew n=2 Control (N=34) 6-month follow-up visit completed (n=25) Missed visit n=6 Evaluable angiography n=19 Withdrew n=2 12-month follow-up visit completed (n=28) Missed visit n=1 Ranger DCB (N=71) Withdrew n=2 6-month follow-up visit completed (n=63) Missed visit n=6 Evaluable angiography n=47 Died n=2 Withdrew n=1 12-month follow-up visit completed (n=59) Missed visit n=7 Scheinert, D. Charing Cross a Enrollment occurred after successful intraluminal guidewire crossing of the target lesion

6 Ranger-SFA Study Patient Characteristics Baseline clinical characteristics similar between Ranger and control groups Control (N=34) Ranger DCB (N=71) Age, y (mean±sd) 67 ± ± Men 68% 75% Diabetes mellitus 35% 39% COPD 15% 11% Hyperlipidemia 62% 69% Hypertension 76% 82% Smoking Current 50% 41% Previous 21% 45% P Congestive heart failure 2.9% 5.6% Coronary artery disease 38% 34% Myocardial infarction 15% 14% Cerebrovascular accident 2.9% 9.9% Renal insufficiency 2.9% 11% Bausback Y, et al. J Endovasc Ther. 2017;24(4):

7 Ranger-SFA Study Lesion (Core Lab) and Procedure Characteristics Similar lesion characteristics between Ranger and control groups Control Ranger DCB (N=34) (N=71) P Lesion length (mm) 60 ± ± Total occlusion 34% 34% Calcification None 16% 10% Mild 28% 27% Moderate 34% 24% Severe 22% 36% Location Proximal SFA 6% 17% Middle SFA 38% 44% Distal SFA 53% 36% Proximal popliteal 3% 3% TASC II A 69% 66% B 22% 27% C 6% 7% D 0.0% 0.0% % Diameter stenosis 82 ± ± Reference vessel diameter 4.5 ± ± Procedural Technical success (cross and dilate lesion with residual stenosis 30%) 94.1% 91.5% Procedural success (technical success without MAE within 24 hours) 91.2% 91.5% Post op % diameter stenosis (core lab) 26 ± ± Bailout stenting 12% 21% Bausback Y, et al. J Endovasc Ther. 2017;24(4):

8 MLD (mm) Change from Post-op (mm) Ranger-SFA Study Primary Efficacy Endpoint 6 Months LLL was significantly less for Ranger DCB than for control (P=.0017) o Primary endpoint was met Minimum Lumen Diameter P=.58 3,5 3,3 P=.92 0,88 0,79 * P= ,5 3,5 2,5 2 1,5 1 0,5 0 Late Lumen Loss (6 months) 0,76 * P= ,5-0,16 0 pre-op post-op 6 months Control (n=19) Ranger DCB (n=47) -1-1,5 Control (n=19) Ranger DCB (n=47) Bausback Y, et al. J Endovasc Ther. 2017;24(4): Scheinert, D. CIRSE 2016.

9 Primary Patency Rate Ranger-SFA Study Primary Patency 12 Months Kaplan Meier estimate of primary patency rate at 12 months: 86% Ranger DCB vs 56% Control Significantly greater time to failure (survival time) for Ranger DCB than control (log-rank P<.001) 100% 80% 86% 60% 40% Control Ranger 56% 20% At Risk Ranger DCB % Control Time since procedure (days) Scheinert, D. Charing Cross Primary patency defined as the percentage of lesions without a hemodynamically significant stenosis on duplex ultrasound (PSVR > 2.4) and without TLR or bypass of the target lesion.

10 Freedom from TLR Ranger-SFA Study Freedom from TLR 12 Months Kaplan Meier estimate of freedom from TLR at 12 months: 91% Ranger DCB vs 70% Control Significantly greater TLR-free time for Ranger DCB than control (log-rank P=.010) 100% 91% 80% 70% 60% 40% Control Ranger 20% 0% At Risk Ranger DCB Control Time since procedure (days) Scheinert, D. Charing Cross 2017.

