Michelangelo - Oasis 5

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 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

Study Overview

• Status: Completed
• Conditions: Thromboembolism
• Intervention / Treatment: Drug: enoxaparin; Drug: Fondaparinux

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 Type: Interventional
• Enrollment (Actual): 20078
• Phase: Phase 3

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
death, myocardial infarction or refractory	first occurrence of any component of death, myocardial infarction or	up to and including Day 9
major bleeding	incidence of adjudicated major bleeding	Up to Day 9

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: GlaxoSmithKline
• Collaborators: Sanofi; University of Chicago; Duke University; Organon

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Helpful Links

• Researchers can use this site to request access to anonymised patient level data and/or supporting documents from clinical studies to conduct further research.

Study record dates

Study Major Dates

• Study Start: April 1, 2003
• Primary Completion (Actual): December 1, 2005
• Study Completion (Actual): December 1, 2005

Study Registration Dates

• First Submitted: August 29, 2005
• First Submitted That Met QC Criteria: August 29, 2005
• First Posted (Estimate): August 31, 2005

Study Record Updates

• Last Update Posted (Estimate): September 15, 2016
• Last Update Submitted That Met QC Criteria: September 13, 2016
• Last Verified: September 1, 2016

More Information

Terms related to this study

• Keywords: acute coronary syndrome; myocardial infarction; unstable angina; fondaparinux sodium; non ST segment elevation myocardial infarction
• Additional Relevant MeSH Terms: Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thromboembolism; Acute Coronary Syndrome; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Fibrinolytic Agents; Fibrin Modulating Agents; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Enoxaparin; Fondaparinux; PENTA
• Other Study ID Numbers: 103420

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Patient-level data for this study will be made available through www.clinicalstudydatarequest.com following the timelines and process described on this site.

Study Data/Documents

1. Clinical Study Report
   Information identifier: 103420
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
2. Individual Participant Data Set
   Information identifier: 103420
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
3. Annotated Case Report Form
   Information identifier: 103420
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
4. Statistical Analysis Plan
   Information identifier: 103420
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
5. Dataset Specification
   Information identifier: 103420
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
6. Study Protocol
   Information identifier: 103420
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register
7. Informed Consent Form
   Information identifier: 103420
   Information comments: For additional information about this study please refer to the GSK Clinical Study Register