Clinical trial NCT00064428: OASIS-6 : The Safety and Efficacy of Fondaparinux Versus Control Therapy in Patients With ST Segment Elevation Acute Myocardial Infarction
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Thromboembolism
Keywords: ST-segment elevation myocardial infarction
fondaparinux
Acute Myocardial Infarction
acute coronary syndrome
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: Sanofi
First posted: 2003-10-17
Enrollment: 12092
Sex: ALL
Minimum age (years): 21
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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

Eligibility criteria: Inclusion Criteria:

* Subjects who presented or were admitted to hospital with:

  1. Signs and symptoms of AMI
  2. Were able to randomize within 12 hours of symptom onset; and-
  3. 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.

Primary outcomes:
measure: Death or recurrent myocardial infarction
timeFrame: up to day 30
measure: Severe hemorrhage
timeFrame: up to Day 9
Secondary outcomes:
measure: Death or recurrent myocardial infarction
timeFrame: up to Day 9, 90 and 180
measure: Death, recurrent myocardial infarction or refractory ischemia
timeFrame: up to Day 9, 30, 90 and 180
Other outcomes:
Locations:
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Yusuf S, Mehta SR, Chrolavicius S, Afzal R, Pogue J, Granger CB, Budaj A, Peters RJ, Bassand JP, Wallentin L, Joyner C, Fox KA; OASIS-6 Trial Group. Effects of fondaparinux on mortality and reinfarction in patients with acute ST-segment elevation myocardial infarction: the OASIS-6 randomized trial. JAMA. 2006 Apr 5;295(13):1519-30. doi: 10.1001/jama.295.13.joc60038. Epub 2006 Mar 14.
citation: Diaz R, Goyal A, Mehta SR, Afzal R, Xavier D, Pais P, Chrolavicius S, Zhu J, Kazmi K, Liu L, Budaj A, Zubaid M, Avezum A, Ruda M, Yusuf S. Glucose-insulin-potassium therapy in patients with ST-segment elevation myocardial infarction. JAMA. 2007 Nov 28;298(20):2399-405. doi: 10.1001/jama.298.20.2399.