OASIS-6 : The Safety and Efficacy of Fondaparinux Versus Control Therapy in Patients With ST Segment Elevation Acute Myocardial Infarction

Study Overview
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Brief Summary
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This is a randomized, double blindcontrolled, parallel group, multi-center, multinational study of fondaparinux vs. control in patients with STEMI (ST segment myocardial infarction) randomized within 24 hours of the onset of symptoms.

Detailed Description
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This is a randomized, double blind, controlled, parallel group, multi-center, multinational study of fondaparinux vs. control in patients with STEMI randomized within 24 hours of the onset of symptoms. Patients with confirmed STEMI were assigned into one of the following strata, based on local preference: Stratum 1: No indication for UFH; it is generally accepted that patients receiving streptokinase or those not receiving a thrombolytic agent were assigned to this stratum. Stratum 2: Indication for UFH; it is generally accepted that patients receiving a fibrin-specific agent (such as alteplase, reteplase or tenecteplase) or those undergoing primary PCI were assigned to this stratum. Patients who were ineligible for fibrinolysis (e.g. because of late presentation or absolute contra-indication for reperfusion therapy) may fall into either stratum 1 or stratum 2 at investigator's discretion. Following allocation to one of the strata, patients were randomized to fondaparinux or control treatment. Control treatment was dependent on whether the patient was assigned to stratum 1 or stratum 2: Stratum 1: fondaparinux sc* versus fondaparinux-placebo sc for 8 days or until hospital discharge, whichever was earlier. Stratum 2: fondaparinux sc* for 8 days or until hospital discharge, whichever was earlier and UFH-placebo for 24 to 48 hrs (or single bolus injection immediately prior to procedure in case of primary PCI) versus UFH for 24 to 48 hrs (or single bolus injection immediately prior to procedure in case of primary PCI) and fondaparinux-placebo for 8 days or until hospital discharge, whichever was earlier. (*First dose intravenous bolus) Patients were followed up for 6 months

Official Title
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An International Randomized Study Evaluating the Efficacy and Safety of Fondaparinux Versus Control Therapy in a Broad Range of Patients With ST Segment Elevation Acute Myocardial Infarction.

Conditions
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Thromboembolism

Intervention / Treatment
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* Drug: fondaparinux - UFH not indicated
* Other: Control - UFH not indicated
* Drug: Fondaparinux - UFH indicated
* Drug: Control - UFH


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects who presented or were admitted to hospital with: Signs and symptoms of AMI Were able to randomize within 12 hours of symptom onset; and- Had definite ECG changes indicating STEMI: persistent ST-elevation (≥0.2mV in two contiguous precordial leads, or ≥0.1mV in at least two limb leads), or new left bundle branch block, or ECG changes indicating true posterior MI. Written informed consent Able to be randomized within 24 hours of symptom onset Exclusion Criteria: Age <21 years. Was currently receiving an oral anticoagulant agent with an INR >1.8. Had any contraindication to anticoagulation therapy such as high risk of bleeding or active bleeding. Had hemorrhagic stroke within the last 12 months. Had an indication for anticoagulation other than ACS. Pregnant women or women of child-bearing potential who were not using an effective method of contraception. Had a co-morbid condition with a life-expectancy <6 months. Previous enrollment in one of the fondaparinux ACS trials. Participation in another pharmacotherapeutic study within the prior 30 days or was currently receiving an experimental pharmacological agent. Had a known allergy to heparin or fondaparinux. Had severe renal insufficiency (i.e. serum creatinine ≥3mg/dL or ≥265μmol/L). Had >5000IU UFH administered prior to randomization. Had LMWH administered prior to randomization. Subject had pre-randomization revascularization (PCI) for the index event. Subject had pre-randomization rescue PCI.

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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Fondaparinux - UFH not indicated<br>Subjects with no indication for UFH therapy: 2.5mg od, sc, (1st dose IV) x 8 days or discharge | Drug: fondaparinux - UFH not indicated<br>* 2.5mg od, sc (1st dose IV) x 8 days or discharge<br>|
| Placebo Comparator: Control - UFH not indicated<br>Subjects with no indication for UFH therapy: Fondaparinux-placebo od, sc (1st dose IV) x 8 days or discharge | Other: Control - UFH not indicated<br>* Fondaparinux-placebo od, sc (1st dose IV) x 8 days or discharge<br>|
| Experimental: Fondaparinux - UFH indicated<br>Subjects indicated for UFH: 2.5mg od, sc (1st dose IV) x 8 days or discharge + UFH-placebo IV bolus + 24-48 hr infusion | Drug: Fondaparinux - UFH indicated<br>* 2.5mg od, sc (1st dose IV) x 8 days or discharge + UFH-placebo IV bolus x 24-48 hr infusion<br>|
| Active Comparator: Control - unfractionated heparin<br>Subjects indicated for UFH: UFH IV bolus +12 IU/kg/hr infusion x 24-48 hr + fondaparinux-placebo od, sc (1st dose IV) x 8 days or discharge | Drug: Control - UFH<br>* UFH IV bolus +12 IU/kg/hr infusion x 24-48 hr + fondaparinux-placebo od, sc (1st dose IV) x 8 days or discharge<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death or recurrent myocardial infarction | the first occurrence of any component of death (all-cause mortality) or recurrent myocardial infarction | up to day 30 | 
| Severe hemorrhage | Severe hemorrhage (modified TIMI criteria) | up to Day 9 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Death or recurrent myocardial infarction | The first occurrence of any component of the composite of death (all-cause mortality) or recurrent myocardial infarction | up to Day 9, 90 and 180 | 
| Death, recurrent myocardial infarction or refractory ischemia | The first occurrence of any component of the composite of death (all-cause mortality), recurrent myocardial infarction or refractory ischemia | up to Day 9, 30, 90 and 180 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ST-segment elevation myocardial infarction, fondaparinux, Acute Myocardial Infarction, acute coronary syndrome