Otamixaban for the treatment of patients with non-ST-elevation acute coronary syndromes (SEPIA-ACS1 TIMI 42): a randomised, double-blind, active-controlled, phase 2 trial.
Abstract | BACKGROUND: METHODS: In this double-blind, phase 2 trial undertaken in 196 sites in 36 countries, 3241 patients with non-ST-elevation acute coronary syndromes were randomly assigned via a central, telephone-based interactive voice response system to one of five doses of otamixaban (0.08 mg/kg bolus followed by infusions of 0.035 [n=125], 0.070 [676], 0.105 [662], 0.140 [658], or 0.175 [671] mg/kg/h) or to a control of unfractionated heparin (60 IU/kg intravenous bolus followed by an infusion of 12 IU/kg/h) plus eptifibatide (180 microg/kg intravenous bolus followed by an infusion of 1.0-2.0 microg/kg/min [n=449]). Both investigators and patients were unaware of treatment allocation. Enrolment into the lowest dose group was stopped early at the recommendation of the Data Monitoring Committee. The primary efficacy endpoint was a composite of death, myocardial infarction, urgent revascularisation, or bailout glycoprotein IIb/IIIa inhibitor use up to 7 days. The primary safety endpoint was TIMI major or minor bleeding not related to coronary-artery bypass grafting. Efficacy analyses were by intention to treat; safety analyses were in treated patients. This study is registered with ClinicalTrials.gov, number NCT00317395. FINDINGS: Rates of the primary efficacy endpoint in the five otamixaban doses were 7.2% (nine of 125) with 0.035 mg/kg/h, 4.6% (31/676) with 0.070 mg/kg/h, 3.8% (25/662) with 0.105 mg/kg/h, 3.6% (24/658) with 0.140 mg/kg/h, and 4.3% (29/671) with 0.175 mg/kg/h (p=0.34 for trend). In the control group, the rate was 6.2% (28/449), yielding relative risks for the five otamixaban doses of 1.16 (95% CI 0.56-2.38), 0.74 (0.45-1.21), 0.61 (0.36-1.02), 0.58 (0.34-1.00), and 0.69 (0.42-1.15), respectively. Rates of the primary safety endpoint in the five otamixaban doses were 1.6% (two of 122), 1.6% (11/669), 3.1% (20/651), 3.4% (22/651), and 5.4% (36/664), respectively (p=0.0001 for trend); the rate in the control group was 2.7% (12/448). INTERPRETATION: FUNDING: Sanofi-Aventis.
|
Authors | Marc S Sabatine, Elliott M Antman, Petr Widimsky, Iftikhar O Ebrahim, Robert G Kiss, André Saaiman, Rostislav Polasek, Charles F Contant, Carolyn H McCabe, Eugene Braunwald |
Journal | Lancet (London, England)
(Lancet)
Vol. 374
Issue 9692
Pg. 787-95
(Sep 05 2009)
ISSN: 1474-547X [Electronic] England |
PMID | 19717184
(Publication Type: Clinical Trial, Phase II, Comparative Study, Journal Article, Multicenter Study, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
|
Chemical References |
- Anticoagulants
- Cyclic N-Oxides
- Peptides
- Platelet Aggregation Inhibitors
- Pyridines
- Heparin
- Eptifibatide
- otamixaban
|
Topics |
- Acute Coronary Syndrome
(complications, diagnosis, drug therapy, mortality)
- Aged
- Angioplasty, Balloon, Coronary
- Anticoagulants
(therapeutic use)
- Coronary Angiography
- Cyclic N-Oxides
(pharmacology, therapeutic use)
- Dose-Response Relationship, Drug
- Double-Blind Method
- Drug Therapy, Combination
- Eptifibatide
- Female
- Follow-Up Studies
- Hemorrhage
(chemically induced)
- Heparin
(therapeutic use)
- Humans
- Infusions, Intravenous
- Injections, Intravenous
- Kaplan-Meier Estimate
- Male
- Middle Aged
- Peptides
(therapeutic use)
- Platelet Aggregation Inhibitors
(therapeutic use)
- Pyridines
(pharmacology, therapeutic use)
- Safety
- Treatment Outcome
|
|
Join CureHunter, for free Research Interface BASIC access!
Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease.
Find out why thousands of doctors, pharma researchers and patient activists
around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!
|