Randomised Trials of Carotid Interventions Will the Changing Technology of Membrane Mesh Stents Shape The Future?

Transcription

1 Randomised Trials of Carotid Interventions Will the Changing Technology of Membrane Mesh Stents Shape The Future? Dr Sumaira Macdonald MBChB (Comm.), FRCP, FRCR, PhD, EBIR Vascular Interventional Radiologist Chief Medical Officer, Silk Road Medical, Sunnyvale, California ACST2 April 2016

2 Lecture Plan: Perils of trialing a rapidly evolving technology within an RCT construct Stent design considerations Impact of stent design parameters on outcomes Procedural stroke hazard Surrogates (DWMRI new white lesions) Current membrane mesh stent platforms

3 Perils of trialing a rapidly evolving technology within an RCT construct Leaving no questions unanswered Criticisms of the use of suboptimal/obsolete technology Selection bias Anatomy Mind share

4 ACST2 & Membrane Mesh Stents 14 ROADSAVER 5 CGUARD Likely too small a final number of cases with membrane mesh stents for a valid sub-set analysis Is a membrane mesh stent a relevant consideration for a purely asymptomatic patient population?

5 Stent Design:

6 Cell Design - CAS Proximal PROTÉGÉ RX (Tapered, 8-6mm) RX ACCULINK TM (Tapered, 8-6 mm) Xact (Tapered, 8-6mm) PRECISE (Straight, 8 mm) WALLSTENT (Straight, 8 mm) Pore Diam. (mm) Pore Size (mm2) Cell Area (mm2) Distal PROTÉGÉ RX (Tapered, 8-6 mm) RX ACCULINK TM (Tapered, 8-6mm) (Tapered, 8-6mm Xact) PRECISE (Straight, 8 mm) WALLSTENT (Straight, 8 mm) Pore Diam. (mm) Pore Size (mm2) Cell Area (mm2) Bersin RM TCT 2008

7 The Impact of Stent Design Parameters On Outcomes: Procedural Stroke Hazard

8 Delayed Stroke & Death At 1-30 Days Stratified By Stent Design 2/3 of events delayed Bosiers et al. Eur J Vasc Endovasc Surg 2007;33:135

9 Delayed Stroke & Death At 1-30 Days Stratified By Stent Design & Symptom Status Bosiers M e al. Does Free Cell Area Influence the Outcome in Carotid Artery Stenting? EJVES 2007;33:

10 Jim J et al. JVS 2011;54:71-79

11 Delayed Stroke & Death At 1-30 Days Stratified By Stent Design In Symptomatic Patients:

12 Increased Neurologic Events With Open Cell Stents SPACE Trial Jansen O et al. Stroke 2009;40:

13 Increased Neurologic Events With Open Cell Stents ICSS Trial Doig D et al ICSS subset analysis: In Press

14 The Impact of Stent Design Parameters On Outcomes: Surrogate Markers (DWMRI Brain & TCD)

15 32 studies: 1363 CAS & 754 CEA Ipsilateral DWI lesions: 51% open cell stents 31% closed cell stents p < 0.01

16 14 asymptomatic patients 1:1 RCT eptfe covered membrane stent (symbiot) vs. Wallstent Microembolisation (TCD) and DWI Schillinger et al JEVT 2006;13:

17 Symbiot: median 1 MES / patient (IQR 0-4) Wallstent: median 6 MES / patient (IQR 3-8) p = 0.04

18 N = 96 (76 symptomatic) Transfemoral filter protected (FilterWire N =86, AngioGuard N = 5) Randomly allocated to: PRECISE (N=48) WALLSTENT (N=48) Park KY et al. J Neurosurg 2013;21:1-6

19 Outcomes Stratifed By Stent Design:

20 Available Membrane Mesh Stent Platforms

21 GORE SCAFFOLD

22 500 micron pore size

23 Modified Chandler loop with recirculating blood Heparin bonded devices thrombus free after one hour exposure to human blood Untreated control contained adherent thrombus Coagulation biomarker prothrombin fragment 1 & 2 (F1 & 2) revealed significantly lower levels with heparin bonded stent

