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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT01076764
First received: February 25, 2010
Last updated: May 16, 2013
Last verified: May 2013
  Purpose

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

Condition Intervention Phase
Acute Coronary Syndrome
Drug: Otamixaban (XRP0673)
Drug: Otamixaban matching placebo
Drug: Unfractionated Heparin
Drug: Unfractionated Heparin matching placebo
Drug: Eptifibatide
Drug: Eptifibatide matching placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Efficacy: Adjudicated double composite of all-cause of death and new myocardial infarction [ Time Frame: from randomization (day 1) to day 7 ] [ Designated as safety issue: No ]
  • Safety: Adjudicated Thrombolysis In Myocardial Infarction (TIMI) significant bleeding (composite of TIMI major and minor) [ Time Frame: from day 1 to day 7 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Adjudicated Triple efficacy composite of all-cause death, new myocardial infarction and any stroke [ Time Frame: from day 1 to day 7 ] [ Designated as safety issue: No ]
  • Rehospitalization or prolongation of hospitalization due to a new episode of myocardial ischemia/myocardial infarction [ Time Frame: from day 1 to day 30 ] [ Designated as safety issue: No ]
  • Adjudicated all-cause death [ Time Frame: from day 1 to day 30 ] [ Designated as safety issue: No ]
  • Adjudicated Procedural thrombotic complications during the index PCI [ Time Frame: during index PCI ] [ Designated as safety issue: No ]

Enrollment: 13220
Study Start Date: April 2010
Study Completion Date: May 2013
Primary Completion Date: May 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Otamixaban - Dose 1

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 dose 1
  • Drug B: UFH matching placebo

From PCI (downstream use) until 18-24 hour post PCI or hospital discharge whichever comes first:

  • Drug C: Eptifibatide matching placebo
Drug: Otamixaban (XRP0673)

Pharmaceutical form: Intravenous (IV) solution

Route of administration: IV bolus followed by continuous IV infusion

Drug: Unfractionated Heparin matching placebo

Pharmaceutical form: Intravenous (IV) solution

Route of administration: IV bolus followed by continuous IV infusion

Drug: Eptifibatide matching placebo

Pharmaceutical form: Intravenous (IV) solution

Route of administration: IV bolus followed by continuous IV infusion

Experimental: Otamixaban - Dose 2

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 dose 2
  • Drug B: UFH matching placebo

From PCI (downstream use) until 18-24 hour post PCI or hospital discharge whichever comes first:

  • Drug C: Eptifibatide matching placebo
Drug: Otamixaban (XRP0673)

Pharmaceutical form: Intravenous (IV) solution

Route of administration: IV bolus followed by continuous IV infusion

Drug: Unfractionated Heparin matching placebo

Pharmaceutical form: Intravenous (IV) solution

Route of administration: IV bolus followed by continuous IV infusion

Drug: Eptifibatide matching placebo

Pharmaceutical form: Intravenous (IV) solution

Route of administration: IV bolus followed by continuous IV infusion

Active Comparator: UFH + Eptifibatide

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 matching placebo
  • Drug B: UFH

From PCI (downstream use) until 18-24 hour post PCI or hospital discharge whichever comes first:

  • Drug C: Eptifibatide
Drug: Otamixaban matching placebo

Pharmaceutical form: Intravenous (IV) solution

Route of administration: IV bolus followed by continuous IV infusion

Drug: Unfractionated Heparin

Pharmaceutical form: Intravenous (IV) solution

Route of administration: IV bolus followed by continuous IV infusion

Drug: Eptifibatide

Pharmaceutical form: Intravenous (IV) solution

Route of administration: IV bolus followed by continuous IV infusion


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion criteria:

Patient with non ST-segment elevation Acute Coronary Syndrome 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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01076764

  Show 607 Study Locations
Sponsors and Collaborators
Sanofi
Investigators
Study Director: Clinical Sciences & Operations Sanofi
  More Information

No publications provided by Sanofi

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT01076764     History of Changes
Other Study ID Numbers: EFC6204, 2009-016568-36
Study First Received: February 25, 2010
Last Updated: May 16, 2013
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Angina, Unstable
Infarction
Myocardial Infarction
Acute Coronary Syndrome
Angina Pectoris
Myocardial Ischemia
Heart Diseases
Cardiovascular Diseases
Vascular Diseases
Chest Pain
Pain
Signs and Symptoms
Ischemia
Pathologic Processes
Necrosis
Calcium heparin
Heparin
Eptifibatide
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents
Platelet Aggregation Inhibitors

ClinicalTrials.gov processed this record on July 28, 2014