Clinical trial NCT00859183: Oral Sirolimus for In-Stent Restenosis
Official title: A Randomized, Double-Blind, Placebo-Controlled Trial Investigating the Impact of Oral Sirolimus on Restenosis Prevention in Patients With In-Stent Restenosis.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE4
Conditions: Coronary Restenosis
Keywords: in-stent restenosis
stents
sirolimus
Lead sponsor: Deutsches Herzzentrum Muenchen
Sponsor class: OTHER
First posted: 2009-03-10
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: Despite recent advances in interventional cardiology including the success of drug-eluting stents in de-novo coronary lesions, the treatment of in-stent restenosis remains a challenging clinical issue. Given the efficacy of the systemic sirolimus administration to prevent neointimal hyperplasia in animal models and to halt and even reverse the progression of allograft vasculopathy, the aim of the present double-blind, placebo-controlled study was to evaluate the efficacy of a 10-day oral sirolimus treatment with two different loading regimens for the prevention of recurrent restenosis in patients with in-stent restenosis.

Detailed description: Three-hundred symptomatic patients with in-stent restenotic lesions were randomly assigned to one of three treatment arms: placebo, usual dose or high dose sirolimus. Patients received a cumulative loading dose of 0, 8 or 24 mg of sirolimus two days prior to and the day of repeat intervention followed by maintenance therapy of 2 mg/day for 7 days. Angiographic restenosis at 6-months angiography was the primary end point of the study.

Eligibility criteria: Inclusion Criteria:

* Patients with angina pectoris or exercise-induced ischemia in the presence of angiographically significant in-stent-restenosis in native coronary arteries.

Exclusion Criteria:

* Patients with acute coronary syndromes or with severe infectious diseases the presence of severe kidney failure (serum creatinine \> 2.2 mg/dl) contraindications to sirolimus

Primary outcomes:
measure: Angiographic restenosis
timeFrame: 6 months
Secondary outcomes:
measure: The combined incidence of death and myocardial infarction as well as target vessel revascularization
timeFrame: one year
Other outcomes:
Locations:
city: Garmisch-Partenkirchen
country: Germany
facility: Medizinische Klinik I, Garmisch-Partenkirchen
city: Munich
country: Germany
facility: Deutsches Herzzentrum
city: Munich
country: Germany
facility: 1. Medizinische Klinik, Klinikum rechts der Isar
Study officials:
affiliation: Deutsches Herzzentrum Muenchen
name: Adnan Kastrati, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Deutsches Herzzentrum Muenchen
name: Albert Schömig, MD
role: STUDY_CHAIR
References:
citation: Hausleiter J, Kastrati A, Mehilli J, Vogeser M, Zohlnhofer D, Schuhlen H, Goos C, Pache J, Dotzer F, Pogatsa-Murray G, Dirschinger J, Heemann U, Schomig A; OSIRIS Investigators. Randomized, double-blind, placebo-controlled trial of oral sirolimus for restenosis prevention in patients with in-stent restenosis: the Oral Sirolimus to Inhibit Recurrent In-stent Stenosis (OSIRIS) trial. Circulation. 2004 Aug 17;110(7):790-5. doi: 10.1161/01.CIR.0000138935.17503.35. Epub 2004 Aug 9.
citation: Kufner S, Hausleiter J, Ndrepepa G, Schulz S, Bruskina O, Byrne RA, Fusaro M, Kastrati A, Schomig A, Mehilli J; OSIRIS Trial Investigators. Long-term risk of adverse outcomes and new malignancies in patients treated with oral sirolimus for prevention of restenosis. JACC Cardiovasc Interv. 2009 Nov;2(11):1142-8. doi: 10.1016/j.jcin.2009.08.015.