P E P C A D II, The Paclitaxel-Eluting PTCA-Balloon Catheter in Coronary Artery Disease to Treat In-Stent Restenoses

In-Stent Restenosis Clinical Trial

Official title:

P E P C A D II, 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00393315
• Other study ID #: BBM-VS-53
• Secondary ID: PEPCAD II/CRI/05
• Status: Completed
• Phase: Phase 2
• First received: October 26, 2006
• Last updated: June 29, 2010
• Start date: November 2005
• Est. completion date: December 2007

Study information

• Verified date: June 2010
• Source: University Hospital, Saarland
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial Summary

The aim of the study is to assess the safety and efficacy of the Paclitaxel-eluting PTCA-balloon in the treatment of in-stent restenoses in native coronary arteries with reference diameters between 2.5 mm and 3.5 mm and ≤ 22 mm in length for procedural success and preservation of vessel patency in comparison to the Paclitaxel-eluting Taxus™ stent.

Description:

Background information:

Stent deployment for the treatment of coronary artery stenoses has evolved as the standard treatment in nearly all types of coronary lesions over the past two decades.The initial recurrence rate of bare stents in the range of 20 30 % in low risk stenoses has been further reduced by devices with passive coatings such as silicon carbide, heparin, phosphorylcholine, and carbon. The significant decline of in-stent restenoses (= ISR) to the order of 12 % was achieved by active coatings like the cell-cycle inhibitor sirolimus and to about 13.7 % by the cytotoxic paclitaxel. Taken into account the more than one million annual stent procedures performed worldwide even low recurrence rates will leave some hundred thousand repeat procedures annually. In the treatment of in-stent restenoses, however, approaches such as stand alone angioplasty with conventional balloons, the repeat use of bare stents, cutting balloon angioplasty, rotablation, and atherectomy have revealed unsatisfactory and often conflicting results. For brachytherapy the late loss was reported in the range from 0.22 +/- 0.84 mm to 0.73 +/- 0.79mm. Due to its disadvantages such as delayed endothelialization with ensuing late thrombosis cumulating in a 12-months cardiac event rate of up to 30% rising to 50% after five years, its decrease of benefit over time, and the cumbersome logistics at the sites and in the labs, brachytherapy is not considered as a valid approach of the future. Recently, the deployment of drug eluting stents into a restenotic device was associated with restenosis rates in the range from 4% to 30% suggesting some advantage over the aforementioned approaches. The wide range of the results and some late cardiac events still leave room for alternative methods such as the Paclitaxel-eluting PTCA balloon catheter.

Study Rationale The principle of the Paclitaxel-eluting PTCA balloon catheter is based on the antiproliferative mode of action of the compound, the latter being homogenously distributed along the entire length of the balloon and, hence, the vessel segment to be treated. This advantage is in particular relevant in comparison to drug eluting stents as are the lack of chronic mechanical alterations of the artery, the ease of access to the lesion, the obviation of adding another layer of metal to the lesion, and the presumably lower cost of the procedure. Data on the use of the Paclitaxel-eluting PTCA balloon catheter on the treatment of in-stent restenoses, however, are scant. In the animal model and according to unpublished results in humans, the proliferation induced by a Paclitaxel-eluting balloon catheter was significantly less compared to an uncoated balloon and to the Sirolimus-eluting Cypher™ stent.Therefore, it is prudent to compare the direct arterial application of Paclitaxel by means of the Paclitaxel-eluting PTCA balloon catheter versus the Paclitaxel-eluting Taxus™-stent as percutaneous transluminal treatment options of in-stent restenosis in human coronary arteries in a prospective randomized pilot study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: December 2007
• Est. primary completion date: December 2006
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria: Patient Related

• Patients with stable angina pectoris (CCS class 1-3) or with unstable angina pectoris (Braunwald class 1-2, A-C) or documented ischemia or with documented silent ischemia

• Patients eligible for coronary revascularization by means of PCI

• Age at least 18 years of age

• Women of childbearing potential may not be pregnant nor have the desire to becoming pregnant during the first year following the study procedure. Hence, patients will be advised to use an adequate birth control method up to and including 6 months follow-up

• Patients must agree to undergo the 6 months angiographic follow-up and the 1 and 3 year clinical follow-up Inclusion Criteria: Lesion Related

• In-stent restenosis or Mehran type III stenoses reaching = 2 mm into the adjacent native vessel of a metal stent (including passive coatings, exclusive of active coatings), i.e., no recurrence in the native vessel adjacent to the stent, after stent deployment in a native coronary artery (reference vessel between 2.5 and 3.5 mm, lesion length = 22 mm as angiographically documented)

• Diameter stenosis pre procedure must be either at least 70 % or 50 % if ischemia corresponding to the target lesion is documented either by exercise stress ECG, stress echocardiography, scintigraphy, MRT, or suspected based on angina pectoris

• In the stent group, the target lesion must be treated with a single stent only (multiple stenting shifts the patient to the intention-to-treat group) Exclusion Criteria: Patient Related

• Patients with acute (< 24 h) or recent (48 hours) myocardial infarction, unstable angina pectoris (Braunwald class 3)

• Clinical signs of cardiogenic shock at the time of the procedure (systolic blood pressure of less than 80 mmHg requiring inotropic support, IABP and/or fluid challenge)

• Patients with another coronary stent implanted previously into the target vessel

• Patients with bleeding diathesis in whom anticoagulation or anti-platelet medication is contraindicated

• Patients who had a cerebral stroke < 6 months prior to the procedure

• Patient participates in other clinical trials involving any investigational device or drug

• Untreated hyperthyroidism

• Patient has presence or history of severe renal failure (GFR<30ml/min) and is therefore not eligible for angiography. Patient's serum creatinine levels must be documented

• Post transplantation of any organ or immune suppressive medication

• Other disease to jeopardize follow-up (e.g., malignoma)

• Patients with any type of surgery during the week preceding the interventional procedure.

