V. Dorrucci (Venezia)

UNA REALTÀ ITALIANA GUIDATA DALLA TECNOLOGIA. DISPOSITIVI INNOVATIVI SVILUPPATI PER OTTIMIZZARE L'EFFICACIA E LA SICUREZZA: UNA REALTÀ ITALIANA GUIDATA DALLA TECNOLOGIA. Vittorio Dorrucci Azienda ULSS 12 Veneziana S.C. di Chirurgia Vascolare ed Endovascolare Dipartimento CardioToracoVascolare Direttore: Dr Vittorio Dorrucci

Carbon exists in 4 forms : diamond, graphite, glassy carbon, pyrolytic carbon (the only one used as a coating). CID has developed Bio-Inducer Surface Diamond – like carbon coating

“Physical and mechanical properties derive from richness in sp3 bonds” CID has developed Bio-Inducer Surface: Getting a faster endothelialization “Physical and mechanical properties derive from richness in sp3 bonds” The nature of pure carbon coatings depends on their closeness to the molecular structure of diamonds (sp3 bonds) The Bio Inducer Surface (≤0.3 µm) is a 2nd generation pure carbon coating that has a cristalline structure extremely close to that of diamond, with a further improvement of its bio/haemo compatibility

Pyrolytic Carbon FUNDAMENTAL CHARACTERISTICS Biocompatibility (structure similar to the chemically inert diamond) Thrombus resistance Woven elasticity similar to bony Good resistance to the friction Good solidity

Pyrolytic Carbon Biomaterials September 1995 (Vol. 16, Issue 13, Pages 973-6) Platelet and coagulation factor variations induced in vitro by polyethylene terephthalate (Dacron) coated with pyrolytic carbon. E Cenni, C R Arciola, G Ciapetti, D Granchi, L Savarino, S Stea, D,etc Biomaterials November 1995 (Vol. 16, Issue 16, Pages 1223-7) Adhesive protein expression on endothelial cells after contact in vitro with polyethylene terephthalate coated with pyrolytic carbon. E Cenni, D Granchi, C R Arciola, G Ciapetti, L Savarino, S Stea, D Journal of Materials Science Volume 16, Number 12, 1231-1238 Nitinol Carbofilm coated stents for peripheral applications: Study in the porcine model Prunotto M, Isaia C, Gatti MA J Mater Sci Mater Med. 2005 Dec;16(12):1231-8. Nitinol Carbofilm coated stents for peripheral applications: study in the porcine model. Prunotto M, Isaia C, Gatti MA, Monari E, Pasquino E, Galloni M.

Carbofilm: Key Features Enhance haemo and biocompatibility Improve tissue interaction and inhibits foreign body reaction Improve Blood Interaction: preventing clot and thrombus formation reducing local inflammatory reaction promoting a well organized layer growth improve surface endothelialization Inhibits Complement activation

The worst setting for trombotic events Sorin Carbomedics St. Jude Medtronic …others.... Pyrolitic Carbon (PyC) is the only material used to realize mechanical heart valve leaflets since almost 40 years thanks to its un-matched thrombo-resistant properties

Carbofilm: Range of Application CARBOSTENT 

Bio Inducer Surface Biocompatibility: In vivo evidence (1) Balloon Expandable Stents

Bio Inducer Surface Biocompatibility: In vivo evidence (2) Self Expanding Stents

Bio Inducer Surface is available on the entire CID stent product portfolio

Self Expanding Stents Flexibility and Conformability for SFA Cell design dedicated to SFA guarantees appropriate flexibility for optimal conformability  Adequate Radial Force for high-calcified vessels Lengths up to 150 mm to treat long lesions Radial Force and Precision for Iliac Arteries Cell architecture for an uniform radial force and excellent scaffolding Exclusive stent design for negligible foreshortening to maximize implant precision Bio Inducer Surface with its exceptional bio&haemo compatibility, seals the bulk Nitinol material (Nickel-Titanium alloy) avoiding any release of heavy metal ions.

