PMID- 20368520 OWN - NLM STAT- MEDLINE DCOM- 20100513 LR - 20101118 IS - 1524-4539 (Electronic) IS - 0009-7322 (Linking) VI - 121 IP - 15 DP - 2010 Apr 20 TI - Evaluation of a new heparin agent in percutaneous coronary intervention: results of the phase 2 evaluation of M118 IN pErcutaNeous Coronary intErvention (EMINENCE) Trial. PG - 1713-21 LID - 10.1161/CIRCULATIONAHA.109.913277 [doi] AB - 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. METHODS AND 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. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00543400. FAU - Rao, Sunil V AU - Rao SV AD - Duke Clinical Research Institute, Durham, NC, USA. sunil.rao@duke.edu FAU - Melloni, Chiara AU - Melloni C FAU - Myles-Dimauro, Shelley AU - Myles-Dimauro S FAU - Broderick, Samuel AU - Broderick S FAU - Kosinski, Andrzej S AU - Kosinski AS FAU - Kleiman, Neal S AU - Kleiman NS FAU - Dzavik, Vladimir AU - Dzavik V FAU - Tanguay, Jean Francois AU - Tanguay JF FAU - Chandna, Harish AU - Chandna H FAU - Gammon, Roger AU - Gammon R FAU - Rivera, Ernesto AU - Rivera E FAU - Alexander, John H AU - Alexander JH FAU - Fier, Ian AU - Fier I FAU - Roach, James AU - Roach J FAU - Becker, Richard C AU - Becker RC CN - EMINENCE Investigators LA - eng SI - ClinicalTrials.gov/NCT00543400 PT - Clinical Trial, Phase II PT - Journal Article PT - Multicenter Study PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't DEP - 20100405 PL - United States TA - Circulation JT - Circulation JID - 0147763 RN - 0 (Anticoagulants) RN - 0 (Heparin, Low-Molecular-Weight) SB - IM MH - Aged MH - *Angioplasty, Balloon, Coronary MH - Anticoagulants/*administration & dosage/adverse effects MH - Coronary Artery Disease/mortality/*therapy MH - Female MH - Heparin, Low-Molecular-Weight/*administration & dosage/adverse effects MH - Humans MH - Injections, Intravenous MH - Male MH - Middle Aged MH - Myocardial Infarction/mortality/therapy MH - Thrombosis/*prevention & control MH - Treatment Outcome FIR - Rao, Sunil V IR - Rao SV FIR - Melloni, Chiara IR - Melloni C FIR - Becker, Richard C IR - Becker RC FIR - Kleiman, Neal S IR - Kleiman NS FIR - Dzavik, Vladimir IR - Dzavik V FIR - Tanguay, Jean Francois IR - Tanguay JF FIR - Cohen, Marc S IR - Cohen MS FIR - Kimmelstiel, Carey IR - Kimmelstiel C FIR - Fier, Ian IR - Fier I FIR - Roach, James IR - Roach J FIR - Lopes, Renato D IR - Lopes RD FIR - Hester, Willie IR - Hester W FIR - Mehta, Rajendra H IR - Mehta RH FIR - Bushnell, Cheryl IR - Bushnell C FIR - Mahaffey, Kenneth W IR - Mahaffey KW FIR - Roe, Matthew T IR - Roe MT FIR - Tricoci, Pierluigi IR - Tricoci P FIR - Wang, Tracy Y IR - Wang TY FIR - Melloni, Chiara IR - Melloni C FIR - Alexander, John H IR - Alexander JH FIR - Hernandez, Adrian F IR - Hernandez AF FIR - Al-Khatib, Sana IR - Al-Khatib S FIR - Felker, G Michael IR - Felker GM FIR - Gharacholou, S Michael IR - Gharacholou SM FIR - Newby, L Kristin IR - Newby LK FIR - Szczech, Lynda IR - Szczech L FIR - Vergara-Jimenez, Jennifer IR - Vergara-Jimenez J FIR - Marso, Steve P IR - Marso SP FIR - Ragosta, Michael IR - Ragosta M FIR - Cooper, Michael David IR - Cooper MD FIR - Rossi, Joseph IR - Rossi J FIR - Cohen, Mauricio G IR - Cohen MG FIR - Douglas, John S IR - Douglas JS FIR - Yakubov, Steven J IR - Yakubov SJ FIR - Hamdalla, Hussam IR - Hamdalla H FIR - Hermiller, James B IR - Hermiller JB FIR - Greenbaum, Adam IR - Greenbaum A FIR - Lim, Michael J IR - Lim MJ FIR - Gammon, Roger S IR - Gammon RS FIR - Kleiman, Neal S IR - Kleiman NS FIR - Walder, James S IR - Walder JS FIR - Malik, Amir Z IR - Malik AZ FIR - Nathan, Sandeep IR - Nathan S FIR - Ladley, Herbert D IR - Ladley HD FIR - Singh, Vibhuti N IR - Singh VN FIR - Vora, Kishor N IR - Vora KN FIR - Rosenberg, Michael IR - Rosenberg M FIR - Christy, George IR - Christy G FIR - Welsh, Robert C IR - Welsh RC FIR - Kutryk, Michael IR - Kutryk M FIR - Dzavik, Vladimir IR - Dzavik V FIR - Fung, Anthony Y IR - Fung AY FIR - Strauss, Bradley H IR - Strauss BH FIR - Gurm, Hitinder S IR - Gurm HS FIR - Dobies, David IR - Dobies D FIR - Neustel, Mark IR - Neustel M FIR - Hassinger, Nancy IR - Hassinger N FIR - Rivera, Ernesto IR - Rivera E FIR - Schaer, Gary L IR - Schaer GL FIR - Zenni, Martin 2nd IR - Zenni M 2nd FIR - Tanguay, Jean Francois IR - Tanguay JF FIR - Labinaz, Mario IR - Labinaz M FIR - Landau, Andre J IR - Landau AJ FIR - Albirini, Abdulhay IR - Albirini A FIR - Chandna, Harish IR - Chandna H FIR - Chandrashekhar, Yellapragada IR - Chandrashekhar Y FIR - Puri, Sanjeev IR - Puri S FIR - Uretsky, Barry IR - Uretsky B FIR - Bissett, Joe K IR - Bissett JK FIR - Minisi, Anthony IR - Minisi A FIR - Henderson, David A IR - Henderson DA FIR - Allaqaband, Suhail IR - Allaqaband S FIR - Shoultz, Charles Albert 3rd IR - Shoultz CA 3rd FIR - Dippel, Eric IR - Dippel E EDAT- 2010/04/07 06:00 MHDA- 2010/05/14 06:00 CRDT- 2010/04/07 06:00 PHST- 2010/04/07 06:00 [entrez] PHST- 2010/04/07 06:00 [pubmed] PHST- 2010/05/14 06:00 [medline] AID - CIRCULATIONAHA.109.913277 [pii] AID - 10.1161/CIRCULATIONAHA.109.913277 [doi] PST - ppublish SO - Circulation. 2010 Apr 20;121(15):1713-21. doi: 10.1161/CIRCULATIONAHA.109.913277. Epub 2010 Apr 5.