Michelangelo - Oasis 5
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.
- 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:
- Myocardial Infarction
- Refractory Ischemia
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
|Official Title:||An International, Randomized, Double-blind Study Evaluating the Efficacy and Safety of Fondaparinux Versus Enoxaparin in the Acute Treatment of Unstable Angina/Non ST-segment Elevation MI Acute Coronary Syndromes|
- death, myocardial infarction or refractory [ Time Frame: up to and including Day 9 ] [ Designated as safety issue: No ]first occurrence of any component of death, myocardial infarction or
- major bleeding [ Time Frame: Up to Day 9 ] [ Designated as safety issue: Yes ]incidence of adjudicated major bleeding
- Death, myocardial infarction or refractory [ Time Frame: up to Day 9, Day 14, Day 30, ] [ Designated as safety issue: No ]Incidence of the individual components of death, myocardial
- major bleeding [ Time Frame: up to and including Day 14, Day ] [ Designated as safety issue: Yes ]incidence of adjudicated major bleeding
- Any bleeding (major or minor) [ Time Frame: up to and including Day 9, Day ] [ Designated as safety issue: Yes ]Any bleeding (major or minor) as reported by the investigator as
- Severe bleeding complications [ Time Frame: up to and including Day 9, Day ] [ Designated as safety issue: Yes ]Severe bleeding complications according to modified thrombolysis in
- Death, myocardial infarction [ Time Frame: up to Days 9, 14, 30, 90 and ] [ Designated as safety issue: No ]composite of death, myocardial infarction
|Study Start Date:||March 2003|
|Study Completion Date:||December 2005|
|Primary Completion Date:||December 2005 (Final data collection date for primary outcome measure)|
|Active Comparator: Enoxaparin||
enoxaparin 1mg/kg s.c. injection twice daily x 2 to 8 days
fondaparinux 2.5 mg, s.c. injection once daily x 8 days or Hospital Discharge if earlier and placebo-enoxaparin 1mg/kg s.c. injection twice daily x 2-8 days or until clinically stable
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]).