DRug Eluting Absorbable Metal Stent: dreaming the...

Symposium Biotronik High-Tech 2014

Didier Tchétché Clinique Pasteur Toulouse

DRug Eluting Absorbable Metal Stent: dreaming the future!

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Key characteristics of absorbable scaffold materials

Material PLLA1 Iron2 Magnesium

Alloy3

Tensile Strength (MPa) ~30-45 300 280

Tensile Modulus (GPa) 1.2 – 3.0 200 45

Elongation (%) 2 – 6 25 23

Total Degradation Time 2-3 Years > 4 years 9-12 months

Iron @ 28d Magnesium @ 180d

1 Ratner DB, et al. Biomaterials Science: Introduction to Materials in Medicine, 2nd Edition. Elsevier Academic Press, 2004. 2/3 Hermanwan H, et al. “Developments in metallic biodegradable stents. Acta Biometerialia. 6 (2012):1693-1697. 4 “A Cautionary Tale”, Ormiston, J., Serruys, P., et al., Circ Cardiovasc Interv 2011;4;535-538, Oct. 2011

PLLA @ 1m4

Biocompatibility

Mechanics

Absorption

Absorbable scaffolds

For coronary scaffolds, tailor-made Magnesium alloys provide the best balance

Iron @ 28d


Vascular restoration therapy: Bioabsorption of magnesium in single steps

At the beginning T = 0: Post scaffold deployment §  Drug starts to elute

§  No signs of degradation in coating or metal T = 0



Second phase T = 1 month §  Drug elutes from the polymer §  Tissue begins to grow over the strut, start of the

healing process

§  Slow hydroxylation of magnesium core into Mg-oxide

T = 1 month

Second phase



T = 3 months

Third phase T = 3 months §  Drug elution is completed §  Magnesium is further converted to Mg-oxide and

bioabsorption begins §  Struts are fully covered with tissue



T = 9 months §  Magnesium core is fully converted into Mg-oxide.

Bioabsorption of Mg-oxide is ongoing §  Material begins to disassociate and smooth muscle

cells infiltrate through the struts

T = 9 months

Fourth phase



T = 1 year §  Most of the scaffold material has been bioabsorbed

T = 1 year

Fifth phase



T = 1.5 years §  All foreign material is gone, only cells are left

§  Vessel has returned to its natural, healed state

T = 1.5 years

Completed

9 DREAMS Device Overview March 2013

From bare AMS to first and second generation DREAMS

AMS

165µm 80µm

28 day animal study

No drug elu8on

DREAMS G1

120µm

90 day animal study

Paclitaxel + PLGA

(2010)


Device success 100% (47 / 47)

Procedure success 100% (46 / 46)

Clinical results 6-month1 12-months1 24-months Cohort 1 & 2 Cohort 1 & 2 Cohort 1&2

TLF 4.3% (2/46) 6.8% (3/44) 6.8% (3/44)

Cardiac death 0.0% 0.0% (0/44) 0.0% (0/44)

MI2 0.0% 2.3% (1/44) 2.3% (1/44)

Scaffold thrombosis 0.0% 0.0% (0/44) 0.0% (0/44)

TLR (clinically driven)3 4.3% (2/46) 4.5% (2/44) 4.5% (2/44)

Six to 24-month clinical follow-up

1 DREAMS was implanted in the OM and the MI occurred in the LCx. 2 Both pts had angina, 1 pt received an additional DREAMS in the target lesion during the initial procedure because of a flow-limiting bailout.

Device Success: successful delivery, deployment, removal of delivery system after release of the scaffold. Safe removal of the device in case of deployment failure. Procedure Success: device success and attainment of a final residual stenosis of < 50%, absence of a MACE during hospital stay to 7 days.

M Haude, et al. The Lancet 15 January 2013.


