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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
p-values adjusted according to Fisher’s method of combining independent tests
Uncoated balloon Drug-coated balloon p
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
p-values adjusted according to Fisher’s method of combining independent tests
Angiographic measurements at treatmentAngiographic measurements at treatment
Paccocath ISR I/IIPaccocath ISR I/II
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
Angiographic measurements at follow-up angiographyAngiographic measurements at follow-up angiography
Paccocath ISR I/IIPaccocath ISR I/II
Uncoated balloon Drug-coated balloon p
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
p-values adjusted according to Fisher’s method of combining independent tests
24 month Clinical follow-up24 month Clinical follow-up
Paccocath ISR I/IIPaccocath ISR I/II
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 - 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
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