Drug-Eluting Balloons

Transcription

1 TCT 2007 Sunday October , Room 152B Innovative Devices and Futuristic Concepts II: Non-Stent-Based Technologies Drug-Eluting Balloons Overview of Paclitaxel-Eluting Balloons to Prevent (And Treat) Restenosis: Experimental Findings, Device Characteristics, Clinical Experiences, and Preview of the Upcoming Late Breaking Registry Reports Bruno Scheller Klinik für Innere Medizin III, Universitätsklinikum des Saarlandes Homburg / Saar, Germany

2 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, SeQuent Please and DEBlue in patients is investigational only

3 Drug-Eluting Stents DES Hwang, Circulation 2001; 104: 600-5

4 X-ray contrast media for local drug delivery Paclitaxel in iopromide (Ultravist ) saline control Iopromide Paclitaxel 1.46 µm 60 min Iopromide Paclitaxel 14.6 µm 60 min Iopromide Paclitaxel 14.6 µm 10 min Iopromide Paclitaxel 14.6 µm 3 min * p<0.05 compared to control * * * day 0 day 3 day 6 day 9 day 12 cell density / cm² paclitaxel tissue concentration [µmol/l] tissue levels 15 min after intracoronary injection of iopromide paclitaxel or Taxol, stent implantation in LAD und CX, 15 pigs Io P ac 16 µmol (200 µm, 80ml) Io Pac 8 µmol (100 µm, 80ml) Taxol 14 µmol (10ml) Invest Radiol 2002; 37: 29-34, Eur Heart J 2003; 24: , J Am Coll Cardiol 2003; 42:

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

6 DEB + stent - porcine coronary model 28 days follow-up, n=40 no iopromide PACCOCATH technology Circulation 2004; 110: 810-4

7 DEB + stent vs. Cypher Stent Porcine coronary model, paclitaxel 3 µg/mm², 28 days Follow-up, n= p-werte * vs Kontrolle ** Paccocath vs Cypher Neointimafläche [mm²] p=0.001* p=0.004** p=0.013* 1 0 Kontrolle Paccocath Cypher Speck, Radiology 2006; 240: 411-8

8 Overdosing and Balloon Inflation Time Paclitaxel 5 µg/mm², 28 days follow-up, n= [mm²] ns p=0.001 control DEB 10s DEB 60s DEB 2x 60s 5 2x DEB 60s 4 3 p= vessel area luminal area neointimal area Cremers 2007, submitted

9 PACCOCATH Efficacy versus paclitaxel dose / mm² balloon surface %inhibition of neointimal area ,5 5,0 10,0 3,0 1,3 1,0 2,0 3,0 4,0 5,0 6,0 7,0 8,0 9,0 10,0 µg paclitaxel / mm² balloon surface

10 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:

11 PACCOCATH ISR I N Engl J Med 2006; 355:

12 PACCOCATH ISR I ISR DEB (PACCOCATH) 33 months later

13 PACCOCATH ISR I/II MACE 12-month follow-up, n=108 TLR, MI, acute/subacute closure, stroke, or death AHA November 13, 2006; Mantel-Cox log-rank test; p-values adjusted according to Fisher s method of combining independent tests

14 THUNDER trial PACCOCATH in peripheral arteries Local Taxan with short time contact for reduction of restenosis in distal arteries Binary restenosis rate at 6 month visit, n=154 60% 55% binary restenosis rate [%] 50% 40% 30% 20% 10% 44% p= % 0% control Paccocath Paclitaxel in CM Tepe, late breaking trials, TCT 2006

15 THUNDER trial PACCOCATH in peripheral arteries Tuesday, October , Main area Late Breaking Studies and First Report Investigations 1:26 pm - THUNDER: A Prospective, Randomized Trial of a Paclitaxel-Eluting Balloon, Intra-Arterial Paclitaxel, and Control in SFA Lesion: 1-Year Angiographic and Clinical Results Gunnar Tepe 1:38 pm - Critical Appraisal of the THUNDER Trial Erich Minar