6-and 12-month late lumen loss (LLL) Cum

ulat

ive

Freq

uenc

y (%

)

In-Scaffold LLL (mm)

0

20

40

60

80

100

-0.40 -0.20 0.00 0.20 0.40 0.60 0.80 1.00 1.20 1.40 1.60 1.80

6-month follow-up 12-month follow-up

12-month LLL 0.52 ± 0.39 mm

6-month LLL 0.64 ± 0.50 mm

M Haude, et al. The Lancet 15 January 2013.

PROGRESS-AMS

LLL 4 months: 1.08 ±0.49mm


ACH concentra8on Low: 0.36 µg/mL Medium: 3.6 µg/mL High: 18 µg/mL Nitro concentra8on 200 µg/mL

NTG

Mean ±SD

-‐4.15 ±9.94%

8.13 ± 10.49%

-‐7.71 ± 7.44%

8.92 ±9.91%

-‐11.82 ±13.97%

-‐10.82 ±16.58%

Proximal Segment Scaffolded Segment Distal Segment

Rela8v

e Ch

ange in m

ean lumen

diameter %

ACH NTG ACH NTG ACH -‐ 80

-‐ 60

-‐ 40

-‐ 20

0

20

40

60

BIOSOLVE-I study results Vasomotion results at 12-month (N=18)


Also demonstrates Restoration of Natural Vessel Angulation

Change in vessel angulations at 6 months

Post 6 Mo FUP

Pre-Procedure Post-Procedure 6-month FUP

Pre-Procedure N=47

Post-Procedure N=47

6-Month FUP N=36

Lesion Angulation (°) 31.38 ± 21.23 14.89 ± 12.00 26.11 ± 15.91

60° 15° 60°

Source: Koolen J. et al; Poster Presentation, TCT 2011

Post procedure 12Mo FUP

SideB SideB

GWS

GWS

Ca Ca

**

*

*

Garcia-Garcia HM et al. Work in progress.

OCT measurements for BIOSOLVE Struts fade as evidence of bioabsorption

15 DREAMS Device Overview March 2013

DREAMS G1

120µm

90 day animal study

Paclitaxel + PLGA

DREAMS G2

150µm

Sirolimus + PLLA (BIOlute)

90 day animal study

Clinical study started in Oct-‐2013

From bare AMS to first and second generation DREAMS – DRug-Eluting Absorbable Metal Scaffold

16

DREAMS; crimped (3.0mm nominal)

Expansion to 3.0mm

Expansion to 5.4mm

New scaffold design and process allow for improved scaffold expansion

Occurrence probability of 2nd fracture

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

3.0 3.3 3.5 3.8 4.0 4.3 4.5 4.8 5.0 5.3 5.5

Fracture Diameter [mm]

Occ

uren

ce P

roba

bilit

y

AMS-3.0 S

AMS-4.0 S

§ One double marker per scaffold end

§ Composite marker with fine Tantalum powder and silicone matrix

Initiation of first

fractures 1st gen

Initiation of first

fractures 2nd gen

Occurrence probability of fractures

DREAMS 1st generation

DREAMS 2nd generation

RFD: (rated

fracture diameter*):

4.87mm

* RFD= Rated fracture diameter with 99% probability and 95% confidence interval, N=316


Potential for side branch access

Kissing balloon inflation: MB 3.0 mm / SB 2.5 mm

D = 1.3mm

5.5mm

*Experimental, N=1

Experimental* post-dilatation of DREAMS G2 shows potential side-branch access


Coating integrity of DREAMS G2

SEM images of expanded 3.0 mm DREAMS G2 (expansion diameter 3.5 mm)

SEM images of expanded 3.0 mm DREAMS G2 (expansion diameter 4.25 mm)


Conclusion: what could be the future?

§  Decent degradation time

§  Restoration of vessel integrity and vasomotion

§  Effective eluted drug

§  All comers (bifurcation, tortuosity…)?

§  Minimized inflammation

§  Safety and low TLF rate


THANK YOU

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