Clinical trial NCT00139815: Michelangelo - Oasis 5
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Thromboembolism
Keywords: unstable angina
acute coronary syndrome
fondaparinux sodium
non ST segment elevation myocardial infarction
myocardial infarction
Lead sponsor: GlaxoSmithKline
Sponsor class: INDUSTRY
Collaborators: name: University of Chicago
name: Organon
name: Sanofi
name: Duke University
First posted: 2005-08-31
Enrollment: 20078
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: 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: 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 \[CABG\]).

Eligibility criteria: 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

Primary outcomes:
measure: death, myocardial infarction or refractory
timeFrame: up to and including Day 9
measure: major bleeding
timeFrame: Up to Day 9
Secondary outcomes:
measure: Death, myocardial infarction or refractory
timeFrame: up to Day 9, Day 14, Day 30,
measure: major bleeding
timeFrame: up to and including Day 14, Day
measure: Any bleeding (major or minor)
timeFrame: up to and including Day 9, Day
measure: Severe bleeding complications
timeFrame: up to and including Day 9, Day
measure: Death, myocardial infarction
timeFrame: up to Days 9, 14, 30, 90 and
Other outcomes:
Locations:
Study officials:
affiliation: GlaxoSmithKline
name: GSK Clinical Trials
role: STUDY_DIRECTOR
References:
citation: Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators; Yusuf S, Mehta SR, Chrolavicius S, Afzal R, Pogue J, Granger CB, Budaj A, Peters RJ, Bassand JP, Wallentin L, Joyner C, Fox KA. Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med. 2006 Apr 6;354(14):1464-76. doi: 10.1056/NEJMoa055443. Epub 2006 Mar 14.
citation: Chow CK, Jolly S, Rao-Melacini P, Fox KA, Anand SS, Yusuf S. Association of diet, exercise, and smoking modification with risk of early cardiovascular events after acute coronary syndromes. Circulation. 2010 Feb 16;121(6):750-8. doi: 10.1161/CIRCULATIONAHA.109.891523. Epub 2010 Feb 1.
citation: Bassand JP, Afzal R, Eikelboom J, Wallentin L, Peters R, Budaj A, Fox KA, Joyner CD, Chrolavicius S, Granger CB, Mehta S, Yusuf S; OASIS 5 and OASIS 6 Investigators. Relationship between baseline haemoglobin and major bleeding complications in acute coronary syndromes. Eur Heart J. 2010 Jan;31(1):50-8. doi: 10.1093/eurheartj/ehp401. Epub 2009 Oct 12.