• Therapy with anticogulants Exclusion Criteria: Lesion Related

• Evidence of extensive thrombosis within target vessel before the intervention

• Side branch > 2 mm in diameter originating from the stent

• Bifurcate lesion

• Left main coronary artery stenosis

• Multilesion percutaneous coronary intervention within the same artery

• Percutaneous coronary intervention of venous graft

• Coronary artery occlusions of any type

• In-stent restenosis of a drug eluting stent (DES)

• In-segment stenosis of the native vessel within the 5 mm adjacent to the stent

• Lesion within 1 mm of vessel origin

• Exclusion Criteria Related to Concomitant Medication

• Patient is intolerant to aspirin and/or the ADP-antagonists clopidogrel or has a history of neutropenia, thrombocytopenia induced by ADP-antagonists, or severe hepatic dysfunction prohibiting the use of clopidogrel

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Coronary Artery Disease
• Coronary Disease
• In-Stent Restenosis
• Myocardial Ischemia

Intervention

Device:
• paclitaxel coated balloon catheter

Locations

Country	Name	City	State
Germany	Kerckhoff-Clinic Bad Nauheim	Bad Nauheim
Germany	Medizinische Klinik, Kardiologie, Charité - Hochschulmedizin Berlin	Berlin
Germany	Unfallkrankenhaus Berlin	Berlin
Germany	Klinikum Darmstadt, Medizinische Klinik I	Darmstadt
Germany	Medizinische Klinik, Kardiologie, St.-Johannes -Hospital	Dortmund
Germany	Städtische Kliniken Esslingen, Klinik für Kardiologie, Angiologie und Pneumologie	Esslingen
Germany	University of Saarland, Internal Medicine III	Homburg/Saar
Germany	I. Med. Abteilung, Krankenhaus Bogenhausen	München
Germany	University of Regensburg	Regensburg
Germany	Center for Cardiovascular Diseases, Cardiologic Clinic	Rotenburg a.d. Fulda

Sponsors (2)

Lead Sponsor	Collaborator
University Hospital, Saarland	B. Braun Melsungen AG

Country where clinical trial is conducted

Germany, 

References & Publications (7)

Custodis F, Scheller B, Laufs U. [Stable coronary artery disease -- case report]. Dtsch Med Wochenschr. 2006 Mar 17;131(11):554-5; quiz 563-4. German. — View Citation

Scheller B, Speck U, Abramjuk C, Bernhardt U, Böhm M, Nickenig G. Paclitaxel balloon coating, a novel method for prevention and therapy of restenosis. Circulation. 2004 Aug 17;110(7):810-4. Epub 2004 Aug 9. — View Citation

Scheller B, Speck U, Romeike B, Schmitt A, Sovak M, Böhm M, Stoll HP. Contrast media as carriers for local drug delivery. Successful inhibition of neointimal proliferation in the porcine coronary stent model. Eur Heart J. 2003 Aug;24(15):1462-7. — View Citation

Scheller B, Speck U, Schmitt A, Böhm M, Nickenig G. Addition of paclitaxel to contrast media prevents restenosis after coronary stent implantation. J Am Coll Cardiol. 2003 Oct 15;42(8):1415-20. — View Citation

Speck U, Scheller B, Abramjuk C, Bernhardt U. Drug delivery by angiographic contrast media: inhibition of restenosis. Acad Radiol. 2005 May;12 Suppl 1:S14-7. — View Citation

Speck U, Scheller B, Abramjuk C, Breitwieser C, Dobberstein J, Boehm M, Hamm B. Neointima inhibition: comparison of effectiveness of non-stent-based local drug delivery and a drug-eluting stent in porcine coronary arteries. Radiology. 2006 Aug;240(2):411-8. — View Citation

Speck U, Scheller B, Abramjuk C, Grossmann S, Mahnkopf D, Simon O. Inhibition of restenosis in stented porcine coronary arteries: uptake of Paclitaxel from angiographic contrast media. Invest Radiol. 2004 Mar;39(3):182-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Late lumen loss at 6 months
Secondary	Procedural success
Secondary	Occurrence of acute (up to 48 hours), subacute (up to 30 days), and late thrombosis
Secondary	30-day MACE rate
Secondary	Percent in-stent stenosis at 6 months
Secondary	Percent in-segment stenosis at 6 months
Secondary	In-stent late loss index at 6 months
Secondary	Angiographic binary in-stent stenosis rate at 6 months
Secondary	In-segment late loss index at 6 months
Secondary	Angiographic binary in-segment stenosis rate at 6 months
Secondary	Acute and cumulative MACE rate at 6 months
Secondary	Cumulative MACE rate after one year
Secondary	Cumulative MACE rate after three years
Secondary	Indication for premature follow-up
Secondary	Type of recurrence (Mehran-Classification)
Secondary	Target vessel failure