title: Beneficial effects of complement inhibition with soluble complement receptor 1 (TP10) during cardiac surgery: is there a gender difference?
abstract: BACKGROUND
  TP10, a potent inhibitor of complement activation during cardiopulmonary bypass (CPB) has been shown to significantly reduce the incidence of death and myocardial infarction (MI) in high-risk male patients undergoing cardiac surgery. However, the effect of TP10 in females was undefined because of the limited number of females studied. To examine the possibility of a gender effect, this phase 2 multi-center trial was undertaken to determine whether TP10 would also limit ischemic damage in a larger sample size of high-risk females undergoing cardiac surgery on cardiopulmonary bypass (CPB).
  
  
  RESULTS
  This prospective, double-blind, placebo-controlled, multi-center trial involved 297 high-risk (urgent surgery, CABG + Valve, reoperations, ejection fraction <30%) female patients randomized to receive a 5 mg/kg dose of TP10 (n=150) or placebo (n=147) as a 30-minute intravenous infusion before surgery. The primary end point was the incidence of death or MI at 28 days after surgery. Complement activation was assessed by levels of CH50 and SC5b-9 during and after CPB. TP10 was well tolerated and there were no differences in the safety profiles of the 2 groups. Although TP10 effectively suppressed complement activation (at 2 hours after CPB CH50 (mean+SD % change from baseline) 50+/-17% placebo versus 4+/-14% TP10; P=0.0001; SC5b-9 (ng/mL) 917+/-1067 placebo versus 204+/-79 TP10; P=0.0001), there was no difference in the primary end point between the groups (17% placebo versus 21% TP10; P=0.2550).
  
  
  CONCLUSIONS
  The benefits of TP10 appear to be gender-related. and mechanisms other than complement activation may be responsible for myocardial injury in high-risk female patients during cardiac surgery on CPB.
authors.affiliation: Department of Cardiothoracic Surgery, Boston University School of Medicine and the Boston Medical Center, 88 East Newton Street, Suite B402, Boston, MA 02118, USA. harold.lazar@bmc.org
authors.forename: Harold L
authors.initials: HL
authors.lastname: Lazar
authors.forename: Taha
authors.initials: T
authors.lastname: Keilani
authors.forename: Carmel A
authors.initials: CA
authors.lastname: Fitzgerald
authors.forename: Oz M
authors.initials: OM
authors.lastname: Shapira
authors.forename: Curtis T
authors.initials: CT
authors.lastname: Hunter
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Shemin
authors.forename: Henry C
authors.initials: HC
authors.lastname: Marsh
authors.forename: Una S
authors.initials: US
authors.lastname: Ryan
mesh_terms: D000368:Aged; D006348:Cardiac Surgical Procedures / Q000379:methods; D003165:Complement System Proteins / Q000378:metabolism*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011951:Receptors, Complement / Q000627:therapeutic use*; D012727:Sex Characteristics
chemical_list: D011951:Receptors, Complement; C082885:soluble complement inhibitor 1; D003165:Complement System Proteins