Update from the Tryton IDE study

Transcription

1 Update from the Tryton IDE study Maciej Lesiak EBC Athens

2 The Tryton Bifurcation Trial: A randomized comparison of a provisional one-stent vs. a dedicated two-stent strategy for true bifurcation coronary lesions Martin B. Leon, MD for the Tryton Bifurcation Trial Investigators Columbia University Medical Center Cardiovascular Research Foundation New York City JACC 2015; 65: Wednesday, October 30, 2013

3 Tryton Pivotal Trial Design Baseline Angiography Eligible for Randomization ê Tryton side branch + DES (main vessel) ê N = 704 ê DES (main vessel) + Provisional side branch ê Clinical F/U at 9 months ê Angiographic F/U at 9 months ê IVUS F/U at 9 months TVF Primary Endpoint % DS side branch n~374 IVUS Cohort n~96 ê Clinical F/U at 9 months ê Angiographic F/U at 9 months ê IVUS F/U at 9 months

4 Medina Classification (Core Lab) T: 49.2% P: 42.1% T: 15.8% P: 16.0% T: 24.9% P: 28.1% True Bifurcation T: 89.9% P: 86.2% T: 1.4% P: 2.6% T: 2.3% P: 4.9% T: 2.8% P: 4.0% T: 3.4% P: 2.3% P = Provisional T = Tryton

5 Tryton Pivotal RCT True Bifurcation 88% of Recruited Population

6 Tryton Pivotal RCT Side Branch RVD 60% below Inclusion Criteria

7 Tryton Pivotal RCT: Target Vessel Failure Primary Endpoint: Missed! Non Hierarchical

8 % Side Branch %DS (In-segment) Secondary Endpoint Provisional Tryton P=0.002 Secondary Superiority Endpoint Met

9 Additional Side Branch Stents (Site Reported) Provisional (n= 349) Tryton (n= 355)

10 Stent Thrombosis (ARC) 9-month Follow-up Event - % (n) Provisional Tryton P-Value (N=349) (N=355) All to 270 days definite 0.3 (1) 0.6 (2) 1.00 probable 0 0 na def + prob 0.3 (1) 0.6 (2) 1.00 Early (0-30 days) definite 0.3 (1) 0.6 (2) 1.00 probable 0 0 na def + prob 0.3 (1) 0.6 (2) 1.00 Late ( days) definite 0 0 na probable 0 0 na def + prob 0 0 na Overall = 0.4%

11 Conclusion TRYTON trial The Tryton two-stent strategy in true bifurcations (88%) compared with the provisional strategy (8.0% side branch stents) did not meet the non-inferiority clinical endpoint (TVF), due to a relatively higher frequency of small peri-procedural CK-MB elevations. However, both strategies were safe (rare clinically significant MIs and stent thrombosis) and both had low 9-month clinically-driven TVR (P:3.6%,T:4.7%). Tryton improved side branch % diameter stenosis at FU (secondary endpoint; P=0.002)

12 Tryton Pivotal Study Why it failed?

13 Target Vessel Failure (TVF) Primary Endpoint % P= P = , ~86% MIs peri-procedural , TVF Cardiac Death CK >3x ULN Clinically Driven TVR ( Spontaneous MI) P = ,6 Provisional Tryton 4,7 Non Hierarchical

14 The influence of peri-procedural MI (CK-MB > 3xULN) on clinical two years Peri-Proc. MI N=81 No Peri-pro. MI N=623 P value Death (all cause) 0% 2.6% 0.15 Cardiac death 0% 0.3 % 0.62 TVR 12.9% 8.6% 0.17

15 Side Branch RVD (Core Lab) Frequency # Pre Procedure Side Branch Size

16 Provisional TRYTON Stent P for interaction=0.006 TVF P for interaction=0.020 Target Vessel MI Event Rate (%) p=0.002 p= ,7 19,2 15,6 12,1 10,3 11,3 9,2 9,2 P for interaction=0.318 Clinically Driven TVR 3,1 5,5 4,3 3,5 20/195 44/203 22/141 16/141 18/195 39/203 17/141 13/141 6/195 11/201 6/139 5/141 <2.25 mm 2.25 mm <2.25 mm 2.25 mm <2.25 mm 2.25 mm Side Branch Size

17 % Target Vessel Failure (TVF) Side Branch 2.25 mm P= ,8 TVF Diff (95% CI) = -4.3%(-12.2,3.5%) 10,5 0 0 P = ,0 TVF Cardiac Death Target Vessel MI Clinically Driven TVR 8,4 P = ,2 Provisional Tryton (21/142) (15/143) (17/142) (12/143) (6/142) (5/143) 3,5 Provisional N=143 Tryton N=146 Non Hierarchical

18 % Angiographic Outcomes (QCA) Side Branch 2.25 mm 9 Months Provisional N=81 Tryton N=64