11 Investigator Sponsored Research Ranger Drug Coated Balloon Indication Expansion DEVA Hemodialysis AVF Rescue Prospective, multicenter, RCT 1:1 N = 200 Confirmatory SFA RCT (COMPARE I) SFA Registry Prospective, RCT 1:1 (Ranger : InPact) N = 414 Prospective, multicenter, registry N = 180 Exploratory BTK Angiographic Feasibility, observational, angio F/U N = 30 BTK Clinical Prospective, RCT 1:1 (Ranger : 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.

12 Study objective First Head-to-Head RCT to compare two different Paclitaxel coated balloons (with different coatings and different paclitaxel dose density) in the treatment of patients with symptomatic femoropopliteal peripheral arterial disease Investigational device: Ranger Paclitaxel Coated PTA Balloon Catheter (Paclitaxel dose 2ug/mm2) Control device: IN.PACT Admiral or IN.PACT Pacific Drug Eluting Balloon (Paclitaxel dose 3.5ug/mm2)

13 Study Set-up Investigator Initiated Trial (IIT) Principal Investigator: Prof. Dierk Scheinert Study sponsor: University of Leipzig Funded through a research grant of Boston Scientific Independent monitoring with 100% source data verification Independent corelab for angio and duplex Clinical events committee

14 Study Design Prospective, multicenter, randomized trial Randomization 1:1 Phase 1: Pilot Study (150 patients) Phase 2: Extension (up to 414 patients) for testing of a formal non-inferiority hypothesis Stratification according to lesion length Follow-up clinical visits at 6, 12, 24 months Protocol pre-specified interim analysis of the first 150 patients (COMPARE Pilot) after 12 months of follow-up -> Presented today

15 Study Sites COMPARE Pilot (n=15) Angiologikum Hamburg-Dr. Sixt Herz- und Gefässzentrum Bad Bevensen Dr. Euringer Franziskus KH Berlin- Dr. Brechtel Jüdisches KH Berlin-Dr. Schröder St. Gertrauden KH-Dr. Langhoff Diakoniewerk Halle Dr. Hübner KKH Torgau Dr. Maiwald KKH Eilenburg Dr. Ali Universität Leipzig-Prof. Scheinert Uniklinik Dresden-Prof. Weiss KH Dresden-Friedrichstadt-Dr. Stelzner Medinos Klinik Sonneberg Dr. Thieme Klinikum Karlsbad-Langensteinbach Prof. Blessing Herzzentrum Bad Krozingen-Prof. Zeller Romed Kliniken Rosenheim Prof. Tepe

16 Key In- and Exclusion criteria Symptomatic PAD Rutherford 2-4 Stenosis (>70%) or occlusion of the SFA or proximal popliteal artery De-novo or restenotic lesions (no ISR) No severe calcification Lesion length up to 30 cm Stratification in 3 groups </=10 cm >10cm and </=20cm >20cm and </=30cm At least one patent BTK outflow vessel to the foot

17 Study Endpoints Primary efficacy endpoint: Patency rate after 12 months defined as absence of clinically driven TLR (due to symptoms and drop of ABI of 20% or > 0.15 when compared to post-procedure) or restenosis with PVR > 2.4 evaluated by Duplex Ultrasound Primary safety endpoint: Composite of freedom from device and procedure-related death through 12 months post procedure as well as freedom from both target limb major amputation and clinically-driven target vessel revascularization

18 Patient flow diagram 150 Patients Randomized Ranger DCB 74 patients 1 withdrawal 1 death IN.PACT DCB 76 patients 2 withdrawal 6-months visit 68/72 patients: 4 missed 66 ultrasound readings 6-months visit 71/74 patients: 3 missed 66 ultrasound readings 5 withdrawals 3 withdrawals 12-months visit 66/67 patients: 1 missed; 64 ultrasound readings 12-months visit 65/71 patients: 6 missed; 60 ultrasound readings

