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

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT00064428

Collaborator

Sanofi (Industry)

12,092

Enrollment

Arms

30.1

Duration (Months)

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Thromboembolism	Drug: fondaparinux - UFH not indicated Other: Control - UFH not indicated Drug: Fondaparinux - UFH indicated Drug: Control - UFH	Phase 3

Detailed Description

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

Study Design

Study Type:

Interventional

Actual Enrollment :

12092 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Primary Purpose:

Treatment

Official Title:

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.

Study Start Date :

Aug 1, 2003

Actual Primary Completion Date :

Feb 1, 2006

Actual Study Completion Date :

Feb 1, 2006

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

Death or recurrent myocardial infarction [up to day 30]
the first occurrence of any component of death (all-cause mortality) or recurrent myocardial infarction
Severe hemorrhage [up to Day 9]
Severe hemorrhage (modified TIMI criteria)

Secondary Outcome Measures

Death or recurrent myocardial infarction [up to Day 9, 90 and 180]
The first occurrence of any component of the composite of death (all-cause mortality) or recurrent myocardial infarction
Death, recurrent myocardial infarction or refractory ischemia [up to Day 9, 30, 90 and 180]
The first occurrence of any component of the composite of death (all-cause mortality), recurrent myocardial infarction or refractory ischemia

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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.