Abstract 3349: Beneficial Effects of Complement Inhibition with TP10 During Cardiac Surgery: Is There a Gender Difference?
TP10, a potent inhibitor of complement activation during cardiopulmonary bypass (CPB), has been shown to significantly reduce the incidence of death and 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. In order to examine the possibility of a gender effect, this phase II multicenter trial was undertaken to determine whether TP10 would also limit ischemic damage in a large group of high risk females undergoing cardiac surgery on CPB. This prospective, placebo-controlled, multicenter 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 thirty minute IV infusion prior to surgery. The primary endpoint was the incidence of death or MI at 28 days following surgery. Complement activation was assessed by levels of CH50 and SC5b-9 during CPB. Results are expressed as the mean+/- standard deviation and the actual occurrences. TP10 was well tolerated and there were no differences in the safety profiles of the two groups. Although TP10 effectively suppressed complement activation,there was no difference in the primary endpoint between the groups. This suggests that the benefits of TP10 are gender related and that mechanisms other than complement activation may be responsible for myocardial injury in high risk female patients during cardiac surgery on CPB.