Michelangelo - Oasis 5

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