16 PACCOCATH FEM trial SFA; binary restenosis rate at 6 month visit, n=87 50% 45% 47% p=0.035 binary restenosis rate [%] 40% 35% 30% 25% 20% 15% 10% 5% 19% 0% control Paccocath Werk, Deutscher Röntgenkongress 2007

17 PACCOCATH - Clinical program PACCOCATH ISR I/II (DE; ISR; vs. POBA; n=108): 2 year fu TCT 07 THUNDER (DE; SFA; n=154): 1 year fu TCT 07 PACCOCATH FEM (DE; SFA; n=87) PEPCAD I (DE; SeQuent Please; small vessels; n=120): 6 mo fu TCT 07 PEPCAD II (DE; ISR; SeQuent Please vs. Taxus; n=130): 6 mo fu TCT 07 PEPCAD III (EU; de novo; DEBlue vs. Cypher; n=600) PEPCAD IV (Asia; diabetics; DEBlue vs. Taxus; n=128) PEPCAD V (DE; bifurcation lesions, SeQuent Please + Coroflex Blue; n=30)

18 PEPCAD trials The Paclitaxel-Eluting PTCA-Balloon Catheter in Coronary Artery Disease B.Braun Vascular Systems, Berlin, Germany SeQuent Please TM is manufactured based on PACCOCATH technology 3 µg paclitaxel / mm² CE mark expected in QII 2008

19 PEPCAD I SVD The Paclitaxel-Eluting PTCA-Balloon Catheter to Treat Small Vessel Coronary Artery Disease. A Pilot Study prospective, non-randomized, multi-center, one-arm phase-ii pilot study De-novo lesions, reference diameter mm; Sequent Please PI: M. Unverdorben, Clinical Research Institute, Rotenburg a.d.f. / Richmond, VA CRO und Core Lab: R. Degenhardt, Clinical Research Institute, Rotenburg a.d.f. Wednesday, October , Main area Late Breaking Studies and First Report Investigations F.X. Kleber, Unfallkrankenhaus Berlin H. Heuer, N. Schulze-Waltrup; St. Johannes Hospital, Dortmund 1:29 pm - PEPCAD I SVD and PEPCAD II: Investigations of a Paclitaxel- Eluting Balloon in Small Vessels and In-Stent Restenosis Lesions: 6-Month Clinical and Angiographic Results Martin Unverdorben H. Figulla; Universitätsklinikum, Jena C. Vallbracht; HKZ, Rotenburg a.d.f. M. Leschke; Städt. Kliniken, Esslingen H. Kücherer; Universitätsklinikum, Heidelberg 1:41 pm - Critical Appraisal of the PEPCAD I SVD and PEPCAD II Studies Antonio Colombo B. Scheller; Universitätsklinikum des Saarlandes, Homburg/Saar M. Buerke; Universitätsklinikum, Halle C. Hamm, M. Rau; Kerckhoff Klinik, Bad Nauheim

20 PEPCAD II ISR The Paclitaxel-Eluting PTCA-Balloon Catheter in Coronary Artery Disease to Treat In-Stent Restenoses: A Comparison to the Paclitaxel-Eluting Taxus Stent - A Pilot Study prospective, randomized, multi-center, two-armed phase-ii pilot study Taxus vs. Sequent Please in coronary ISR PI: M. Unverdorben, Clinical Research Institute, Rotenburg a.d.f. / Richmond, VA CRO und Core Lab: R. Degenhardt, Clinical Research Institute, Rotenburg a.d.f. B. Scheller; Universitätsklinikum des Saarlandes, Homburg/Saar Wednesday, October , Main area Late Breaking Studies and First Report Investigations C. Vallbracht; HKZ, Rotenburg a.d.f. H. Heuer, N. Schulze-Waltrup; St. Johannes Hospital, Dortmund 1:29 pm - PEPCAD I SVD and PEPCAD II: Investigations of a Paclitaxel- Eluting Balloon in Small Vessels and In-Stent Restenosis Lesions: 6-Month Clinical and Angiographic Results Martin Unverdorben C.Hengstenberg, Universitätsklinikum, Regensburg C. Hamm, M. Rau; Kerckhoff Klinik, Bad Nauheim D. Antoni; Krankenhaus Bogenhausen, München W. Bocksch; Charité Virchow, Berlin G. 1:41 Werner; pm - Critical Klinikum, Appraisal Darmstadt of the PEPCAD I SVD and PEPCAD II Studies Antonio Colombo M. Leschke; Städt. Kliniken, Esslingen F.X. Kleber, Unfallkrankenhaus Berlin H. Figulla; Universitätsklinikum, Jena

