title: Design and rationale of the treatment of acute coronary syndromes with otamixaban trial: a double-blind triple-dummy 2-stage randomized trial comparing otamixaban to unfractionated heparin and eptifibatide in non-ST-segment elevation acute coronary syndromes with a planned early invasive strategy.
abstract: BACKGROUND
  Otamixaban is a synthetic intravenous direct factor Xa inhibitor, with rapid onset/offset, linear kinetics, and no significant renal elimination. A phase II trial in acute coronary syndromes (ACS) showed a marked reduction in the combined end point of death or myocardial infarction (MI) and similar bleeding rates with otamixaban at midrange doses, compared with unfractionated heparin (UFH) and eptifibatide.
  
  
  METHODS
  The TAO trial is a phase III, randomized, double-blind, triple-dummy controlled trial testing the efficacy of otamixaban over UFH plus eptifibatide in patients with non-ST-segment elevation ACS to be treated with dual oral antiplatelet therapy and an invasive strategy. Approximately 13,220 patients in 55 countries will be randomized (1:1:1 ratio) to receive UFH plus downstream eptifibatide (started pre-percutaneous coronary intervention and continued per label) or otamixaban (0.08 mg/kg intravenous bolus at randomization then 0.100 or 0.140 mg/kg per hour intravenous infusion). An interim analysis was performed after ≥1,969 patients per arm completed 7 days of follow-up and the Data Monitoring Committee selected 1 otamixaban dose (blinded to investigators) to be carried forward using a prespecified algorithm. The primary efficacy outcome is the composite of all-cause mortality or new MI through day 7. The primary safety outcome is thrombolysis in MI major or minor bleeding through day 7. Secondary outcomes include all-cause mortality, recurrent ischemia/infarction resulting in prolonged/recurrent hospitalization, periprocedural angiographic complications, and pharmacokinetic data in 6,000 patients.
  
  
  CONCLUSIONS
  The TAO trial will assess the clinical efficacy and safety of otamixaban in non-ST-segment elevation ACS with planned invasive strategy.
authors.affiliation: AP-HP, Hôpital Bichat, Paris, France. gabriel.steg@bch.aphp.fr
authors.forename: Philippe Gabriel
authors.initials: PG
authors.lastname: Steg
authors.forename: Shamir R
authors.initials: SR
authors.lastname: Mehta
authors.forename: Charles V
authors.initials: CV
authors.lastname: Pollack
authors.forename: Christoph
authors.initials: C
authors.lastname: Bode
authors.forename: Christophe
authors.initials: C
authors.lastname: Gaudin
authors.forename: Karen
authors.initials: K
authors.lastname: Fanouillere
authors.forename: Angele
authors.initials: A
authors.lastname: Moryusef
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Wiviott
authors.forename: Marc S
authors.initials: MS
authors.lastname: Sabatine
mesh_terms: D054058:Acute Coronary Syndrome / Q000150:complications / Q000188:drug therapy* / Q000401:mortality; D000293:Adolescent; D000328:Adult; D003497:Cyclic N-Oxides / Q000008:administration & dosage* / Q000009:adverse effects; D004311:Double-Blind Method; D004359:Drug Therapy, Combination; D000077542:Eptifibatide; D065427:Factor Xa Inhibitors; D006470:Hemorrhage / Q000209:etiology; D006493:Heparin / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D009203:Myocardial Infarction / Q000209:etiology; D010455:Peptides / Q000008:administration & dosage* / Q000009:adverse effects; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage*; D011725:Pyridines / Q000008:administration & dosage* / Q000009:adverse effects; D012107:Research Design; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D003497:Cyclic N-Oxides; D065427:Factor Xa Inhibitors; D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D011725:Pyridines; D006493:Heparin; D000077542:Eptifibatide; C435830:otamixaban