Armstrong Paul W, Granger Christopher B, Adams Peter X, Hamm Christian, Holmes David, O'Neill William W, Todaro Thomas G, Vahanian Alec, Van de Werf Frans
University of Alberta, Edmonton, Alberta, T6G 2H7 Canada.
JAMA. 2007 Jan 3;297(1):43-51. doi: 10.1001/jama.297.1.43.
Reperfusion with percutaneous transluminal coronary intervention (PCI) is effective at improving outcomes in patients with acute ST-elevation myocardial infarction (STEMI). However, in patients without prompt reestablishment of brisk coronary flow and tissue perfusion, mortality remains high, providing an opportunity for novel treatments, including anti-inflammatory agents.
To evaluate the effectiveness of pexelizumab, a humanized monoclonal antibody that binds the C5 component of complement, as an adjunct to PCI in improving 30-day mortality from STEMI.
DESIGN, SETTING, AND PATIENTS: This trial was a prospective, multicenter, double-blind, placebo-controlled, phase 3 study of the intravenous administration of pexelizumab in conjunction with primary PCI in STEMI with prespecified high-risk electrocardiographic findings. The trial was intended to enroll 8500 patients, but in conjunction with the US Food and Drug Administration enrollment was modified to 5745 patients presenting from 296 hospitals in 17 countries from July 13, 2004, to May 11, 2006.
Two thousand eight hundred eighty-five patients were randomly assigned to receive placebo and 2860 to receive pexelizumab given as a 2-mg/kg intravenous bolus prior to PCI followed by 0.05-mg/kg per hour infusion over the subsequent 24 hours. Patients were randomized within 6 hours of symptom onset.
The primary end point was all-cause mortality through day 30. Secondary end points were death through day 90 and the composite of death, cardiogenic shock, or congestive heart failure through days 30 and 90.
No difference in mortality through day 30 was observed between the pexelizumab and placebo treatment groups, with 116 patients (4.06%) and 113 patients (3.92%) who died in the respective groups (hazard ratio [HR], 1.04; 95% confidence interval [CI], 0.80-1.35; log-rank P = .78). The composite end points of death, shock, or heart failure were also similar with 257 patients (8.99%) receiving pexelizumab and 265 patients (9.19%) receiving placebo at 30 days (HR, 0.98; 95% CI, 0.83-1.16; P = .81) and 293 patients (10.24%) receiving pexelizumab and 293 patients (10.16%) receiving placebo at 90 days (HR, 1.01; 95% CI, 0.86-1.19; P = .91).
In this large clinical trial of patients treated with primary PCI for STEMI, mortality was low and unaffected by administration of pexelizumab.
clinicaltrials.gov Identifier: NCT00091637.
经皮冠状动脉腔内血管成形术（PCI）再灌注治疗对改善急性ST段抬高型心肌梗死（STEMI）患者的预后有效。然而，对于未能迅速重建冠脉血流和组织灌注的患者，死亡率仍然很高，这为包括抗炎药物在内的新治疗方法提供了机会。
评估人源化单克隆抗体培塞利珠单抗（一种结合补体C5成分的药物）作为PCI辅助治疗改善STEMI患者30天死亡率的有效性。
设计、地点和患者：本试验是一项前瞻性、多中心、双盲、安慰剂对照的3期研究，在有预先指定的高危心电图表现的STEMI患者中，将培塞利珠单抗静脉给药与直接PCI联合应用。该试验计划招募8500例患者，但经美国食品药品监督管理局同意，于2004年7月13日至2006年5月11日，将入组患者改为来自17个国家296家医院的5745例患者。
2885例患者被随机分配接受安慰剂，2860例患者在PCI术前静脉推注2mg/kg培塞利珠单抗，随后在接下来的24小时内以每小时0.05mg/kg的速度输注。患者在症状发作6小时内随机分组。
主要终点是至30天的全因死亡率。次要终点是至90天的死亡率以及至30天和90天的死亡、心源性休克或充血性心力衰竭的复合终点。
培塞利珠单抗治疗组和安慰剂治疗组在30天死亡率方面未观察到差异，两组分别有116例患者（4.06%）和113例患者（3.92%）死亡（风险比[HR]，1.04；95%置信区间[CI]，0.80 - 1.35；对数秩检验P = 0.78）。死亡、休克或心力衰竭的复合终点也相似，30天时接受培塞利珠单抗的患者有257例（8.99%），接受安慰剂的患者有265例（9.19%）（HR，0.98；95% CI，0.83 - 1.16；P = 0.81）；90天时接受培塞利珠单抗的患者有293例（10.24%），接受安慰剂的患者有293例（10.16%）（HR，1.01；95% CI，0.86 - 1.19；P = 0.91）。
在这项针对接受直接PCI治疗的STEMI患者的大型临床试验中，死亡率较低，且不受培塞利珠单抗给药的影响。
美国国立医学图书馆临床试验注册中心标识符：NCT00091637。
