Michelangelo - Oasis 5

Sponsor

GlaxoSmithKline (Industry)

Overall Status

Completed

CT.gov ID

NCT00139815

Collaborator

University of Chicago (Other), Organon (Industry), Sanofi (Industry), Duke University (Other)

20,078

Enrollment

Arms

Duration (Months)

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Thromboembolism	Drug: Fondaparinux Drug: enoxaparin	Phase 3

Detailed Description

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]).

Study Design

Study Type:

Interventional

Actual Enrollment :

20078 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

Double (Participant, 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

Study Start Date :

Apr 1, 2003

Actual Primary Completion Date :

Dec 1, 2005

Actual Study Completion Date :

Dec 1, 2005

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Enoxaparin	Drug: enoxaparin enoxaparin 1mg/kg s.c. injection twice daily x 2 to 8 days
Experimental: Fondaparinux	Drug: Fondaparinux 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

Arm

Intervention/Treatment

Active Comparator: Enoxaparin

Drug: enoxaparin

enoxaparin 1mg/kg s.c. injection twice daily x 2 to 8 days

Experimental: Fondaparinux

Drug: Fondaparinux

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

Outcome Measures

Primary Outcome Measures

death, myocardial infarction or refractory [up to and including Day 9]
first occurrence of any component of death, myocardial infarction or
major bleeding [Up to Day 9]
incidence of adjudicated major bleeding

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

21 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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