Clinical trial NCT00152308: Non-Polymer-Based, Rapamycin-Eluting Stents to Prevent Restenosis
Official title: A Prospective, Placebo-Controlled, Double-Blind, Randomized Study Evaluating the Efficacy of Non-Polymer-Based Coating With Two Different Rapamycin-Dosages for the Prevention of Restenosis After Percutaneous Coronary Interventions
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Coronary Disease
Lead sponsor: Translumina GmbH
Sponsor class: INDUSTRY
First posted: 2005-09-09
Enrollment: 333
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The purpose of the study is to evaluate the effectively of coating of coronary stents with two different doses of rapamycin for the prevention of coronary vessel re-blockage

Detailed description: In-stent restenosis remains the major problem limiting the efficacy of coronary stenting. Either sirolimus or paclitaxel drug-eluting stents have been demonstrated to decrease neointima proliferation resulting in a remarkable reduction of restenosis rate. However, despite the outstanding results achieved with this novel approach to restenosis, some caveats still remain. Although sirolimus markedly decreased the restenosis rate among diabetic patients in SIRIUS trial, the benefit of treatment was modest in those diabetics treated with insulin as well as with lesions longer than 15 mm located in vessels smaller than 2.5 mm. Additionally, in a recent study it was reported that the restenosis rate in high-risk lesions such as coronary bifurcations still remains a problem Data from patient populations other than those enrolled in randomized trials suggest even more caution in the evaluation of the impact of DES on restenosis in the "real world", where the operator must deal with in-stent restenosis, bifurcation lesions, chronic total occlusions, small vessels, and long lesions. The identification of some of the traditional risk factors for restenosis as important predictors for in-DES restenosis could be explained as an insufficient inhibition of tissue reaction and neointimal growth by the antiproliferative action of the specific drug or dose used. This leads to the inference that an individualized approach should be adopted by tailoring the choice and the dosing of eluting drug(s) according to the specific lesion or patient characteristics. On the other hand, although drug-eluting stents are currently considered as the most effective way to reduce in-stent restenosis, their widespread use is hampered by the high costs. Therefore, it is important to develop new methods and techniques that would result in a more effective prevention of in-stent restenosis while being available for a larger number of patients. These considerations as well as the proven efficacy of rapamycin in lowering the rate of coronary restenosis, support the rationality of the concept of on-site coating of stents in the catheterization laboratory with individualized doses of rapamycin after the clinical and the angiographic profiles of the patient scheduled to coronary stenting have been determined

Eligibility criteria: Inclusion Criteria:

Age 18-85 years; Symptoms (stable or unstable angina) or signs of myocardial ischemia; Single de novo diagnosed lesion in a native coronary artery (50-99% DS); Lesion length 8 - 25 mm; Vessel diameter 2.25-3.75 mm; Written informed consent

Exclusion Criteria:

Left main target lesion unprotected by a graft; Ostial and bifurcation target lesion; Severely calcified lesions; Thrombus in target lesion; Tortuosity or angulation of target vessel or lesion; Treatment of nontarget lesions in the same or a different coronary vessel during the index procedure; Contraindications to the study medications; Acute myocardial infarction (\< 48 h); Left ventricular ejection fraction \< 25%; Participation in another trial; Pregnancy or lack of protection against pregnancy during the study Coexisting conditions limiting the life expectancy to less 24 months or that could affect the compliance of patients with protocol; Serum creatinin \>2.0mg/dL; Hemorrhagic diathesis; Leukocyte count \<3500/ml\^3 Platelet count \<100.000/ml\^3

Primary outcomes:
measure: Binary angiographic restenosis at follow-up angiogram
Secondary outcomes:
measure: Target vessel failure (all-cause death, myocardial infarction, or revascularization of the target lesion)
Other outcomes:
Locations:
city: Salzburg
country: Austria
facility: St. Johanns Spital
city: Vienna
country: Austria
facility: Donauspital der Stadt Wien
city: Vienna
country: Austria
facility: Allgemeines Krankenhaus Wien
city: Vienna
country: Austria
facility: Wilhelminenspital der Stadt Wien
city: Munich
country: Germany
facility: Deutsches Herzzentrum Muenchen
city: Munich
country: Germany
facility: Kardiologische Praxis und Praxisklinik
city: Munich
country: Germany
facility: First Medizinische Klinik rechts der Isar
city: Jerusalem
country: Israel
facility: Hadassah University Hospital
city: Tel-Aviv
country: Israel
facility: Sourasky Medical Center
city: Zrifin
country: Israel
facility: Assaf Harofeh Medical Center
Study officials:
affiliation: Deutsches Herzzentrum Muenchen
name: Albert Schomig, MD
role: STUDY_CHAIR
affiliation: Deutsches Herzzentrum Muenchen
name: Adnan Kastrati, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Wilhelminenspital der Stadt Wien
name: Kurt Huber, MD
role: STUDY_DIRECTOR
References:
citation: Hausleiter J, Kastrati A, Wessely R, Dibra A, Mehilli J, Schratzenstaller T, Graf I, Renke-Gluszko M, Behnisch B, Dirschinger J, Wintermantel E, Schomig A; investigators of the individualizable durg-eluting Stent System to Abrogate Restenosis Project. Prevention of restenosis by a novel drug-eluting stent system with a dose-adjustable, polymer-free, on-site stent coating. Eur Heart J. 2005 Aug;26(15):1475-81. doi: 10.1093/eurheartj/ehi405. Epub 2005 Jun 23.
citation: Morice MC, Serruys PW, Sousa JE, Fajadet J, Ban Hayashi E, Perin M, Colombo A, Schuler G, Barragan P, Guagliumi G, Molnar F, Falotico R; RAVEL Study Group. Randomized Study with the Sirolimus-Coated Bx Velocity Balloon-Expandable Stent in the Treatment of Patients with de Novo Native Coronary Artery Lesions. A randomized comparison of a sirolimus-eluting stent with a standard stent for coronary revascularization. N Engl J Med. 2002 Jun 6;346(23):1773-80. doi: 10.1056/NEJMoa012843.
citation: Tanabe K, Serruys PW, Grube E, Smits PC, Selbach G, van der Giessen WJ, Staberock M, de Feyter P, Muller R, Regar E, Degertekin M, Ligthart JM, Disco C, Backx B, Russell ME. TAXUS III Trial: in-stent restenosis treated with stent-based delivery of paclitaxel incorporated in a slow-release polymer formulation. Circulation. 2003 Feb 4;107(4):559-64. doi: 10.1161/01.cir.0000048184.96491.8a.