Effect of Otamixaban Versus Unfractionated Heparin + Eptifibatide in Patients With Unstable Angina/Non ST Elevation Myocardial Infarction Undergoing Early Invasive Strategy

Study Overview
=================
Brief Summary
-----------------
Primary Objective: To demonstrate the superior efficacy (composite of all-cause death + Myocardial Infarction (MI)) of Otamixaban to Unfractionated Heparin (UFH) + Eptifibatide Secondary Objectives: To demonstrate the superior efficacy (composite of all-cause death + MI + any stroke) of Otamixaban as compared to UFH + Eptifibatide To document the effect of Otamixaban on rehospitalization or prolongation of hospitalization due to a new episode of myocardial ischemia/myocardial infarction as compared to UFH + eptifibatide To document the effect on mortality (all cause death) of Otamixaban as compared to UFH + eptifibatide To document the safety of Otamixaban as compared to UFH + eptifibatide To document the effect of Otamixaban on thrombotic procedural complications during the index Percutaneous Coronary Intervention (PCI) as compared to UFH + eptifibatide

Detailed Description
-----------------
Up to the interim analysis, patients are randomized to one of the Otamixaban arms or the control arm (UFH + Eptifibatide). Then after interim analysis, patients will be randomized to the continued Otamixaban arm (per Data Monitoring Committee (DMC) decision based on interim analysis results) or the control arm (UFH + Eptifibatide). Except the DMC, all participants will remain blinded to this decision until the end of study. The total duration of the study period per subject will range between 30 days and 180 days. Study end date being the Day 30 visit of the last randomized patient, follow up will be until Day 180 or study end date whichever comes first.

Official Title
-----------------
Randomized, Double-blind, Triple-dummy Trial to Compare the Efficacy of Otamixaban With Unfractionated Heparin + Eptifibatide, in Patients With Unstable Angina/Non ST Segment Elevation Myocardial Infarction Scheduled to Undergo an Early Invasive Strategy

Conditions
-----------------
Acute Coronary Syndrome

Intervention / Treatment
-----------------
* Drug: Otamixaban
* Drug: Placebo (for Otamixaban)
* Drug: UFH
* Drug: Placebo (for UFH)
* Drug: Eptifibatide
* Drug: Placebo (for Eptifibatide)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion criteria: Patient with non-ST-segment elevation Acute Coronary Syndrome (NSTE-ACS) with: Ischemic symptoms (chest pain or equivalent) at rest ≥ 10 minutes within 24 hours of randomization, AND One of the two following criteria: New ST-segment depression ≥ 0.1 mV (≥1 mm), or transient (< 30 minutes) ST-segment elevation ≥ 0.1 mV (≥ 1 mm) in at least 2 contiguous leads on the electrocardiogram, Elevation of cardiac biomarkers within 24 hours of randomization, defined as elevated troponin T, troponin I, or CK-MB level above upper limit of normal, AND Planned to have a coronary angiography (followed, when indicated, by PCI) as early as possible (after at least 2 hours of treatment with study drug) and within 36 hours (at the latest on Day 3, if justified), AND Informed consent obtained in writing. Exclusion criteria: Revascularization procedure already performed for the qualifying event Acute ST-segment elevation MI. Patient having received curative dose of anticoagulant treatment (including UFH, LMWH, or bivalirudin) for more than 24 hours prior to randomization or who have been treated by abciximab. Inability to discontinue current anticoagulation in order to transition to Investigational Products according to the specified transition timing. Patient who can not be treated by aspirin and clopidogrel (or any other oral antiplatelet agent) according to their local labeling. Patient who cannot be treated with eptifibatide according to the national labeling (when available). In countries where eptifibatide is not approved the reference label to be considered is either the European labeling or the US labeling Patient who cannot be treated with unfractionated heparin according to the national labeling. Allergy to otamixaban. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Otamixaban - 0.080 mg/kg bolus + 0.100 mg/kg/h infusion<br>From randomization until the end of the PCI or, if no PCI, up to Day 4 or hospital discharge whichever comes first: Drug A: Otamixaban (0.080 mg/kg bolus followed by 0.100 mg/kg/h infusion) Drug B: Placebo (for UFH) From PCI (downstream use) until 18-24 hour post PCI or hospital discharge whichever comes first: Drug C: Placebo (for Eptifibatide) | Drug: Otamixaban<br>* Pharmaceutical form: Intravenous (IV) solution Route of administration: IV bolus followed by continuous IV infusion<br>* Other names: XRP0673;Drug: Placebo (for UFH)<br>* Pharmaceutical form: Intravenous (IV) solution Route of administration: IV bolus followed by continuous IV infusion<br>Drug: Placebo (for Eptifibatide)<br>* Pharmaceutical form: Intravenous (IV) solution Route of administration: IV bolus followed by continuous IV infusion<br>|
| Experimental: Otamixaban - 0.080 mg/kg bolus + 0.140 mg/kg/h infusion<br>From randomization until the end of the PCI or, if no PCI, up to Day 4 or hospital discharge whichever comes first: Drug A: Otamixaban 0.080 mg/kg bolus followed by 0.140 mg/kg/h infusion) Drug B: Placebo (for UFH) From PCI (downstream use) until 18-24 hour post PCI or hospital discharge whichever comes first: Drug C: Placebo (for Eptifibatide) | Drug: Otamixaban<br>* Pharmaceutical form: Intravenous (IV) solution Route of administration: IV bolus followed by continuous IV infusion<br>* Other names: XRP0673;Drug: Placebo (for UFH)<br>* Pharmaceutical form: Intravenous (IV) solution Route of administration: IV bolus followed by continuous IV infusion<br>Drug: Placebo (for Eptifibatide)<br>* Pharmaceutical form: Intravenous (IV) solution Route of administration: IV bolus followed by continuous IV infusion<br>|
| Active Comparator: UFH + Eptifibatide<br>From randomization until the end of the PCI or, if no PCI, up to Day 4 or hospital discharge whichever comes first: Drug A: Placebo (for Otamixaban) Drug B: UFH (60 IU/kg bolus followed by 12 IU/kg/h infusion) From PCI (downstream use) until 18-24 hour post PCI or hospital discharge whichever comes first: Drug C: Eptifibatide (180 mcg/kg bolus followed by 2 mcg/kg/min infusion) | Drug: Placebo (for Otamixaban)<br>* Pharmaceutical form: Intravenous (IV) solution Route of administration: IV bolus followed by continuous IV infusion<br>Drug: UFH<br>* Pharmaceutical form: Intravenous (IV) solution Route of administration: IV bolus followed by continuous IV infusion<br>* Other names: Unfractionated Heparin;Drug: Eptifibatide<br>* Pharmaceutical form: Intravenous (IV) solution Route of administration: IV bolus followed by continuous IV infusion<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Efficacy: Adjudicated double composite of all-cause of death and new myocardial infarction |  | from randomization (day 1) to day 7 | 
| Safety: Adjudicated Thrombolysis In Myocardial Infarction (TIMI) significant bleeding (composite of TIMI major and minor) |  | from day 1 to day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Adjudicated Triple efficacy composite of all-cause death, new myocardial infarction and any stroke |  | from day 1 to day 7 | 
| Rehospitalization or prolongation of hospitalization due to a new episode of myocardial ischemia/myocardial infarction |  | from day 1 to day 30 | 
| Adjudicated all-cause death |  | from day 1 to day 30 | 
| Adjudicated Procedural thrombotic complications during the index PCI |  | during index PCI |