19 Baseline Demographics of first 150pts RANGER DCB (n=74) IN.PACT DCB (n=76) p-value Age, y 68.6± ± Male gender 44 (60%) 53 (70%) 0.2 Weight, kg 77.9± ± Prior myocardial infarction 11 (15%) 5 (7%) 0.2 Coronary artery disease 21 (29%) 21 (28%) 0.9 Cerebrovascular disease 12 (16%) 8 (11%) 0.3 Hyperlipidemia 50 (68%) 57 (75%) 0.3 Hypertension 65 (88%) 68 (90%) 0.8 Renal Insufficiency 12 (16%) 14 (18%) 0.6 Smoking 0.4 Current 32 (43%) 38 (50%) Previous 27 (37%) 20 (26%) Diabetes mellitus 25 (34%) 28 (37%) 0.7 Claudication (RC 2-3) 69 (93%) 71 (94%) 0.6 Critical limb ischemia (RC 4) 5 (7%) 5 (6%) Data are given as mean±sd or number (%).

20 Lesion Characteristics* of first 150pts RANGER DCB IN.PACT DCB (n=74) (n=76) p-value Target lesion length, mm 117.4± ± Diameter stenosis, % 82.7± ± Reference vessel diameter, mm 4.9± ± Minimal vessel diameter, mm 0.8± ± Total occlusion 29 (39.2%) 34 (44.7%) 0.5 Total occlusion length, mm 110.9± ± Prox. popliteal involvement 14 (18.9%) 11 (14.5%) 0.2 Lesion calcification 0.7 None 8 (11.1%) 8 (10.7%) 0.7 Mild 21 (29.2%) 18 (24%) Moderate 1 (1.4%) 0 (0%) Moderately severe 25 (34.7%) 33 (44%) Severe 17 (23.6%) 16 (21.3%) 0-1 patent run off vessels 20 (26.9%) 25 (32.9%) 0.6 * Per angiographic core lab assessment. Data are given as mean±sd or number (%).

21 Procedural Outcomes* of first 150pts RANGER DCB (n=74) IN.PACT DCB (n=76) p-value Bailout stent placement 19 (25.7%) 17 (22.4%) 0.6 MVD postprocedure, mm 3.6± ± Diameter stenosis postprocedure, % 25.8± ± Residual stenosis > 30% 26 (35.1) 29 (38.2) 0.7 Dissection 70 (92.1%) 70 (94.6%) 0.7 Type A/B, n (%) 54 (77.1%) 44 (62.8) 0.1 Type C-F, n (%) 16 (22.9%) 26 (37.2%) Complications Embolic event 2 (2.7%) 1 (1.3%) AV-Fistel (local) 5 (6.8%) 5 (6.6%) Target Vessel Perforation 1 (1.4%) 1 (1.3%) * Per angiographic core lab assessment. Data are given as mean±sd or number (%).

22 Primary efficacy endpoint: Patency rate* 180days 210days 365days 410days IN.PACT 0.97± ± ± ±0.15 RANGER 0.94± ± ± ±0.05 Days *Patency: defined as absence of clinically driven TLR or restenosis with PVR>2.4 evaluated by duplex ultrasound scan; both per core lab assessment.

23 Summary Head-to-head comparison of Ranger DCB vs. IN.PACT DCB in femoropopliteal interventions Complex real world lesion subset with lesion length ~12cm and proportion of CTO`s ~40% Excellent efficacy at 1 year of both tested DCB in the interim analysis of first 150 randomized patients Similar primary patency of the low-dose Ranger DCB (2ug/mm2) compared to the Inpact DCB (3.5ug/mm2) during the 1year surveillance period Recruitment of full study cohort (414 patients) will be finished Q2/2018

24 The RANGER clinical trial programme: 12-month results from the RANGER RCT and first look at the COMARE I study of RANGER vs. IN.PACT for femoropopliteal lesions Dierk Scheinert, MD Department of Angiology University Hospital Leipzig, Germany