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.

Abstract

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.

• Authors: Marc Cohen, Deepak L Bhatt, John H Alexander, Gilles Montalescot, Christoph Bode, Timothy Henry, Jean-Francois Tamby, Jan Saaiman, Stanislas Simek, Johannes De Swart, SEPIA-PCI Trial Investigators
• Journal: Circulation (Circulation) Vol. 115 Issue 20 Pg. 2642-51 (May 22 2007) ISSN: 1524-4539 [Electronic] United States
• PMID: 17502577 (Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Cyclic N-Oxides
• Peptide Fragments
• Protein Precursors
• Pyridines
• prothrombin fragment 1
• prothrombin fragment 2
• Antithrombin III
• Prothrombin
• otamixaban

Topics

• Aged
• Angioplasty, Balloon, Coronary
• Antithrombin III (administration & dosage, adverse effects, metabolism)
• Coronary Disease (mortality, therapy)
• Cyclic N-Oxides (administration & dosage, adverse effects)
• Dose-Response Relationship, Drug
• Double-Blind Method
• Female
• Hemorrhage (chemically induced, epidemiology)
• Humans
• Male
• Middle Aged
• Myocardial Infarction
• Partial Thromboplastin Time
• Peptide Fragments (blood)
• Protein Precursors (blood)
• Prothrombin
• Pyridines (administration & dosage, adverse effects)