2UNA REALTÀ ITALIANA GUIDATA DALLA TECNOLOGIA. DISPOSITIVI INNOVATIVI SVILUPPATI PER OTTIMIZZARE L'EFFICACIA E LA SICUREZZA:UNA REALTÀ ITALIANA GUIDATA DALLA TECNOLOGIA.Vittorio DorrucciAzienda ULSS 12 Veneziana S.C. di Chirurgia Vascolare ed EndovascolareDipartimento CardioToracoVascolare Direttore: Dr Vittorio Dorrucci
3Carbon exists in 4 forms : diamond, graphite, glassy carbon, pyrolytic carbon (the only one used as a coating).CID has developed Bio-Inducer SurfaceDiamond – like carbon coating
4“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
5Pyrolytic Carbon FUNDAMENTAL CHARACTERISTICS Biocompatibility (structure similar to the chemically inert diamond)Thrombus resistanceWoven elasticity similar to bonyGood resistance to the frictionGood solidity
6Pyrolytic CarbonBiomaterials 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,etcBiomaterials November 1995 (Vol. 16, Issue 16, Pages )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, DJournal of Materials Science Volume 16, Number 12,Nitinol Carbofilm coated stents for peripheral applications: Study in the porcine modelPrunotto M, Isaia C, Gatti MAJ Mater Sci Mater Med Dec;16(12):Nitinol Carbofilm coated stents for peripheral applications: study in the porcine model.Prunotto M, Isaia C, Gatti MA, Monari E, Pasquino E, Galloni M.
7Carbofilm: Key Features Enhance haemo and biocompatibilityImprove tissue interaction and inhibits foreign body reactionImprove Blood Interaction:preventing clot and thrombus formationreducing local inflammatory reactionpromoting a well organized layer growthimprove surface endothelializationInhibits Complement activation
8The worst setting for trombotic events SorinCarbomedicsSt. JudeMedtronic…others....Pyrolitic Carbon (PyC) is the only material used to realize mechanical heart valve leaflets since almost 40 years thanks to its un-matchedthrombo-resistant properties
10Bio Inducer Surface Biocompatibility: In vivo evidence (1) Balloon Expandable Stents
11Bio Inducer Surface Biocompatibility: In vivo evidence (2) Self Expanding Stents
12Bio Inducer Surface is available on the entire CID stent product portfolio
13Self Expanding Stents Flexibility and Conformability for SFA Cell design dedicated to SFA guarantees appropriate flexibility for optimal conformability Adequate Radial Force for high-calcified vesselsLengths up to 150 mm to treat long lesionsRadial Force and Precision for Iliac ArteriesCell architecture for an uniform radial force and excellent scaffoldingExclusive stent design for negligible foreshortening to maximize implant precisionBio Inducer Surface with its exceptional bio&haemo compatibility, seals the bulk Nitinol material (Nickel-Titanium alloy) avoiding any release of heavy metal ions.
14Clinical 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 superficiale300 patients12 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 femoralePRIMARY ENDPOINT: Valutare la pervietà primaria a 6 mesi e 12 mediante osservazione clinica , ABI Index ed Ecocolordoppler6M12M* 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)
15CID and Bio Inducer Surface: New Entry Now AVAILABLE
16Cre8TM BTK: distinctive features Abluminal Reservoir TechnologyAmphilimus™ Formulation: Sirolimus + organic acidBIS: Bio Inducer Surface
17Abluminal Reservoir Technology CID utilizes a proprietary polymer-free drug release system constituted by reservoirs on the stent's outer surface.ARTERIAL WALLDrug elution is controlled and directed exclusively towards the vessel wallBLOOD FLOWLack of any polymerLack of any drugCo-Cr thin stent strut: 80 µm
18ART: controlled and directed drug elution The Cre8™release kinetic has been defined fixing the parameters inside the Fick’s law** Cre8 implants in rabbit modelFick’s lawPeak drug tissue concentration during the first days50% drug elution in approximately 18 days65%-70% drug elution within 30 daysComplete drug elution within 90 days
19Amphilimus™ Formulation During Drug ReleaseAfter Drug Release (3 months)BMS covered withBio Inducer Surface (BIS)Pure carbon coatingExcellent haemo/bio compatible featuresNo late inflammatory stimuli inside the treated segment(Sirolimus + organic acid)CID AmphilimusTM FormulationSustained drug elutionModulated drug bioavailabilityRaised homogeneous drug distributionEnhanced drug stability
20Cre8TM BTK features for improved efficacy in diabetics 1) Polymer-free with controlled abluminal elution2) Cre8 BTK employs a permeation enhancer (organic acid) in its formulationFatty acids are used to improve transdermal and skin delivery of many different drugs.ARTERIAL WALLDrug elution is precisely controlledCardiac fatty acid uptake is double in diabetic mice model.DICLOFENACBLOOD FLOWLack of any polymerLack of any drugNO Polymerreduced inflammatory triggerDrug+Permeation enhancerIncreased drug concentration
21Cre8TM: Results Preclinical study in pig model 7 days FU90 days FUBMS + BISCre8 = DES + BISCypherMoretti et al, Eurointervention 2012;7:
22Primary Endpoint: 6-month in-stent Late Lumen Loss NEXT StudyPrimary Endpoint: 6-month in-stent Late Lumen LossOverall PopulationDiabetic subgroupP<0.00010.14±0.360.34±0.400.43±0.41- 60%- 72%0.12±0.29P=0.0002Cre8(162 pts)TAXUS Liberté(161 pts)p valueDiabetes29.6% (48/162)24.2% (39/161)0.2735ID Diabetes6.2% (10/162)6.8% (11/161)0.8101Non-ID Diabetes23.5% (38/162)17.4% (28/161)0.1765D. Carriè, “A Multicenter Randomized Trial Comparing Amphilimus- With Paclitaxel-Eluting Stents in De Novo Native Coronary Artery Lesions”; J. Am. Coll. Cardiol Apr 10; 59(15):
23ConclusionsThe 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.