使用抗内毒素的HA-1A人单克隆抗体治疗革兰氏阴性菌血症和感染性休克。一项随机、双盲、安慰剂对照试验。HA-1A脓毒症研究组。

Treatment of gram-negative bacteremia and septic shock with HA-1A human monoclonal antibody against endotoxin. A randomized, double-blind, placebo-controlled trial. The HA-1A Sepsis Study Group.

作者信息

Ziegler E J, Fisher C J, Sprung C L, Straube R C, Sadoff J C, Foulke G E, Wortel C H, Fink M P, Dellinger R P, Teng N N

机构信息

Department of Medicine, University of California, San Diego.

出版信息

N Engl J Med. 1991 Feb 14;324(7):429-36. doi: 10.1056/NEJM199102143240701.

DOI:10.1056/NEJM199102143240701

PMID:1988827

Abstract

BACKGROUND

HA-1A is a human monoclonal IgM antibody that binds specifically to the lipid A domain of endotoxin and prevents death in laboratory animals with gram-negative bacteremia and endotoxemia.

METHODS

To evaluate the efficacy and safety of HA-1A, we conducted a randomized, double-blind trial in patients with sepsis and a presumed diagnosis of gram-negative infection. The patients received either a single 100-mg intravenous dose of HA-1A (in 3.5 g of albumin) or placebo (3.5 g of albumin). Other interventions, including the administration of antibiotics and fluids, were not affected by the study protocol.

RESULTS

Of 543 patients with sepsis who were treated, 200 (37 percent) had gram-negative bacteremia as proved by blood culture. For the patients with gram-negative bacteremia followed to death or day 28, there were 45 deaths among the 92 recipients of placebo (49 percent) and 32 deaths among the 105 recipients of HA-1A (30 percent; P = 0.014). For the patients with gram-negative bacteremia and shock at entry, there were 27 deaths among the 47 recipients of placebo (57 percent) and 18 deaths among the 54 recipients of HA-1A (33 percent; P = 0.017). Analyses that stratified according to the severity of illness at entry showed improved survival with HA-1A treatment in both severely ill and less severely ill patients. Of the 196 patients with gram-negative bacteremia who were followed to hospital discharge or death, 45 of the 93 given placebo (48 percent) were discharged alive, as compared with 65 of the 103 treated with HA-1A (63 percent; P = 0.038). No benefit of treatment with HA-1A was demonstrated in the 343 patients with sepsis who did not prove to have gram-negative bacteremia. For all 543 patients with sepsis who were treated, the mortality rate was 43 percent among the recipients of placebo and 39 percent among those given HA-1A (P = 0.24). All patients tolerated HA-1A well, and no anti-HA-1A antibodies were detected.

CONCLUSIONS

HA-1A is safe and effective for the treatment of patients with sepsis and gram-negative bacteremia.

摘要

背景

HA - 1A是一种人源单克隆IgM抗体，它能特异性结合内毒素的脂质A结构域，并可防止革兰氏阴性菌血症和内毒素血症实验动物的死亡。

方法

为评估HA - 1A的疗效和安全性，我们对脓毒症且推测为革兰氏阴性菌感染的患者进行了一项随机双盲试验。患者接受单次100毫克静脉注射剂量的HA - 1A（溶于3.5克白蛋白）或安慰剂（3.5克白蛋白）。其他干预措施，包括抗生素和液体的使用，不受研究方案影响。

结果

在接受治疗的543例脓毒症患者中，200例（37%）血培养证实有革兰氏阴性菌血症。对于革兰氏阴性菌血症且随访至死亡或第28天的患者，92例接受安慰剂治疗的患者中有45例死亡（49%），105例接受HA - 1A治疗的患者中有32例死亡（30%；P = 0.014）。对于入院时伴有革兰氏阴性菌血症和休克的患者，47例接受安慰剂治疗的患者中有27例死亡（57%），54例接受HA - 1A治疗的患者中有18例死亡（33%；P = 0.017）。根据入院时疾病严重程度分层的分析显示，HA - 1A治疗对重症和轻症患者的生存率均有改善。在随访至出院或死亡的196例革兰氏阴性菌血症患者中，93例接受安慰剂治疗的患者中有45例（48%）存活出院，而103例接受HA - 1A治疗的患者中有65例（63%）存活出院（P = 0.038）。在343例未证实有革兰氏阴性菌血症的脓毒症患者中，未显示HA - 1A治疗有任何益处。对于所有543例接受治疗的脓毒症患者，安慰剂组的死亡率为43%，HA - 1A组为39%（P = 0.24）。所有患者对HA - 1A耐受性良好，未检测到抗HA - 1A抗体。