Download ppt - Presenter Disclosure Information DISCLOSURE INFORMATION: The following relationship exists related to this presentation: Coinventor of a patent application

Presenter Disclosure Information

DISCLOSURE INFORMATION:The following relationship exists related to this presentation:Coinventor of a patent application for various methods of restenosis inhibition, including the technique employed in this trial, by Charité University Hospital, Berlin

Bruno Scheller, MD

UNLABELED/UNAPPROVED USES DISCLOSURE:PACCOCATH, Sequent Please and DEBlue in patients is investigational only

Bruno Schellerfor the Paccocath ISR Study Group

TCT 2007 - Late Breaking Studies and First Report InvestigationsWednesday, October 24 2007, Main area

PACCOCATH ISR 1 and 2: A Prospective, Randomized Trial of a Paclitaxel-Eluting Balloon in In-Stent

Restenosis: 2-Year Results

Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg / Saar, Germany

Heart 2007, 93: 539-41

Drug-Eluting Balloon (DEB)Drug-Eluting Balloon (DEB)

Drug-Eluting Stent• Slow release • Persistent drug

exposure• ~ 100 - 200 µg dose• Polymer• Stent mandatory

Drug-Eluting Balloon

• Immediate release• Short-lasting exposure• ~ 300 - 600 µg dose• No polymers• Premounted stent

optional

New Engl J Med 2006, 355: 2113-24

Uncoated balloon Coated balloon

0.74 ± 0.86 mm 0.03 ± 0.48 mm

52 patientsPrimary endpoint (late lumen loss in-segment)

Paccocath ISR IPaccocath ISR I

New Engl J Med 2006, 355: 2113-24

• Two trials–separately randomized–double-blind, multicenter–identical protocol–108 patients in total

• Paccocath ISR I–52 patients

• Paccocath ISR II–56 patients

Paccocath ISR I/IIPaccocath ISR I/IIEfficacy and Safety of Paclitaxel-Coated Balloons

in Coronary In-Stent Restenosis

Homburg/Saar, Freiburg, Charité Mitte Berlin,

Charité Virchow Berlin, Mannheim-Heidelberg

• Main inclusion criteria– Clinically relevant coronary ISR

– Diameter stenosis > 70 %

– Lesion length < 30 mm

– Vessel diameter 2.5 to 3.5 mm

• Repeated PTCA of coronary

ISR – Coated balloon with 3 µg

paclitaxel / mm² balloon surface

– Uncoated balloon of the same type (BMT, Oberpfaffenhofen)

Paccocath ISR I/IIPaccocath ISR I/II

• Primary endpoint– In-segment late lumen loss after 6

months

– Independent, blinded angiographic core lab

• U. Dietz, Wiesbaden

• Secondary endpoints– Binary restenosis rate, MACE

• Statistics– p-values adjusted according to

Fisher’s method of combining independent tests

• ASA + clopidogrel– 4 weeks in both groups

Uncoated balloon Drug-coated balloon p

n 54 54

Age 66.3 ± 9.8 years 65.4 ± 10.3 years 0.805

Male gender 31 (57 %) 42 (77 %) 0.125

Diabetes mellitusInsulin-dependent

11 (20 %)6 (11%)

9 (17 %)3 (6 %)

0.313

Hyperlipidema 72 % 78 % 0.485

Smoking 48 % 43 % 0.772

Hypertension 82 % 82 % 0.866

Unstable angina 41 % 37 % 1.000

Single-vessel disease

Two-vessel diseaseThree-vessel disease

13 (24 %)19 (35 %)22 (41 %)

9 (17 %)24 (44 %)21 (39 %)

0.495

RCACX

LAD

17 (32 %)12 (22 %)25 (46 %)

18 (33 %)13 (24 %)23 (43 %)

0.611

Paccocath ISR I/II – Patient CharacteristicsPaccocath ISR I/II – Patient Characteristics

p-values adjusted according to Fisher’s method of combining independent tests

0%

10%

20%

30%

40%

50%

60%

IA IB IC ID II III IV

Uncoated balloon

Drug-coated balloon

Patterns of ISR (Mehran classification) ISR I/II (n=108)

p=0.38

Paccocath ISR I/II - LesionsPaccocath ISR I/II - Lesions



n 54 54

Study balloonDiameterLength

3.0 ± 0.3 mm24.3 ± 5.0 mm

3.0 ± 0.3 mm24.1 ± 4.9 mm

1.0000.592

Mean pressure 12.7 ± 2.7 atm 12.5 ± 2.6 atm 0.819

Balloon inflation time 68.9 ± 37.7 sec 77.2 ± 42.2 sec 0.063

Paclitaxel residue on balloon post-angioplasty

- 4.2 ± 4.1% (ISR I)

