PMID- 17502577
OWN - NLM
STAT- MEDLINE
DCOM- 20070604
LR  - 20171116
IS  - 1524-4539 (Electronic)
IS  - 0009-7322 (Linking)
VI  - 115
IP  - 20
DP  - 2007 May 22
TI  - Randomized, double-blind, dose-ranging study of otamixaban, a novel, parenteral, 
      short-acting direct factor Xa inhibitor, in percutaneous coronary intervention: 
      the SEPIA-PCI trial.
PG  - 2642-51
AB  - BACKGROUND: The optimal anticoagulant regimen for percutaneous coronary 
      intervention (PCI) remains to be determined. Otamixaban, a selective and direct 
      inhibitor of factor Xa, was investigated in patients undergoing nonurgent 
      percutaneous coronary intervention. METHODS AND RESULTS: In this double-blind, 
      double-dummy, parallel-group, dose-ranging trial, 947 patients were randomly 
      assigned to either 1 of 5 weight-adjusted otamixaban regimens or weight-adjusted 
      unfractionated heparin (UFH) before percutaneous coronary intervention. The 
      primary end points were change in prothrombin fragments 1+2 (F1+2), and 
      anti-factor Xa activity. The main secondary end points were Thrombolysis In 
      Myocardial Infarction (TIMI) bleeding at day 3 or hospital discharge (whichever 
      came first) and 30-day ischemic events. The median change in F1+2 from baseline 
      to the end of infusion was greater with the highest otamixaban dose compared with 
      UFH (-0.3 versus -0.2 ng/mL, P=0.008). Anti-factor Xa levels were 65, 155, 393, 
      571, and 691 ng/mL with otamixaban doses 1 to 5, respectively. Significant TIMI 
      bleeding (major or minor) occurred in 2.0%, 1.9%, 3.8%, 3.9%, and 2.6% of 
      patients receiving otamixaban doses 1 to 5, respectively, and in 3.8% of patients 
      receiving UFH. Four TIMI major bleeds were observed. Ischemic events occurred in 
      5.8%, 7.1%, 3.8%, 2.5%, and 5.1% of patients receiving otamixaban doses 1 to 5, 
      respectively, and in 5.6% of patients receiving UFH. CONCLUSIONS: Otamixaban 
      reduced F1+2 significantly more than UFH at the highest dose regimen, whereas no 
      significant difference in the incidence of TIMI bleeding was observed between the 
      otamixaban and UFH groups. These results set the stage for adequately powered 
      clinical outcome trials of selective direct factor Xa inhibition in patients with 
      acute coronary syndromes.
FAU - Cohen, Marc
AU  - Cohen M
AD  - Division of Cardiology, Newark Beth Israel Medical Center, 201 Lyons Ave, Newark, 
      NJ 07112, USA. marcohen@sbhcs.com
FAU - Bhatt, Deepak L
AU  - Bhatt DL
FAU - Alexander, John H
AU  - Alexander JH
FAU - Montalescot, Gilles
AU  - Montalescot G
FAU - Bode, Christoph
AU  - Bode C
FAU - Henry, Timothy
AU  - Henry T
FAU - Tamby, Jean-Francois
AU  - Tamby JF
FAU - Saaiman, Jan
AU  - Saaiman J
FAU - Simek, Stanislas
AU  - Simek S
FAU - De Swart, Johannes
AU  - De Swart J
CN  - SEPIA-PCI Trial Investigators
LA  - eng
PT  - Clinical Trial, Phase II
PT  - Comparative Study
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20070514
PL  - United States
TA  - Circulation
JT  - Circulation
JID - 0147763
RN  - 0 (Cyclic N-Oxides)
RN  - 0 (Peptide Fragments)
RN  - 0 (Protein Precursors)
RN  - 0 (Pyridines)
RN  - 72270-84-9 (prothrombin fragment 1)
RN  - 78768-79-3 (prothrombin fragment 2)
RN  - 9000-94-6 (Antithrombin III)
RN  - 9001-26-7 (Prothrombin)
RN  - S173RED00L (otamixaban)
SB  - IM
MH  - Aged
MH  - *Angioplasty, Balloon, Coronary
MH  - Antithrombin III/*administration & dosage/adverse effects/metabolism
MH  - Coronary Disease/mortality/*therapy
MH  - Cyclic N-Oxides/*administration & dosage/adverse effects
MH  - Dose-Response Relationship, Drug
MH  - Double-Blind Method
MH  - Female
MH  - Hemorrhage/chemically induced/epidemiology
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Myocardial Infarction
MH  - Partial Thromboplastin Time
MH  - Peptide Fragments/blood
MH  - Protein Precursors/blood
MH  - Prothrombin
MH  - Pyridines/*administration & dosage/adverse effects
EDAT- 2007/05/16 09:00
MHDA- 2007/06/05 09:00
CRDT- 2007/05/16 09:00
PHST- 2007/05/16 09:00 [pubmed]
PHST- 2007/06/05 09:00 [medline]
PHST- 2007/05/16 09:00 [entrez]
AID - CIRCULATIONAHA.106.653428 [pii]
AID - 10.1161/CIRCULATIONAHA.106.653428 [doi]
PST - ppublish
SO  - Circulation. 2007 May 22;115(20):2642-51. doi: 10.1161/CIRCULATIONAHA.106.653428. 
      Epub 2007 May 14.