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Klinikum Rosenheim Department of Diagnostic and Interventional Radiology
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Gunnar Tepe
PTA
Approaches to reduce restenosis
Local Drug Delivery Basic Principles
Stent based
Short time contact
To be modified
Stent design (homogenoius delivery) Delivery kinetic „Coating/Adsorption“ Drug
Mode of delivery (with a balloon, fluid) Adjuncts Drug
Limitations of current techniques in the SFA: High restenosis rate
(better with stents, but still high)
Clinical goal (in Rutherford up to 3) 1. Increase of walking distance
2. Less TLR
Based on long-term patency
SFA
Short time local drug contact:
…the alternative
approach
Failure:
Some DCBs Work, others Do NOT Data from prospective randomized trials
7
TLR at 2 years
Indication Study Formulation DCB POB
A TAXUS Coronary ISR
Paccocath ISR I & II1,2 Paclitaxel + Iopromide
4% 37% PEPCAD II3* 6% 15%
SFA THUNDER4 15% 52% FemPac5 13% 50%
TLR at 9 months
Indication Study Study Flaw DCB TAXUS CYPHER
Small Vessel CAD Piccoleto6* Paclitaxel Alone 32% 10%
DeNovo CAD PEPCAD III7 DCB w/Pre-crimped stent
vs DES 11% 5%
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Success:
Each DEB is different
8
Contresy by Mc Fadden
Device 1
Device 2
Device 3
Same Drug, Different Additives
DCB Companies and Products
DEB Brand
IN.PACT balloons
SeQuent Please Cotavance Pantera Lux
DIOR II
Elutax Lutonix
CE CE CE - CE CE -
Manu-facturer
Medtronic-Invatec B.Braun Bayer-
Medrad Biotronik Eurocor Aachen-Resonance Lutonix
Coating Name FreePac No name No name No name No name No name No name
Drug Paclitaxel Paclitaxel Paclitaxel Paclitaxel Paclitaxel Paclitaxel Paclitaxel
Drug Carrier (Type)
Urea (Molecule
Spacer)
Iopromide (Contrast
Media)
Ultravist 370 (Contrast
Media)
BTHC (Contrast
Media Analog)
Shellac (Resin) None Unknown
Randomized data
DCB companies and products
0.035” System 0.018” 0.014” COOK Advance 18PTX
Medrad Cotavance in development
Eurocor Freeway 35 Freeway 14 (CE)
Aachen Resonance Elutax*
Lutonix Moxy
Cardionovum LegFlow
Caliber Therapeutics TADD
Biotronik Passeo 18 Lux
Medtronic Invatec IN.PACT Admiral IN.PACT Pacific IN.PACT Amphirion
Study types
1.! Proof that the DEB is safe and effective (DEB vs bare balloon)
2.! New indications a) SFA - In stent restenosis b) SFA - With stents c) SFA - with atherectomy d) BTK e) AV-Fistula
Paccocath – Cotavance technology (Thunder, FemPac trial)
Lutonix – Levant 1
3.! For US approval (DEB vs bare balloon)
Proof of concept in PVD
Study Status
COOK Advance 18 100 randomized finished+ 50 additional patients (started)
Medrad Thunder, Fempac 2 positive trials, published (n=90+90)
Eurocor Freeride n=240 patients, starting soon
Aachen Resonance unknown
Lutonix Levant I positive (n=100)
Biotronik Biolux trial n= 60 (34/60)
Medtronic Invatec SFA I n=150 (150/150)
THUNDER: OUTCOMES 6 Month Angio POBA (n=48) DCB (n=41) P
Late Lumen Loss , mm 1.7 ± 1.8 0.4 ± 1.2 < 0.001
RVD, mm 4.9 ± 0.6 5.1 ± 0.6 0.05
MLD, mm 2.8 ± 1.9 4.1 ± 1.4 0.001
Binary Restenosis (%) 44 17 0.01
TLR POBA (n=54) DCB (n=48) P
6 Month (%) 37 4 <0.001
12 Month (%) 48 10 <0.001
24 Month (%) 52 15 <0.001
