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

• Register: EUCTR
• Last refreshed on: 3 June 2013
• Main ID: EUCTR2009-016568-36-BG
• Date of registration: 24/09/2010
• Prospective Registration: Yes
• Primary sponsor: sanofi-aventis recherche & développement
• Public title: Effect of Otamixaban Versus Unfractionated Heparin + Eptifibatide in Patients With Unstable Angina/Non ST Elevation Myocardial Infarction Undergoing Early Invasive Strategy (TAO)
• Scientific 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 - TAO
• Date of first enrolment: 23/12/2010
• Target sample size: 13220
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2009-016568-36
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: yes Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: yes Placebo: no Other: no Number of treatment arms in the trial: 3

Countries of recruitment

Argentina, Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, Chile, Colombia, Croatia, Czech Republic, Egypt, Estonia, France, Germany, Greece, Hong Kong, Hungary, India, Indonesia, Israel, Italy, Jordan, Korea, Republic of, Latvia, Lebanon, Lithuania, Macedonia, the former Yugoslav Republic of, Malaysia, Mexico, Montenegro, Netherlands, New Zealand, Panama, Peru, Portugal, Russian Federation, Serbia, Singapore, South Africa, Spain, Switzerland, Thailand, Tunisia, Turkey, Ukraine, United Kingdom, Vietnam

Contacts

• Affiliation: sanofi-aventis recherche & développement

• Affiliation: sanofi-aventis recherche & développement

Key inclusion & exclusion criteria

Inclusion criteria:
Patient with non ST-segment elevation Acute Coronary Syndrome with the following symptoms:

I 01. Ischemic symptoms (chest pain or equivalent) at rest =10 minutes within 24 hours of randomization

AND
I 02.One of the two following criteria:
I 02A. 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 ECG, OR
I 02B. 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
I 03. 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
I 04. Informed consent obtained in writing

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 7860
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 5360

Exclusion criteria:
Cardiovascular
E 06. Revascularization procedure already performed for the qualifying event.
E 07. Acute ST-segment elevation MI

Related to prior or concomitant treatments
E 08. 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.
E 09. Inability to discontinue current anticoagulation in order to transition to Investigational Products according to the specified transition timing

Exclusion criteria related to the active comparator and/or mandatory background therapies

E 10. Patients who can not be treated by aspirin and clopidogrel (or any other oral antiplatelet agent) according to their local labeling

Related to eptifibatide
E 11. 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 will be either the European labeling or the US labeling.

Related to unfractionated heparin
E 12. Patient who cannot be treated with unfractionated heparin according to the national labeling

Exclusion criteria related to the current knowledge of a sanofi-aventis compound
E 13. Allergy to otamixaban



Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

Acute coronary syndrome scheduled to undergo an early invasive strategy.
MedDRA version: 14.1 Level: PT Classification code 10051592 Term: Acute coronary syndrome System Organ Class: 10007541 - Cardiac disorders

Intervention(s)

Product Name: Otamixaban
Product Code: XRP0673
Pharmaceutical Form: Solution for injection
INN or Proposed INN: otamixaban
CAS Number: 219672-50-1
Current Sponsor code: XRP0673
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous bolus use (Noncurrent)

Product Name: Otamixaban
Product Code: XRP0673
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: otamixaban
CAS Number: 219672-50-1
Current Sponsor code: XRP0673
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 5-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous drip use (Noncurrent)

Trade Name: INTEGRILIN 2 mg/ml
Product Name: INTEGRILIN
Pharmaceutical Form: Solution for injection
INN or Proposed INN: EPTIFIBATIDE
CAS Number: 188627-80-7
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 2-
Pharmaceutical form of the placebo: Solution for injection
Route of administration of the placebo: Intravenous bolus use (Noncurrent)

Trade Name: INTEGRILIN 0.75 mg/ml
Product Name: INTEGRILIN
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: EPTIFIBATIDE
CAS Number: 188627-80-7
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 0.75-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous drip use (Noncurrent)

Trade Name: HEPARINE CHOAY 25 000 UI/5 ml
Product Name: HEPARIN SODIUM
Pharmaceutical Form: Concentrate for solution for injection
INN or Proposed INN: HEPARIN
CAS Number: 9041-08-1
Other descriptive name: HEPARIN SODIUM
Concentration unit: IU/ml international unit(s)/millilitre
Concentration type: equal
Concentration number: 5000-
Pharmaceutical form of the placebo: Solution for in

Primary Outcome(s)

Main Objective: To demonstrate the superior efficacy (composite of all-cause death + Myocardial infarction) of otamixaban as compared to unfractionated heparin (UFH) + eptifibatide.

Timepoint(s) of evaluation of this end point: - Efficacy: Adjudicated double composite of all-cause of death and new
myocardial infarction [Time Frame: from randomization (day 1) to day 7]
- Safety: Adjudicated Thrombolysis In Myocardial Infarction (TIMI)
significant bleeding (composite of TIMI major and minor) [ Time Frame:
from day 1 to
day 7 ]

Secondary Objective: • To demonstrate the superior efficacy ( composite of all-cause death + Myocardial infarction+ 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 mortality) 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 PCI as compared to UFH + eptifibatide
• To characterize otamixaban pharmacokinetics over the entire dosing interval and to evaluate otamixaban exposure-response (safety and efficacy) in the target population

Primary end point(s): Primary efficacy endpoint: Adjudicated composite of all-cause death and new myocardial infarction (MI) from randomization (Day 1) to Day 7. This endpoint will be analyzed from randomization (Day 1) to Day 30 as a sensitivity analysis.
Primary safety endpoint:TIMI significant bleeding (composite of TIMI major and minor) from randomization (Day 1) to Day 7

Secondary Outcome(s)

Secondary end point(s): - Adjudicated Triple efficacy composite of all-cause death, new
myocardial infarction and any stroke
- Rehospitalization or prolongation of hospitalization due to a new
episode of myocardial ischemia/myocardial infarction
- Adjudicated all-cause death
- Adjudicated Procedural thrombotic complications during the index PCI

Timepoint(s) of evaluation of this end point: - Adjudicated Triple efficacy composite of all-cause death, new
myocardial infarction and any stroke [Time Frame: from day 1 to day 7]
- Rehospitalization or prolongation of hospitalization due to a new
episode of myocardial ischemia/myocardial infarction [ Time Frame:
from day 1 to day 30 ]
- Adjudicated all-cause death [ Time Frame: from day 1 to day 30 ]
- Adjudicated Procedural thrombotic complications during the index PCI
[ Time Frame: during index PCI ]

Secondary ID(s)

2009-016568-36-HU

EFC6204

Source(s) of Monetary Support

sanofi-aventis recherche & développement