Soluble human complement receptor 1 limits ischemic damage in cardiac surgery patients at high risk requiring cardiopulmonary bypass

Circulation. 2004 Sep 14;110(11 Suppl 1):II274-9. doi: 10.1161/01.CIR.0000138315.99788.eb.


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.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Cardiac Surgical Procedures* / mortality
  • Cardiopulmonary Bypass / adverse effects*
  • Complement Activation / drug effects*
  • Complement C3a / biosynthesis
  • Complement Membrane Attack Complex / biosynthesis
  • Double-Blind Method
  • Female
  • Humans
  • Infections / epidemiology
  • Injections, Intravenous
  • Intra-Aortic Balloon Pumping / statistics & numerical data
  • Length of Stay / statistics & numerical data
  • Male
  • Middle Aged
  • Myocardial Infarction / diagnosis
  • Myocardial Infarction / epidemiology
  • Myocardial Infarction / etiology
  • Myocardial Ischemia / etiology
  • Myocardial Ischemia / immunology
  • Myocardial Ischemia / prevention & control*
  • Prospective Studies
  • Receptors, Complement / administration & dosage
  • Receptors, Complement / therapeutic use*
  • Sex Factors
  • Solubility
  • Treatment Outcome


  • Complement Membrane Attack Complex
  • Receptors, Complement
  • soluble complement inhibitor 1
  • Complement C3a