Michelangelo - Oasis 5

Study Overview
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Brief Summary
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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

Detailed Description
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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]).

Official Title
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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

Conditions
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Thromboembolism

Intervention / Treatment
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* Drug: Fondaparinux
* Drug: enoxaparin


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Enoxaparin<br> | Drug: enoxaparin<br>* enoxaparin 1mg/kg s.c. injection twice daily x 2 to 8 days<br>|
| Experimental: Fondaparinux<br> | Drug: Fondaparinux<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| death, myocardial infarction or refractory | first occurrence of any component of death, myocardial infarction or | up to and including Day 9 | 
| major bleeding | incidence of adjudicated major bleeding | Up to Day 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death, myocardial infarction or refractory | Incidence of the individual components of death, myocardial | up to Day 9, Day 14, Day 30, | 
| major bleeding | incidence of adjudicated major bleeding | up to and including Day 14, Day | 
| Any bleeding (major or minor) | Any bleeding (major or minor) as reported by the investigator as | up to and including Day 9, Day | 
| Severe bleeding complications | Severe bleeding complications according to modified thrombolysis in | up to and including Day 9, Day | 
| Death, myocardial infarction | composite of death, myocardial infarction | up to Days 9, 14, 30, 90 and | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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unstable angina, acute coronary syndrome, fondaparinux sodium, non ST segment elevation myocardial infarction, myocardial infarction