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25 TERUMO/MICROVENTION ROADSAVER

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27 InspireMD CGUARD

28 N = day endpoint S/D/MI 2 0 endpoint DWMRI pre/48 hours/30 days JACC Interventions 2015;8:

29 S/D/MI at 30-days = 0

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32 CONCLUSIONS: Closed cell stents are associated with fewer DWI lesions than open cell stents Membrane mesh stents are associated with fewer TCD MES & DWMRI lesions than closed cell stents Closed cell stents are consistently associated with lower stroke & death than open cell stents IN SYMPTOMATIC PATIENTS with no meaningful difference in asymptomatic patients

33 CONCLUSIONS: Likely too small a final number of cases with membrane mesh stents in ACST2 for a valid sub-set analysis Is a membrane mesh stent a relevant consideration for a purely asymptomatic patient population?

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35 TRIAL DESIGN COMPARISON Trial CARENET SCAFFOLD CLEAR-ROAD Status CE Mark granted March 2013; Enrollment completed; Present results at TCT Sept Enrolled first patient Sep. 2013; trial undergoing midpoint review Started 2014 Sites 8 (EU; Germany, Poland, Belgium) 50 (US, EU, Japan) EU Subjects Study Design Population Primary Endpoint Prospective, multi-center, international, open label, singlearm, non-randomized clinical trial Sx 50% or ASx 80% stenosis MAE (1) at 30 days; ipsilateral stroke (31 days to 1 year) and DW-MRI pre-, post-procedure and at 30 days; ultrasound at 30 days and 1 year Prospective, multi-center, singlearm study comparing Gore to CEA performance goal High surgical risk for CEA: Sx 50% or ASx 80% stenosis; single restenotic lesion at bifurcation MAE (1) at 30 days; ipsilateral stroke (31 days to 1 year) Prospective, multi-center, open label, single-arm, nonrandomized clinical trial MAE (1) at 30 days Secondary endpoint FU at 1 year & duplex Expected Completion COMPLETED NO S/D/MI at 30 days Restarted after interim analysis at 100 pts protocol revisions submitted to FDA?Started Primary Investigator(s) J. Schofer W. Gray, P. Schneider M. Bosiers (1) MAE defined as death, stroke or MI.

36 Membrane mesh carotid stent FEATURE comparison Description InspireMD CGuard Single fiber knitted mesh wrapped on stent platform Gore Carotid Stent [Scaffold] Mesh-coated stent Terumo CASPER/ Roadsaver Double layer braided micro-mesh and stent Stent Material Nitinol Nitinol Nitinol Mesh Material PET (Poly ethylene terephthalate) eptfe (expanded polytetrafluoroethylene) lattice Nitinol micro-mesh Coating None CBAS heparin None Cell Type Open cell Open cell Closed cell Pore Size (µm) Fiber Size (µm) 20 Diameters (mm) (1) Stent Length (mm) 30, 40, 30 (taper), 40 (taper) (1) 20/25 through 30/43 (2) Sheath Compatibility Guide Catheter Compatibility 5Fr (0.074 ) / 6Fr (0.080 ) 5Fr (0.074 ) 7Fr (0.074 ) Deployment Handle with unidirectional wheel Push-pull (1) Represents unconstrained dimensions for both Gore and Terumo devices (2) 20/25 represents 20mm micromesh layer stent length and 25mm overall stent length

37 Muller-Hulsbeck S et al. JEVT 2009;16:

38 Maximum number of fitted-in circles at the proximal, middle & distal parts of the stents Fourth generation carotid stent

39 Sphere penetration force:

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41 Case courtesy of Claudio Schonholz Future stent designs likely to include some type of mesh

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43 Black = Open Cell Gray = Closed Cell

44 Multivariate Analysis for DWMRI Lesions (Symptomatic Patients Only):