title: Evaluation of a new heparin agent in percutaneous coronary intervention: results of the phase 2 evaluation of M118 IN pErcutaNeous Coronary intErvention (EMINENCE) Trial.
abstract: BACKGROUND
  Factor Xa and factor IIa (thrombin) play roles in thrombotic complications after percutaneous coronary intervention. M118 is a novel low-molecular-weight heparin that has been rationally designed to capture the desired attributes of unfractionated heparin (UFH) and low-molecular-weight heparin: Potent activity against factor Xa and IIa, predictable pharmacokinetics after both intravenous and subcutaneous administration, ability to be monitored by use of point-of-care coagulation assays, and reversibility with protamine sulfate. We performed a phase 2 randomized trial to evaluate the safety and feasibility of M118 in the setting of elective percutaneous coronary intervention.
  
  
  RESULTS
  Overall, 503 patients undergoing elective percutaneous coronary intervention at 43 centers in the United States and Canada were randomized in an open-label fashion to 1 of 4 arms: UFH 70 U/kg, M118 50 IU/kg IV, M118 75 IU/kg IV, or M118 100 IU/kg IV. The primary outcome was the composite of death, myocardial infarction, repeat revascularization, stroke, thrombocytopenia, catheter thrombus, bailout use of glycoprotein IIb/IIIa inhibitor, or any bleeding through 30 days. The primary end point occurred in 31.1% of patients randomized to UFH and in 22.7%, 28.3%, and 30.1% of patients randomized to M118 50, 75, and 100 IU/kg, respectively. The primary analysis comparing the rates of the primary end points between the pooled M118 groups versus UFH demonstrated that M118 was noninferior to UFH at preventing percutaneous coronary intervention-related complications (28.4% pooled M118 arms versus 31.1% UFH). The adverse event profiles of M118 and UFH were comparable.
  
  
  CONCLUSIONS
  This phase 2 randomized trial demonstrates that M118 is well tolerated and feasible to use as an anticoagulant in patients undergoing elective percutaneous coronary intervention and forms the basis for further investigation of this agent in ischemic heart disease.
  
  
  BACKGROUND
  URL: http://www.clinicaltrials.gov. Unique identifier: NCT00543400.
authors.affiliation: Duke Clinical Research Institute, Durham, NC, USA. sunil.rao@duke.edu
authors.forename: Sunil V
authors.initials: SV
authors.lastname: Rao
authors.forename: Chiara
authors.initials: C
authors.lastname: Melloni
authors.forename: Shelley
authors.initials: S
authors.lastname: Myles-Dimauro
authors.forename: Samuel
authors.initials: S
authors.lastname: Broderick
authors.forename: Andrzej S
authors.initials: AS
authors.lastname: Kosinski
authors.forename: Neal S
authors.initials: NS
authors.lastname: Kleiman
authors.forename: Vladimír
authors.initials: V
authors.lastname: Dzavík
authors.forename: Jean Francois
authors.initials: JF
authors.lastname: Tanguay
authors.forename: Harish
authors.initials: H
authors.lastname: Chandna
authors.forename: Roger
authors.initials: R
authors.lastname: Gammon
authors.forename: Ernesto
authors.initials: E
authors.lastname: Rivera
authors.forename: John H
authors.initials: JH
authors.lastname: Alexander
authors.forename: Ian
authors.initials: I
authors.lastname: Fier
authors.forename: James
authors.initials: J
authors.lastname: Roach
authors.forename: Richard C
authors.initials: RC
authors.lastname: Becker
mesh_terms: D000368:Aged; D015906:Angioplasty, Balloon, Coronary; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D003324:Coronary Artery Disease / Q000401:mortality / Q000628:therapy*; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000401:mortality / Q000628:therapy; D013927:Thrombosis / Q000517:prevention & control*; D016896:Treatment Outcome
chemical_list: D000925:Anticoagulants; D006495:Heparin, Low-Molecular-Weight