• V. Dorrucci (Venezia)

Azienda ULSS 12 Veneziana S.C. di Chirurgia Vascolare ed EndovascolareDipartimento CardioToracoVascolare Direttore: Dr Vittorio Dorrucci

DISPOSITIVI INNOVATIVI SVILUPPATI PER OTTIMIZZARE L'EFFICACIA E LA SICUREZZA:

UNA REALTÀ ITALIANA GUIDATA DALLA TECNOLOGIA.

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”

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

CID has developed Bio-Inducer Surface: Getting a faster endothelialization

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

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, 1231-1238Nitinol 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.

Pyrolytic Carbon

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

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

The worst setting for trombotic events

Sorin

St. JudeCarbomedics

Medtronic …others....

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

Bio Inducer Surface with its exceptional bio&haemo compatibility, seals the bulk Nitinol material (Nickel-Titanium alloy) avoiding any release of heavy metal ions.

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

PTA CON EasyFlype NELL’OCCLUSIONE DELL’A. FEMORALE SUPERFICIALE IN PAZIENTI “REAL WORLD”

Clinical Project: Easy Flype Registry

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)

Now AVAILABLE

CID and Bio Inducer Surface: New Entry

Cre8TM BTK: distinctive features

Abluminal Reservoir Technology

Amphilimus™ Formulation: Sirolimus + organic acid

BIS: Bio Inducer Surface

ARTERIAL WALLDrug elution is controlled and

directed exclusively towards the vessel wall

BLOOD FLOWLack of any polymer

Lack of any drug

CID utilizes a proprietary polymer-free drug release system constituted by reservoirs on the stent's outer surface.

Abluminal Reservoir Technology

Co-Cr thin stent strut: 80 µm

• 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

*

* Cre8 implants in rabbit model

The Cre8™release kinetic has been defined fixing the parameters inside the Fick’s law

ART: controlled and directed drug elution

Fick’s law

CID AmphilimusTM Formulation Sustained drug elution Modulated drug bioavailability Raised homogeneous drug

distribution Enhanced drug stability

Amphilimus™ Formulation

(Sirolimus + organic acid)

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

Cre8TM BTK features for improved efficacy in diabetics

ARTERIAL WALLDrug elution is precisely controlled

BLOOD FLOWLack of any polymer

Lack of any drug

1) Polymer-free with controlled abluminal elution

NO Polymer reduced

inflammatory trigger

2) Cre8 BTK employs a permeation enhancer (organic acid) in its formulation

Cardiac fatty acid uptake is double in diabetic mice model.

DICLOFENAC

Fatty acids are used to improve transdermal and skin delivery of many different drugs.

Drug+

Permeation enhancer

Increased drug concentration

Cre8TM: Results Preclinical study in pig model

7 days FU 90 days FU

Moretti et al, Eurointervention 2012;7:1087-1094

BMS + BIS

Cre8 = DES + BIS

Cypher

0

0,1

0,2

0,3

0,4

0,5

In-stent LLL

mm

Cre8 (148 les,141 pts)

TAXUS Liberté (145 les,135 pts)

P<0.0001

0.14±0.36

0.34±0.40

0

0,1

0,2

0,3

0,4

0,5

In-stent LLL

mm

Cre8 (42 les, 42 pts)

TAXUS Liberté (38 les, 33 pts) 0.12±0.29

0.43±0.41

P=0.0002

Diabetic subgroupOverall Population

- 72%- 60%

NEXT StudyPrimary Endpoint: 6-month in-stent Late Lumen Loss

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.