Lazar Harold L, Keilani Taha, Fitzgerald Carmel A, Shapira Oz M, Hunter Curtis T, Shemin Richard J, Marsh Henry C, Ryan Una S
Department of Cardiothoracic Surgery, Boston University School of Medicine and the Boston Medical Center, 88 East Newton Street, Suite B402, Boston, MA 02118, USA.
Circulation. 2007 Sep 11;116(11 Suppl):I83-8. doi: 10.1161/CIRCULATIONAHA.106.677914.
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).
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).
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.
TP10是一种在体外循环（CPB）期间有效抑制补体激活的药物，已显示可显著降低接受心脏手术的高危男性患者的死亡和心肌梗死（MI）发生率。然而，由于所研究的女性数量有限，TP10在女性中的作用尚不明确。为了研究性别效应的可能性，开展了这项2期多中心试验，以确定TP10是否也能在接受CPB心脏手术的更大样本量高危女性中限制缺血性损伤。
这项前瞻性、双盲、安慰剂对照、多中心试验纳入了297例高危（急诊手术、冠状动脉搭桥术+瓣膜手术、再次手术、射血分数<30%）女性患者，她们被随机分为两组，在手术前接受30分钟静脉输注5mg/kg剂量的TP10（n=150）或安慰剂（n=147）。主要终点是术后28天的死亡或MI发生率。通过CPB期间及之后的CH50和SC5b-9水平评估补体激活情况。TP10耐受性良好，两组的安全性概况无差异。尽管TP10有效地抑制了补体激活（CPB后2小时CH50（平均+标准差，相对于基线的变化百分比）安慰剂组为50±17%，TP10组为4±14%；P=0.0001；SC5b-9（ng/mL）安慰剂组为917±1067，TP10组为204±79；P=0.0001），但两组之间的主要终点无差异（安慰剂组为17%，TP10组为21%；P=0.2550）。
TP10的益处似乎与性别相关。在接受CPB心脏手术的高危女性患者中，除补体激活外的其他机制可能是心肌损伤的原因。