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Therapy with Paccocath and
uncoated balloon
+
Patient treated with Paccocath
56 years old male patient, occlusion 11cm diabetic, smoker, hypertension, hypercholesterolemia,
Rutherford class 4
Intervention August, 2004 2 paclitaxel-coated balloons; 5 x 100 mm and 4 x 40 mm
March, 2005
March, 2006
Subgroup n, control/ n, DCB
LLL (mm) Control minus
DCB
LLL (%) DCB/
Control
Diabetes 21/14 1.2 33 Restenotic lesion 14/12 1.5 21 Calcification 18/16 1.2 25 > 10 cm 5/8 1.3 50 Pop. involvement 13/11 1.5 29
Group n=129
Control
[mm]
Paclitaxel on balloon
[mm]
Control minus paclitaxel on balloon
[mm] Total 1.7±1.8 0.4±1.2 1.3
Thunder: Subgroups
DCB: Large benefit in all subgroups
Late lumen loss (mm of diameter) 6 month post PTA
FemPac: OUTCOMES
6 Month Angio POBA (n=48) DCB (n=41) P
Late Lumen Loss , mm 0.8 0.3 0.031
RVD, mm 5.1 5.2 0.62
MLD, mm 2.7 3.6 0.037
Binary Restenosis (%) 47 19 0.035
TLR POBA (n=54) DCB (n=48) P
6 Months (%) 33 7 0.002
18-24 Months (%) 50 13 0.001
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Levent I Trial
Levent I Trial
Levent I Trial
Lesions Learnt
DEB:
- Many DEBs available, but different - Paccocath and Lutonix with positive data - Several trials under the way - learn more about indications and limitations - clinical endpoints in bigger studies
Limitations of current techniques in the BTK: 1. Technical success rate
(not addressed by drug eltuing technology) 2. High restenosis rate
(also high with bare stents)
Clinical goal (in Rutherford 5 and 6) 1. Wound heeling, prevention of amputation
2. Less TLR (?)
BTK
BTK DES vs. uncoated stents or
POPA DEBS
Destiny Trial
Presented by Bosiers et al. VEITH November 2010
Destiny Trial
Presented by Bosiers et al. VEITH November 2010
In.Pact Amphirion in BTK
Presented by Schmidt et al. LINC January 2011
In.Pact Amphirion in BTK
Presented by Schmidt et al. LINC January 2011
Lesions Learnt
1.! DES (Cypher, Xience V) reduce restenosis and TLR rates
2.! Endovascular therapy reduces the amputation rate
3.! DES until now failed to show an impact on amputation rates
4.! DEBs seem to reduce the RS rate – prospective studies pending
Further indications
Indication Name
COOK - -
Medrad
In-stent RS SFA BTK BTK
Atherectomy (+EV3)
COPA COBANA (0/70) 6 mo DSA Euro Canal US Canal
Definitve AR (0/100) 12 mo LLL
Eurocor + Stent ?In-stent RS BTK?
Freeway (ca. x/260) in discussion
Aachen Resonance ?In-stent RS? -
Lutonix - -
Biotronik - -
Medtronic Invatec In-stent RS SFA
BTK Shunt
FAIR (23/118) 6 mo DUS In Pact Deep (140/357) 12 Mo DSA + clinical Inpact Shunt (0/136) 6 mo LLL
Possible Limitation of DEBs
+ additive therapies +alternative therapies
Thunder and FemPac A luck shot
The issue of calcification
The issue of calcification
Alternative treatment
+ Turbohawk
The issue of calcification
!
!
!
!
!
!
An Ideal Combination Therapy? Atherectomy + DCB
The future of DEBs
!.is great,
But we have to learn much more +
Further studies are mandatory
Race to the US market
Not easy to be quick: FDA reqirements
Race to the US market
Use the Thunder and FemPac Data Indepented US trial planned (River Trial)
Levant II is planned based on Levant I
SFA II is planned using SFA I