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
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- GlaxoSmithKline
- Enrollment
- 20,078
- Primary Endpoint
- death, myocardial infarction or refractory
Study Overview
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]).
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 21 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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
Arms & Interventions
Fondaparinux
Intervention: Fondaparinux (Drug)
Enoxaparin
Intervention: enoxaparin (Drug)
Outcomes
Primary Outcomes
death, myocardial infarction or refractory
Time Frame: up to and including Day 9
first occurrence of any component of death, myocardial infarction or
major bleeding
Time Frame: Up to Day 9
incidence of adjudicated major bleeding
Secondary Outcomes
- Death, myocardial infarction or refractory(up to Day 9, Day 14, Day 30,)
- Severe bleeding complications(up to and including Day 9, Day)
- major bleeding(up to and including Day 14, Day)
- Any bleeding (major or minor)(up to and including Day 9, Day)
- Death, myocardial infarction(up to Days 9, 14, 30, 90 and)