michelangelo - oasis 5

Conditions: Thromboembolism

Summary: study objectives primary objective: to evaluate whether fondaparinux is at least as effective as or superior to enoxaparin in preventing death, myocardial infarction or refactory ischemia up to day 9 in the acute treatment of patients with unstable angina/non st-segment elevation myocardial infarction concurrently managed with standard medical therapy. secondary objective: if non inferiority of fondaparinux is established on initial statistical analysis in a second step, superiority of fondaparinux to enoxaparin will be evaluated statistically. * to determine whether fondaparinux is superior to enoxaparin in reducing death or mi at day 9 * to determine whether fondaparinux is superior to enoxaparin in reducing major bleeding events up to day 9 * to determine whether the relative effect on the primary end point of fondaparinux versus enoxaparin is sustained at day 14, day 30, day 90 and day 180 study drug: patients will be randomized to receive either: * fondaparinux 2.5 mg once and placebo-enoxaparin twice daily by subcutaneous injection or * enoxaparin (1mg/kg) twice and fondaparinux-placebo once daily by subcutaneous injection duration of therapy: * fondaparinux 2.5mg daily for 8 days or hospital discharge (whichever is earlier) * enoxaparin 1mg/kg b.i.d. x 2-8 days or until clinically stable. * patients should receive an asa and all other standard medical therapies. substudy: * a substudy comparing routine early coronary angiography immediately or as soon as possible (but no later than 24 hours after randomization) and intervention versus delayed (\>48 hrs) coronary angiography and intervention. primary outcome: the first occurence of any component of the following composite up to day 9: * death * myocardial infarction * refractory ischemia

this is a double-blind, double-dummy, randomized, parallel-group, controlled trial to compare the safety and efficacy of fondaparinux and enoxaparin in subjects with ua/nstemi (unstable angina/non st segment myocardial infarction). study drug (s.c.) was started immediately following randomization; subjects received fondaparinux 2.5mg once daily s.c for 8 days or until hospital discharge, if earlier, or enoxaparin 1mg/kg twice daily s.c for 2 to 8 days or until clinically stable. in subjects with creatinine clearance between 20ml/min and 30ml/min, enoxaparin was administered as 1mg/kg once daily. in addition to study drug, subjects were to receive standard medical care, including interventions (pci \[percutaneous coronary intervention\] or coronary artery bypass graft surgery \[cabg\]).

Eligibility criteria:
inclusion criteria: * patients presenting or admitted to hospital with symptoms suspected to represent an acute coronary syndrome. * able to randomize within 24 hours of the onset of the most recent episode of symptoms. * at least one of the following additional criteria: (1) troponin t of i or ck-mb above the upper limit of normal for the local institution and/or (2) ecg changes compatible with ischemia * written informed consent exclusion criteria: * age \< 21 years * any contraindication to low molecular weight heparin * hemorrhagic stroke within the last 12 months * indication for anticoagulation other than acs. * pregnancy or women of childbearing potential who are not using an effective method of contraception * co-morbid condition with life expectancy less than 6 months * prior enrollment in one of the fondaparinux acs trails or currently receiving an experimental pharmacologic agent

Keywords: unstable angina acute coronary syndrome fondaparinux sodium non st segment elevation myocardial infarction myocardial infarction