title: Soluble human complement receptor 1 limits ischemic damage in cardiac surgery patients at high risk requiring cardiopulmonary bypass.
abstract: BACKGROUND
  This study was undertaken to determine whether soluble human complement receptor type 1 (TP10), a potent inhibitor of complement activation, would reduce morbidity and mortality in high-risk patients undergoing cardiac surgery on cardiopulmonary bypass (CPB).
  
  
  METHODS
  This was a randomized multicenter, prospective, placebo-controlled, double-blind study in which 564 high-risk patients undergoing cardiac surgery on CPB received an intravenous bolus of TP10 (1, 3, 5, 10 mg/kg) or placebo immediately before CPB. The primary endpoint was the composite events of death, myocardial infarction (MI), prolonged (> or =24 hours) intra-aortic balloon pump support (IABP), and prolonged intubation.
  
  
  RESULTS
  TP10 significantly inhibited complement activity after 10 to 15 minutes of CPB and this inhibition persisted for 3 days postoperatively. However, there was no difference in the primary endpoint between the 2 groups (33.7% placebo versus 31.4% TP10; P=0.31). The primary composite endpoint was, however, reduced in all male TP10 patients by 30% (P=0.025). TP10 reduced the incidence of death or MI in males by 36% (P=0.026), the incidence of death or MI in CABG males by 43% (P=0.043) and the need for prolonged IABP support in male CABG and valve patients by 100% (P=0.019). There was, however, no improvement seen in female TP10 patients. There were no significant differences in adverse events between the groups.
  
  
  CONCLUSIONS
  TP10 effectively inhibits complement activation during CPB; however, this was not associated with an improvement in the primary endpoint of the study. Nevertheless, TP10 did significantly decrease the incidence of mortality and MI in male patients.
authors.affiliation: Department of Cardiothoracic Surgery, Boston University School of Medicine and Boston Medical Center, Boston, Mass 02118, USA. harold.lazar@bmc.org
authors.forename: Harold L
authors.initials: HL
authors.lastname: Lazar
authors.forename: Paula M
authors.initials: PM
authors.lastname: Bokesch
authors.forename: Frederick
authors.initials: F
authors.lastname: van Lenta
authors.forename: Carmel
authors.initials: C
authors.lastname: Fitzgerald
authors.forename: Constance
authors.initials: C
authors.lastname: Emmett
authors.forename: Henry C
authors.initials: HC
authors.lastname: Marsh
authors.forename: Una
authors.initials: U
authors.lastname: Ryan
mesh_terms: D000368:Aged; D006348:Cardiac Surgical Procedures / Q000401:mortality; D002315:Cardiopulmonary Bypass / Q000009:adverse effects*; D003167:Complement Activation / Q000187:drug effects*; D015926:Complement C3a / Q000096:biosynthesis; D015938:Complement Membrane Attack Complex / Q000096:biosynthesis; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007239:Infections / Q000453:epidemiology; D007275:Injections, Intravenous; D007423:Intra-Aortic Balloon Pumping / Q000706:statistics & numerical data; D007902:Length of Stay / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000453:epidemiology / Q000209:etiology; D017202:Myocardial Ischemia / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D011446:Prospective Studies; D011951:Receptors, Complement / Q000008:administration & dosage / Q000627:therapeutic use*; D012737:Sex Factors; D012995:Solubility; D016896:Treatment Outcome
chemical_list: D015938:Complement Membrane Attack Complex; D011951:Receptors, Complement; C082885:soluble complement inhibitor 1; D015926:Complement C3a