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