19 Side Branch Bail Out Stenting Nearly Eliminated in Tryton Group Side Branch 2.25 mm Provisional (n= 143) Tryton (n= 146)

20 Conclusion Intended Cohort 2.25 mm Analysis A significant interaction exists between the diameter of the SB, the PCI strategy, and the occurrence of adverse events (TVF, TV-MI) in true bifurcation lesion Improved clinical and angiographic outcomes with Tryton in protocol-targeted SB ( 2.25 mm side branches) TVF (Safety Endpoint): Excluded Non-Inferiority Delta Derived from the Full Cohort Analysis Plan (Δ = 5.5) % Diameter Stenosis (Efficacy endpoint) p=0.004: Met

21 Conclusion (2) Intended Cohort 2.25 mm Analysis This post-hoc analysis of the intended population of bifurcation lesions with large side branches ( 2.25 mm by angio core lab ~2.5 mm visual) supports the safety (TVF within the pre-determined non-inferiority delta) and efficacy (significant reduction in %DS at 9 months) of the TRYTON SB dedicated bifurcation stent compared to a provisional stenting strategy.

22 IDE Extended Access or Confirmatory Study The Tryton Pivotal

23 Tryton Bifurcation Study: Intended Cohort post hoc analysis In patients who met selection criteria, when compared to Provisional Control, Tryton: All pre-specified Success Criteria Met Reduced MACE (within non-inferiority window) Improved angiographic results Markedly Reduced Unplanned (Bailout) Side Branch Stent

24 Tryton Confirmatory Study: Purpose Developed in close collaboration with FDA To further validate the post hoc intended cohort analysis (2.5 mm visual estimate) To demonstrate the ability of operators to identify appropriate lesions To prospectively confirm the acceptable periprocedural safety profile of the Tryton stent as seen in the post hoc analysis

25 PI: Martin B. Leon MD Trial Schematic (single arm) Review Clinical Selection Criteria/Obtain Informed Consent ê Base Line Angiography Review Angiographic Selection Criteria (SB diameter assessment after pre-dilatation) ê ITT begins when Tryton enters the guide catheter N = 133 SB: Tryton ê Main: Workhorse DES Primary End point: Periprocedural MI >3X URL 48hrs post PCI ê Clinical F/U 30 days ê Clinical F/U 1 year

26 Protocol Overview Single Arm Registry: Tryton + DES in the treatment of complex bifurcation lesions N = 133 Primary Endpoint: Periprocedural MI of 3X URL post PCI Secondary Endpoint: Same as IDE without Angio/IVUS sub studies Follow-up: 30 days and 1 year Up to 30 Centers North America and Europe Principal Investigator: Martin B. Leon M.D.

27 Major Selection Criteria: Complex bifurcation lesion requiring side branch treatment Inclusion Complex Bifurcation Lesion Angiographic Disease in BOTH Main & Side Branch Medina (1.1.1, 0.1.1, 1.0.1) by visual estimate Significant Side-Branch Disease >50% stenosis by visual estimate Exclusion Main branch Dia: <2.5 or > 4.0 mm Side branch Dia: <2.5 or > 3.0 mm Diffuse Side branch Disease (>5 mm from origin) Trifurcation Lesion Lesion involving the Left Main Coronary Artery Excessive lesion calcification PCI-Stenting of up to 2 distinct lesions within non-study vessel permitted providing

28 Tryton EXTENDED Access Registry Angiographic Inclusion Criteria Single de novo true bifurcation lesion in a native coronary artery involving both the main vessel and the side branch (Medina classification 1.1.1, 1.0.1, or by visual assessment) Symptoms or objective evidence of ischemia Vessel diameter: main vessel 2.5 mm and 4.0 mm; side branch 2.5 mm and 3.5 mm Lesion length: main vessel 28 mm; side branch 5 mm Limited treatment of multi-vessel disease and staging, per protocol (after successful treatment of 2 non-complex, non-target lesions) SB diameter assessment after pre-dilatation

29 Performance Goal: Sample Size Calculation Powered Endpoint: Peri-procedural MI Provisional Observed Rate in IDE 11.9% Tryton Anticipated Rate 8.9% Power: 90% Delta: 6.0% Performance Goal: 17.9% N = 133 Anticipates 4% missing CKMB / SB RVD <2.25mm QCA

30 Confirmatory Study Results* *Preliminary Results presented PRIOR TO DATA LOCK Clinical Data (HCRI): 130/133 Data Available Angio Data (CRF): 110/133 Angios reviewed

31 Tryton IDE XA Enrollment 28 Centers US =13, Euro =

32 Monday October 12 1:30 pm Featured Clinical Research I: TRYTON-IDE XA Registry: Evaluation of a Dedicated Stent in the Treatment of True Bifurcation Lesions With Large Side Branches - Philippe Généreux

33 Thank you