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

University Hospital, Saarland

Status and phase

Completed

Phase 2

Conditions

In-Stent Restenosis

Treatments

Device: paclitaxel coated balloon catheter

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00393315

BBM-VS-53

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

Details and patient eligibility

About

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.

Full 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.

Enrollment

120 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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