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

NCT ID: NCT00393315

Last Updated: 2010-06-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

120 participants

Study Classification

INTERVENTIONAL

Study Start Date

2005-11-30

Study Completion Date

2007-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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In-Stent Restenosis

Keywords

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in stent restenosis paclitaxel coated balloon catheter pepcad drug eluting balloon

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Interventions

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paclitaxel coated balloon catheter

Intervention Type DEVICE

Eligibility Criteria

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Inclusion Criteria

* 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
* 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

Exclusion Criteria

* 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.
* 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
* 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
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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B. Braun Melsungen AG

INDUSTRY

Sponsor Role collaborator

University Hospital, Saarland

OTHER

Sponsor Role lead

Responsible Party

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University Hospital, Saarland

Principal Investigators

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Martin Unverdorben, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Clinical Research Institute, Center for Cardiovascular Diseases, Heinz-Meise-Strasse 100, D-36199 Rotenburg a.d. Fulda, Germany

Locations

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Kerckhoff-Clinic Bad Nauheim

Bad Nauheim, , Germany

Site Status

Unfallkrankenhaus Berlin

Berlin, , Germany

Site Status

Medizinische Klinik, Kardiologie, Charité - Hochschulmedizin Berlin

Berlin, , Germany

Site Status

Klinikum Darmstadt, Medizinische Klinik I

Darmstadt, , Germany

Site Status

Medizinische Klinik, Kardiologie, St.-Johannes -Hospital

Dortmund, , Germany

Site Status

Städtische Kliniken Esslingen, Klinik für Kardiologie, Angiologie und Pneumologie

Esslingen am Neckar, , Germany

Site Status

University of Saarland, Internal Medicine III

Homburg/Saar, , Germany

Site Status

I. Med. Abteilung, Krankenhaus Bogenhausen

München, , Germany

Site Status

University of Regensburg

Regensburg, , Germany

Site Status

Center for Cardiovascular Diseases, Cardiologic Clinic

Rotenburg A.d. Fulda, , Germany

Site Status

Countries

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Germany

References

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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. doi: 10.1148/radiol.2402051248.

Reference Type BACKGROUND
PMID: 16864669 (View on PubMed)

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. doi: 10.1055/s-2006-933695. No abstract available. German.

Reference Type BACKGROUND
PMID: 16538559 (View on PubMed)

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. doi: 10.1016/j.acra.2005.02.017. No abstract available.

Reference Type BACKGROUND
PMID: 16106539 (View on PubMed)

Scheller B, Speck U, Abramjuk C, Bernhardt U, Bohm M, Nickenig G. Paclitaxel balloon coating, a novel method for prevention and therapy of restenosis. Circulation. 2004 Aug 17;110(7):810-4. doi: 10.1161/01.CIR.0000138929.71660.E0. Epub 2004 Aug 9.

Reference Type BACKGROUND
PMID: 15302790 (View on PubMed)

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. doi: 10.1097/01.rli.0000116125.96544.64.

Reference Type BACKGROUND
PMID: 15076010 (View on PubMed)

Scheller B, Speck U, Schmitt A, Bohm 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. doi: 10.1016/s0735-1097(03)01056-8.

Reference Type BACKGROUND
PMID: 14563585 (View on PubMed)

Scheller B, Speck U, Romeike B, Schmitt A, Sovak M, Bohm 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. doi: 10.1016/s0195-668x(03)00317-8.

Reference Type BACKGROUND
PMID: 12909076 (View on PubMed)

Unverdorben M, Vallbracht C, Cremers B, Heuer H, Hengstenberg C, Maikowski C, Werner GS, Antoni D, Kleber FX, Bocksch W, Leschke M, Ackermann H, Boxberger M, Speck U, Degenhardt R, Scheller B. Paclitaxel-coated balloon catheter versus paclitaxel-coated stent for the treatment of coronary in-stent restenosis: the three-year results of the PEPCAD II ISR study. EuroIntervention. 2015 Dec;11(8):926-34. doi: 10.4244/EIJY14M08_12.

Reference Type DERIVED
PMID: 25169589 (View on PubMed)

Unverdorben M, Vallbracht C, Cremers B, Heuer H, Hengstenberg C, Maikowski C, Werner GS, Antoni D, Kleber FX, Bocksch W, Leschke M, Ackermann H, Boxberger M, Speck U, Degenhardt R, Scheller B. Paclitaxel-coated balloon catheter versus paclitaxel-coated stent for the treatment of coronary in-stent restenosis. Circulation. 2009 Jun 16;119(23):2986-94. doi: 10.1161/CIRCULATIONAHA.108.839282. Epub 2009 Jun 1.

Reference Type DERIVED
PMID: 19487593 (View on PubMed)

Other Identifiers

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PEPCAD II/CRI/05/-02/c-c

Identifier Type: -

Identifier Source: secondary_id

BBM-VS-53

Identifier Type: -

Identifier Source: org_study_id