A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis
A randomized, blinded, multicenter trial of lipid-associated amphotericin B alone versus in combination with an antibody-based inhibitor of heat shock protein 90 in patients with invasive candidiasis
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DOI：
10.1086/503428
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发表时间：
2006-05-15
影响因子：
11.8
通讯作者：
Matthews, R
中科院分区：
文献类型：
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作者：
Pachl, J;Svoboda, P;Matthews, R
背景Mycograb（NeuTec Pharma）是一种针对热休克蛋白90的人重组单克隆抗体，在实验室研究中，其被揭示与白曲霉素B针对广谱念珠菌属物种具有协同作用。进行了一项双盲、随机研究，以确定在培养证实的侵袭性念珠菌病患者中，脂质相关的阿替霉素B联合Mycograb是否优于阿替霉素B联合安慰剂。患者接受脂质相关制剂阿替霉素B加5天疗程的Mycograb或安慰剂，并根据念珠菌属（白色念珠菌与非白色念珠菌属）进行分层。入选标准包括入组试验时活动性感染的临床证据，以及研究治疗开始后3天内来自临床显著部位的标本培养物上念珠菌属生长。主要疗效变量为第10天的总体治疗反应（临床和真菌学消退）。在从欧洲和美国入组的139例患者中，117例被纳入改良的意向治疗人群。与Mycograb联合治疗组的56例患者中的47例（84%）相比，阿朴霉素B组的61例患者中的29例（48%）在第10天获得了完全的总体缓解（比值比[OR]，5.8; 95%置信区间[CI]，2.41 - 13.79;）。还符合以下疗效标准：临床应答（52% vs. 86%; OR，5.4; 95% CI，2.21 - 13.39; P <.001），真菌学应答（54% vs. 89%; OR，7.1; 95% CI，2.64 - 18.94; P <.001），（18%比4%; OR，0.2; 95%CI，0.04 - 0.80; P = 0.025），以及培养确认的感染清除率（风险比，2.3; 95%CI，1.4 - 3.8; P = 0.001）。Mycograb的耐受性良好。Mycograb联合脂质相关的白念珠菌素B治疗侵袭性念珠菌病患者的临床和培养结果均得到证实。
Background. Mycograb (NeuTec Pharma) is a human recombinant monoclonal antibody against heat shock protein 90 that, in laboratory studies, was revealed to have synergy with amphotericin B against a broad spectrum of Candida species.Methods. A double-blind, randomized study was conducted to determine whether lipid-associated amphotericin B plus Mycograb was superior to amphotericin B plus placebo in patients with culture-confirmed invasive candidiasis. Patients received a lipid-associated formulation of amphotericin B plus a 5-day course of Mycograb or placebo, having been stratified on the basis of Candida species (Candida albicans vs. non-albicans species of Candida). Inclusion criteria included clinical evidence of active infection at trial entry plus growth of Candida species on culture of a specimen from a clinically significant site within 3 days after initiation of study treatment. The primary efficacy variable was overall response to treatment (clinical and mycological resolution) by day 10.Results. Of the 139 patients enrolled from Europe and the United States, 117 were included in the modified intention-to-treat population. A complete overall response by day 10 was obtained for 29 (48%) of 61 patients in the amphotericin B group, compared with 47 (84%) of 56 patients in the Mycograb combination therapy group (odds ratio [OR], 5.8; 95% confidence interval [CI], 2.41-13.79;). The following efficacy criteria were also met: clinical response (52% vs. 86%; OR, 5.4; 95% CI, 2.21-13.39; P < .001), mycological response (54% vs. 89%; OR, 7.1; 95% CI, 2.64-18.94; P < .001), Candida-attributable mortality (18% vs. 4%; OR, 0.2; 95% CI, 0.04- 0.80; P = .025), and rate of culture-confirmed clearance of the infection (hazard ratio, 2.3; 95% CI, 1.4-3.8; P = .001). Mycograb was well tolerated.Conclusions. Mycograb plus lipid-associated amphotericin B produced significant clinical and culture-confirmed improvement in outcome for patients with invasive candidiasis.