Clinical Project: Easy Flype Registry PTA CON EasyFlype NELL’OCCLUSIONE DELL’A. FEMORALE SUPERFICIALE IN PAZIENTI “REAL WORLD” Pazienti ‘Real World’ con arteriopatia aterosclerotica sintomatica con steno-occlusione dell’arteria femorale superficiale 300 patients 12 Italian Sites* OBJECTIVE: Valutare l’efficacia nella pervietà primaria del dispositivo Easy Flype nel trattamento endovascolare dell’arteriopatia aterosclerotica in pazienti sintomatici con steno-occlusione dell’arteria femorale PRIMARY ENDPOINT: Valutare la pervietà primaria a 6 mesi e 12 mediante osservazione clinica , ABI Index ed Ecocolordoppler 6M 12M * Arezzo (Bellandi) – Bologna (Sensi) - Empoli (Credi) – Firenze (Michelagnoli) - Grosseto (Natale) – Napoli (Selvetella) – Nuoro (Fadda) – Pistoia (Sabato) – Reggio Calabria (Volpe) – Reggio Emilia (Vecchiati) – Tricase (Palasciano) – Venezia (Dorrucci)

CID and Bio Inducer Surface: New Entry Now AVAILABLE

Cre8TM BTK: distinctive features Abluminal Reservoir Technology Amphilimus™ Formulation: Sirolimus + organic acid BIS: Bio Inducer Surface

Abluminal Reservoir Technology CID utilizes a proprietary polymer-free drug release system constituted by reservoirs on the stent's outer surface. ARTERIAL WALL Drug elution is controlled and directed exclusively towards the vessel wall BLOOD FLOW Lack of any polymer Lack of any drug Co-Cr thin stent strut: 80 µm

ART: controlled and directed drug elution The Cre8™release kinetic has been defined fixing the parameters inside the Fick’s law * * Cre8 implants in rabbit model Fick’s law Peak drug tissue concentration during the first days 50% drug elution in approximately 18 days 65%-70% drug elution within 30 days Complete drug elution within 90 days

Amphilimus™ Formulation During Drug Release After Drug Release (3 months) BMS covered with Bio Inducer Surface (BIS) Pure carbon coating Excellent haemo/bio compatible features No late inflammatory stimuli inside the treated segment (Sirolimus + organic acid) CID AmphilimusTM Formulation Sustained drug elution Modulated drug bioavailability Raised homogeneous drug distribution Enhanced drug stability

Cre8TM BTK features for improved efficacy in diabetics 1) Polymer-free with controlled abluminal elution 2) Cre8 BTK employs a permeation enhancer (organic acid) in its formulation Fatty acids are used to improve transdermal and skin delivery of many different drugs. ARTERIAL WALL Drug elution is precisely controlled Cardiac fatty acid uptake is double in diabetic mice model. DICLOFENAC BLOOD FLOW Lack of any polymer Lack of any drug NO Polymer reduced inflammatory trigger Drug + Permeation enhancer Increased drug concentration

Cre8TM: Results Preclinical study in pig model 7 days FU 90 days FU BMS + BIS Cre8 = DES + BIS Cypher Moretti et al, Eurointervention 2012;7:1087-1094

Primary Endpoint: 6-month in-stent Late Lumen Loss NEXT Study Primary Endpoint: 6-month in-stent Late Lumen Loss Overall Population Diabetic subgroup P<0.0001 0.14±0.36 0.34±0.40 0.43±0.41 - 60% - 72% 0.12±0.29 P=0.0002 Cre8 (162 pts) TAXUS Liberté (161 pts) p value Diabetes 29.6% (48/162) 24.2% (39/161) 0.2735 ID Diabetes 6.2% (10/162) 6.8% (11/161) 0.8101 Non-ID Diabetes 23.5% (38/162) 17.4% (28/161) 0.1765 D. Carriè, “A Multicenter Randomized Trial Comparing Amphilimus- With Paclitaxel-Eluting Stents in De Novo Native Coronary Artery Lesions”; J. Am. Coll. Cardiol. 2012 Apr 10; 59(15): 1371-6.

Conclusions The exclusive Bio inducer Surface coating accelerates endothelization and struts coverage, reduces thrombogenity and seals against the release of heavy metal ions like nickel from Nitinol alloy; All the devices are designed to optimize efficacy and safety performances thanks to their innovative features and Abluminal Reservoir Technology and all CID Italian Technology are driven by improving clinical patients’ conditions.