Restenotic DES 2 (4 %) 2 (4 %) 1.000

Additional stents 2 (4 %) 3 (6 %) 1.000

GP IIb/IIIa antagonists 7 (13 %) 5 (9 %) 1.000

Paccocath ISR I/II - InterventionPaccocath ISR I/II - Intervention


Angiographic measurements at treatmentAngiographic measurements at treatment



n 54 54

Left ventricular function 60.3 ± 13.9 % 60.8 ± 14.5 % 0.862

Lesion length 18.6 ± 8.3 mm 18.3 ± 9.7 mm 0.845

Reference diameter 2.94 ± 0.37 mm 2.94 ± 0.35 mm 0.731

Minimal lumen diameter initial 0.70 ± 0.35 mm 0.63 ± 0.29 mm 0.015

Minimal lumen diameter post angioplasty

2.34 ± 0.44 mm 2.43 ± 0.47 mm 0.955


Angiographic measurements at follow-up angiographyAngiographic measurements at follow-up angiography



n 54 54

Follow-up angiography 49 (91 %) 47 (87 %) 0.944

Minimal lumen diameter In-stent

In-segment1.53 ± 0.81 mm1.50 ± 0.79 mm

2.30 ± 0.62 mm2.23 ± 0.57 mm

0.0030.004

Late lumen lossIn-stent

In-segment0.81 ± 0.79 mm0.80 ± 0.79 mm

0.14 ± 0.46 mm0.11 ± 0.44 mm

0.0010.001

Binary restenosis rateIn-stent

In-segment24 (49 %)25 (51 %)

3 (6 %)3 (6 %)

0.0010.001


24 month Clinical follow-up24 month Clinical follow-up



n 54 54

TLR 20 (37 %) 3 (6 %) 0.001

Myocardial infarction 5 (9 %) 1 (2 %) 0.577

Death 3 (6 %) 2 (4 %) 0.912

Stroke 3 (6 %) 2 (4 %) 0.840

MACE 25 (46 %) 6 (11 %) 0.001

Intention-to-treat analysis; p-values adjusted according to Fisher’s method of combining independent tests

Paccocath ISR I/II - MACEPaccocath ISR I/II - MACE

TLR, MI, acute/subacute closure, stroke,

or death

Mantel-Cox log-rank test; p-values adjusted according to Fisher’s method of combining independent tests

Paccocath ISR I vs. IIPaccocath ISR I vs. II

ISR I ISR II p

n 52 56

Age 63.6 ± 10.8 years 68.0 ± 8.9 years 0.021

Female patients 15 (29 %) 20 (36 %) 0.289

Diabetes mellitus 10 (19 %) 18 (32 %) 0.095

Lesion length 18.0 ± 7.0 mm 18.8 ± 10.5 mm 0.669

Binary Restenosisin-segment

10 (43 %) vs. 1 (5 %)

∆ 38 %

15 (56 %) vs. 2 (7 %)

∆ 49 %ISR I 0.002ISR II 0.001

TLR 24 months6 (23 %) vs. 0

∆ 23 %

14 (50 %) vs. 3 (11 %)

∆ 39 %ISR I 0.011ISR II 0.001

MACE 24 months9 (35 %) vs. 1 (4 %)

∆ 31 %

16 (57 %) vs. 5 (18 %)

∆ 39 %ISR I 0.005ISR II 0.003

Paccocath ISR I vs. IIPaccocath ISR I vs. II

0.74

0.83

0.03

0.16

0.0

0.2

0.4

0.6

0.8

1.0

1.2

1.4

1.6

1.8

ISR I ISR II

late

lum

en lo

ss in

-seg

men

t [m

m]

uncoated balloon drug-coated balloon

p=0.002∆ 0.71 mm

p=0.001∆ 0.67 mm

Late lumen loss in-segmentLate lumen loss in-segment

• First in man trial with a paclitaxel-coated balloon

• Angiographic and clinical efficacy up to 24 months

• Safety 24 months

• no late thrombosis

• clopidogrel only for one month

• No coating-related adverse events

• Inhibition of restenosis by drug-coated balloons does not

require stent implantation and sustained drug release at

the site of injury.

ConclusionsConclusions

DEB - clinical applicationsDEB - clinical applications

• Treatment of ISR• Paccocath ISR I/II• PEPCAD II

• Small vessels• PEPCD I

• Bifurcation lesions• PEPCAD V

• DEB with pre-mounted stent• PEPCAD III

• Peripheral artery disease• THUNDER• PACCOCATH FEM

• Pediatric cardiology

• Study centers• Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes, Homburg/Saar

(M. Böhm, B. Cremers, M. Kindermann, U. Laufs, T. Müller, B. Scheller, J. Schmidt, S. Siaplaouras; N. Hollinger, B. Werner)

• Innere Medizin III, Medizinische Universitätsklinik, Freiburg i. Br. (Christoph Hehrlein; A. Becherer)

• Kardiologie, Campus Virchow-Klinikum, Charité, Berlin (Wolfgang Bocksch, J. Waigand)

• Kardiologie, Campus Mitte, Charité, Berlin (Wolfgang Rutsch; S. Schroeckh)

• I. Medizinische Klinik, Universitätsklinikum, Mannheim-Heidelberg (Dariush Haghi, K. Haase, T. Süsselbeck)

• Angiographic Core Lab• Deutsche Klinik für Diagnostik, Wiesbaden (Ulrich Dietz, K. Wilhelmi; Quantitative

Coronary Angiography)

• Pharmaceutical Development• Ulrich Speck; Charité, Berlin

• Devices and Sponsoring• Bavaria Medizin Technologie, Oberpfaffenhofen• Bayer-Schering Pharma AG, Berlin

Paccocath ISR Study GroupPaccocath ISR Study Group