1. Bruno Scheller for the Paccocath ISR Study Group
TCT Late Breaking Studies and First Report Investigations Wednesday, October , 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

2. Drug-Eluting Balloon (DEB)
Drug-Eluting Stent
Slow release
Persistent drug exposure
~ µg dose
Polymer
Stent mandatory
Drug-Eluting Balloon
Immediate release
Short-lasting exposure
~ µg dose
No polymers
Premounted stent optional
Heart 2007, 93:

3. Paccocath ISR I/II Two trials Paccocath ISR I Paccocath ISR 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

4. Paccocath ISR I/II Primary endpoint Main inclusion criteria
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
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)

5. Paccocath ISR I/II – Patient Characteristics Single-vessel disease
Uncoated balloon
Drug-coated balloon p n 54
Age
66.3 ± 9.8 years
65.4 ± 10.3 years
0.805
Male gender
31 (57 %)
42 (77 %)
0.125
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 %
0.866
Unstable angina
41 %
37 %
1.000
Single-vessel disease
Two-vessel disease
Three-vessel disease
13 (24 %)
19 (35 %)
22 (41 %)
24 (44 %)
21 (39 %)
0.495
RCA CX
LAD
17 (32 %)
12 (22 %)
25 (46 %)
18 (33 %)
23 (43 %)
0.611
p-values adjusted according to Fisher’s method of combining independent tests

6. Paccocath ISR I/II - Lesions
p-values adjusted according to Fisher’s method of combining independent tests

7. Paccocath ISR I/II - Intervention
Uncoated balloon
Drug-coated balloon p n 54
Study balloon
Diameter
Length
3.0 ± 0.3 mm
24.3 ± 5.0 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 %)
Additional stents
3 (6 %)
GP IIb/IIIa antagonists
7 (13 %)
5 (9 %)
p-values adjusted according to Fisher’s method of combining independent tests

8. Paccocath ISR I/II Angiographic measurements at treatment
Uncoated balloon
Drug-coated balloon p n 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

9. Paccocath ISR I/II Angiographic measurements at follow-up angiography
Uncoated balloon
Drug-coated balloon p n 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
0.81 ± 0.79 mm
0.80 ± 0.79 mm
0.14 ± 0.46 mm
0.11 ± 0.44 mm
0.001
Binary restenosis rate
24 (49 %)
25 (51 %)
3 (6 %)
p-values adjusted according to Fisher’s method of combining independent tests

10. 24 month Clinical follow-up Myocardial infarction
Paccocath ISR I/II
24 month Clinical follow-up
Uncoated balloon
Drug-coated balloon p n 54
TLR
20 (37 %)
3 (6 %)
0.001
Myocardial infarction
5 (9 %)
1 (2 %)
0.577
Death
2 (4 %)
0.912
Stroke
0.840
MACE
25 (46 %)
6 (11 %)
Intention-to-treat analysis; p-values adjusted according to Fisher’s method of combining independent tests

11. 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

12. Paccocath ISR I vs. II ISR I ISR II p n 52 56 Age 63.6 ± 10.8 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
MACE 24 months
9 (35 %) vs. 1 (4 %)
∆ 31 %
16 (57 %) vs. 5 (18 %)
ISR I 0.005
ISR II 0.003

13. Late lumen loss in-segment
Paccocath ISR I vs. II
Late lumen loss in-segment

14. Conclusions 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.

15. DEB - 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

16. 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
Bayer-Schering Pharma AG, Berlin