PACCOCATH ISR I/II - Deb-bbraun.de

TCT 2007 - Late Breaking Studies and First Report Investigations
Wednesday, 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
Bruno Scheller
for the Paccocath ISR Study Group
Klinik für Innere Medizin III, Universitätsklinikum des
Saarlandes, Homburg / Saar, Germany

Presenter Disclosure Information
Bruno Scheller, MD
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
PACCOCATH in patients is investigational only

Presenter Disclosure Information
Bruno Scheller, MD
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
UNLABELED/UNAPPROVED USES DISCLOSURE:
PACCOCATH in patients is investigational only

Drug-Eluting Balloon (PACCOCATH)
Drug-Eluting Stent
• Slow release
• Persistent drug exposure
• ~ 100 - 200 µg dose
• Polymer
• Stent mandatory
Drug-Eluting Balloon
(PACCOCATH)
• Immediate release
• Short-lasting exposure
• ~ 300 - 600 µg dose
• No polymers
• Premounted stent optional
Circulation 2004; 110: 810-4, Heart 2007, 93: 539-41

Primary endpoint (late lumen loss in-segment)
Uncoated balloon
PACCOCATH
0.74 ± 0.86 mm 0.03 ± 0.48 mm
New Engl J Med 2006, 355: 2113-24

PACCOCATH ISR I
New Engl J Med 2006, 355: 2113-24

PACCOCATH ISR I/II
Efficacy and Safety of Paclitaxel-Coated Balloons
in Coronary In-Stent Restenosis
Homburg/Saar, Freiburg, Charité Mitte Berlin,
Charité Virchow Berlin, Mannheim-Heidelberg
• 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/II
• 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 and iopromide
(Ultravist ® )
– Uncoated balloon of the same
type (BMT, Oberpfaffenhofen)
• 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

PACCOCATH ISR I/II – Patient Characteristics
Uncoated balloon
n 54
Drug-coated balloon
Age 66.3 ± 9.8 years 65.4 ± 10.3 years 0.805
Male gender 31 (57 %) 42 (77 %) 0.125
54
p
Diabetes mellitus
Insulin-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 disease
Three-vessel disease
13 (24 %)
19 (35 %)
22 (41 %)
9 (17 %)
24 (44 %)
21 (39 %)
0.495
RCA
CX
LAD
17 (32 %)
12 (22 %)
25 (46 %)
18 (33 %)
13 (24 %)
23 (43 %)
0.611
p-values adjusted according to Fisher’s method of combining independent tests

PACCOCATH ISR I/II - Lesions
60%
50%
Patterns of ISR (Mehran classification) ISR I/II (n=108)
p=0.38
Uncoated balloon
Drug-coated balloon
40%
30%
20%
10%
0%
IA IB IC ID II III IV
p-values adjusted according to Fisher’s method of combining independent tests

PACCOCATH ISR I/II - Intervention
Uncoated balloon
n 54
Drug-coated balloon
54
p
Study balloon
Diameter
Length
3.0 ± 0.3 mm
24.3 ± 5.0 mm
3.0 ± 0.3 mm
24.1 ± 4.9 mm
1.000
0.592
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
p-values adjusted according to Fisher’s method of combining independent tests

PACCOCATH ISR I/II
Angiographic measurements at treatment
Uncoated balloon Drug-coated balloon p
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
p-values adjusted according to Fisher’s method of combining independent tests

PACCOCATH ISR I/II
Angiographic measurements at follow-up angiography
Uncoated balloon Drug-coated balloon p
n 54 54
Follow-up angiography
49 (91 %)
47 (87 %)
0.944
Minimal lumen diameter
In-stent
In-segment
1.53 ± 0.81 mm
1.50 ± 0.79 mm
2.30 ± 0.62 mm
2.23 ± 0.57 mm
0.003
0.004
Late lumen loss
In-stent
In-segment
0.81 ± 0.79 mm
0.80 ± 0.79 mm
0.14 ± 0.46 mm
0.11 ± 0.44 mm
0.001
0.001
Binary restenosis rate
In-stent
In-segment
24 (49 %)
25 (51 %)
3 (6 %)
3 (6 %)
0.001
0.001
p-values adjusted according to Fisher’s method of combining independent tests

PACCOCATH ISR I/II
24 month Clinical follow-up
Uncoated balloon Drug-coated balloon p
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 - 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. 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 Restenosis
in-segment
10 (43 %) vs. 1 (5 %)
∆ 38 %
15 (56 %) vs. 2 (7 %)
∆ 49 %
ISR I 0.002
ISR II 0.001
TLR 24 months
6 (23 %) vs. 0
∆ 23 %
14 (50 %) vs. 3 (11 %)
∆ 39 %
ISR I 0.011
ISR II 0.001
MACE 24 months
9 (35 %) vs. 1 (4 %)
∆ 31 %
16 (57 %) vs. 5 (18 %)
∆ 39 %
ISR I 0.005
ISR II 0.003

PACCOCATH ISR I vs. II
Late lumen loss in-segment
1.8
1.6
uncoated balloon
drug-coated balloon
late lumen loss in-segment [mm]
1.4
1.2
1.0
0.8
0.6
0.4
0.2
0.0
0.74
p=0.002
∆ 0.71 mm
0.03
0.83
p=0.001
∆ 0.67 mm
0.16
ISR I
ISR II

Conclusions
• First in man trial with a paclitaxel-coated balloon
(PACCOCATH
technology)
• 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.

PACCOCATH - clinical applications
• Treatment of ISR
• PACCOCATH ISR I/II
• PEPCAD II
• Small vessels
• PEPCAD I
• Bifurcation lesions
• PEPCAD V
• DEB with pre-mounted stent
• PEPCAD III
• Peripheral artery disease
• THUNDER
• PACCOCATH FEM
• Pediatric cardiology
CE mark for ‘SeQuent Please’ expected in QII 2008

PACCOCATH ISR Study Group
• 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