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

Sanofi

Status and phase: Completed; Phase 3

Conditions: Acute Coronary Syndrome

Treatments: Drug: Otamixaban; Drug: Placebo (for Eptifibatide); Drug: Placebo (for UFH); Drug: Placebo (for Otamixaban); Drug: UFH; Drug: Eptifibatide

Study type: Interventional

Funder types: Industry

Identifiers

NCT01076764

EFC6204

2009-016568-36 (EudraCT Number)

Details and patient eligibility

About

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

Full 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.

Enrollment: 13,220 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

Patient with non-ST-segment elevation Acute Coronary Syndrome (NSTE-ACS) with:

1. Ischemic symptoms (chest pain or equivalent) at rest ≥ 10 minutes within 24 hours of randomization,

   AND

2. 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

3. 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

4. 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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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13,220 participants in 3 patient groups

Otamixaban - 0.080 mg/kg bolus + 0.100 mg/kg/h infusion

Experimental group

Description:

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)

Treatment:

Drug: Placebo (for UFH)

Drug: Placebo (for Eptifibatide)

Drug: Otamixaban

Otamixaban - 0.080 mg/kg bolus + 0.140 mg/kg/h infusion

Experimental group

Description:

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)

Treatment:

Drug: Placebo (for UFH)

Drug: Placebo (for Eptifibatide)

Drug: Otamixaban

UFH + Eptifibatide

Active Comparator group

Description:

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)

Treatment:

Drug: Eptifibatide

Drug: UFH

Drug: Placebo (for Otamixaban)