21 Paclitaxel-Eluting PTCA-Balloon in Combination with the Coroflex Blue Stent vs. the Sirolimus Coated Cypher Stent in the Treatment of Advanced Coronary Artery Disease n = 600 patients, European multicenter trial, complex de-novo lesions Christian Hamm, Bad Nauheim Bruno Scheller, Homburg/Saar IKKF, München; B.Braun Vascular Systems, Berlin W. Aengevaeren, Arnhem, Netherlands P. Barragan, Ollioules, France W. Bocksch, Berlin, Germany J. Bronzwaer, Amsterdam, Netherlands P. Coste, Pessac, France J. Diaz, Huelva, Espagnol E. Eeckhout, Lausanne, Switzerland E. Garcia, Madrid, Espangnol C. Hamm, Bad Nauheim, Germany C. Hehrlein, Freiburg, Germany H. Heuer, Dortmund, Germany B. Huret, Caen, France B. Janek, Praque, Czech Republic G. Olivecrona, Lund, Sweden F. Mauri, Badalona, Spain C. Nienaber, Rostock, Germany B. Scheller, Homburg/Saar, Germany B. Schieffer, Hannover, Germany M. Vrolix, Genk, Belgium N. Wheeldon, Sheffield, United Kingdom W. Wijns, Aalst, Belgium U. Zeymer, Ludwigshafen, Germany

22 Compassionate Use ( Heilversuch ) 70 year old female; repeated restenosis in RCA and LAD after BMS, DES-in-stent and reptca, rejected by surgeons December 2006

23 Compassionate Use Sequent Please 12/06 Sequent Please uncoated balloon 05/07

24 Inhibition of restenosis by drug-coated balloons based on the PACCOCATH technology does not require stent implantation and sustained drug release at the site of injury.

25 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

26 Thanks! Exp. Radiologie, Charité Mitte (Berlin) Ulrich Speck Klinik für Innere Medizin III, Homburg/Saar Michael Böhm Bodo Cremers Yvonne Clever Nicole Hollinger Bianca Werner Institut für Medizintechnologie GmbH (Magdeburg), Dirk Mahnkopf Anakat GmbH (Berlin) InnoRa GmbH (Berlin) B.Braun Vascular Systems (Berlin) Bayer Schering Pharma AG (Berlin) Clinical trials CRO: Parexel (Berlin), Gimbel (Saarlouis), IKKF (München), CRI (Rotenburg) Core Lab: Dietz (Wiesbaden), Degenhardt (Rotenburg), Beregi (Lille, FR) Peripheral: Tepe (Tübingen), Zeller (Bad Krozingen), Ricke (Berlin), Albrecht (Berlin), Hosten (Greifswald) Coronary: Antoni (München), Bocksch (Berlin), Buerke (Halle), Figulla (Jena), Haghi (Mannheim), Hamm (Bad Nauheim), Hehrlein (Freiburg), Hengstenberg (Regensburg), Heuer (Dortmund), Kleber (Berlin), Kücherer (Heidelberg), Leschke (Esslingen), Mathey (Hamburg), Nienaber (Rostock), Rutsch (Berlin), Schieffer (Hannover), Vallbracht (Rotenburg), Werner (Darmstadt), Zeymer (Ludwigshafen) Barragan (Marseille, FR), Bronzvaer (Amsterdam, NL), Coste (Pessac, FR), Diaz (Huelva, ES), Eeckhout (Lausanne, SUI), Garcia (Madrid, ES), Huret (Caen, FR), Janek (Prag, CZ), Olivecrona (Lund, S), Rosli (Kuala Lumpur, MA), Safari (Pulau Pinang, MA), Sim (Kuching, MA), Unverdorben (USA), Vrolix (Gent, BE), Wan (Kuala Lumpur, MA), Wheeldon (Sheffield, UK), Wijns (Aalst, BE)