A Randomized, Controlled Trial of ZMapp for Ebola Virus Infection.
A Randomized, Controlled Trial of ZMapp for Ebola Virus Infection.
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DOI：
10.1056/nejmoa1604330
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发表时间：
2016-10-13
期刊：
影响因子：
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通讯作者：
Malvy D
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作者：
PREVAIL II Writing Group;Multi-National PREVAIL II Study Team;Davey RT Jr;Dodd L;Proschan MA;Neaton J;Neuhaus Nordwall J;Koopmeiners JS;Beigel J;Tierney J;Lane HC;Fauci AS;Massaquoi MBF;Sahr F;Malvy D
来自非人灵长类动物的研究数据表明，三联单克隆抗体鸡尾酒ZMapp是一种有前途的埃博拉病毒病（EVD）免疫治疗方法。从2015年3月开始，我们在西非通过聚合酶链反应（PCR）检测诊断的EVD患者中进行了一项ZMapp+当前标准治疗与当前标准治疗的随机对照试验。任何年龄的合格患者以1：1的比例随机分配接受当前标准治疗或当前标准治疗加三次ZMapp静脉输注（50 mg/kg体重，每三天一次）。根据基线PCR循环阈值（≤22 vs. >22）和入组国家对患者进行分层。口服法匹拉韦是几内亚现行标准治疗的一部分。主要终点是28天时的死亡率。在利比里亚、塞拉利昂、几内亚和美国的研究中心共入组了72例患者。在71名可以评估的患者中，21名死亡，总病死率为30%。仅接受当前标准治疗的35例患者中有13例（37%）死亡，接受当前标准治疗加ZMapp的36例患者中有8例（22%）死亡。观察到ZMapp加当前标准治疗优于单独使用当前标准治疗的后验概率为91.2%，低于预定阈值97.5%。上级。频率主义分析得出了类似的结果（ZMapp的死亡率绝对差异为-15个百分点; 95%置信区间为-36至7）。在所有年龄组中，基线病毒载量是死亡率和住院时间的强预测因素。在这项假定的EVD治疗药物的随机对照试验中，尽管ZMapp的估计效果似乎是有益的，但结果不符合预先规定的疗效统计阈值。（由国家过敏和传染病研究所等资助; PREVAIL II ClinicalTrials.gov编号，NCT 02363322。
Data from studies in nonhuman primates suggest that the triple monoclonal antibody cocktail ZMapp is a promising immune-based treatment for Ebola virus disease (EVD). Beginning in March 2015, we conducted a randomized, controlled trial of ZMapp plus the current standard of care as compared with the current standard of care alone in patients with EVD that was diagnosed in West Africa by polymerase-chain-reaction (PCR) assay. Eligible patients of any age were randomly assigned in a 1:1 ratio to receive either the current standard of care or the current standard of care plus three intravenous infusions of ZMapp (50 mg per kilogram of body weight, administered every third day). Patients were stratified according to baseline PCR cycle-threshold value for the virus (≤22 vs. >22) and country of enrollment. Oral favipiravir was part of the current standard of care in Guinea. The primary end point was mortality at 28 days. A total of 72 patients were enrolled at sites in Liberia, Sierra Leone, Guinea, and the United States. Of the 71 patients who could be evaluated, 21 died, representing an overall case fatality rate of 30%. Death occurred in 13 of 35 patients (37%) who received the current standard of care alone and in 8 of 36 patients (22%) who received the current standard of care plus ZMapp. The observed posterior probability that ZMapp plus the current standard of care was superior to the current standard of care alone was 91.2%, falling short of the prespecified threshold of 97.5%. Frequentist analyses yielded similar results (absolute difference in mortality with ZMapp, −15 percentage points; 95% confidence interval, −36 to 7). Baseline viral load was strongly predictive of both mortality and duration of hospitalization in all age groups. In this randomized, controlled trial of a putative therapeutic agent for EVD, although the estimated effect of ZMapp appeared to be beneficial, the result did not meet the prespecified statistical threshold for efficacy. (Funded by the National Institute of Allergy and Infectious Diseases and others; PREVAIL II ClinicalTrials.gov number, NCT02363322.)