美国国立卫生研究所H. Clifford Lane研究组对埃博拉病毒疾病疗法进行了一项随机对照试验。该项研究成果发表在2019年11月27日出版的《新英格兰医学杂志》上。

虽然目前已开发出埃博拉病毒病（EVD）的几种实验疗法，但究竟哪种疗法的安全性和有效性最好仍需随机对照试验来进行评估。

刚果民主共和国于2018年8月爆发了EVD，2018年11月20日至2019年8月9日，研究组在刚果进行了4种EVD研究疗法的随机试验。共招募了673例埃博拉病毒RNA阳性的患者，均接受标准治疗，并按1：1：1：1随机分组，其中169名接受三单克隆抗体ZMapp，175名接受抗病毒药物Remdesivir，174名接受单抗MAb114，155名接受三单克隆抗体REGN-EB3治疗。

治疗28天时，MAb114组中有61名（35.1%）患者死亡，ZMapp组中有84名（49.7%），差异不显著；REGN-EB3组中有52名（33.5%）死亡，ZMapp亚组154名患者中有79名（51.3%）死亡，差异显著。入院前症状持续时间较短，病毒载量、血清肌酐和转氨酶水平基线值较低的患者，生存率较高。共发生4起严重不良事件，均认为与试验药物有关。

总之，MAb114和REGN-EB3在降低EVD死亡率方面均优于ZMapp。疾病暴发期间可进行科学伦理合理的临床研究，以帮助应对疫情。

附：英文原文

Title: A Randomized, Controlled Trial of Ebola Virus Disease Therapeutics

Author: Sabue Mulangu, M.D.,, Lori E. Dodd, Ph.D.,, Richard T. Davey, Jr., M.D.,, Olivier Tshiani Mbaya, M.D.,, Michael Proschan, Ph.D.,, Daniel Mukadi, M.D.,, Mariano Lusakibanza Manzo, Ph.D.,, Didier Nzolo, M.D.,, Antoine Tshomba Oloma, M.D.,, Augustin Ibanda, B.S.,, Rosine Ali, M.S.,, Sinaré Coulibaly, M.D.,, Adam C. Levine, M.D.,, Rebecca Grais, Ph.D.,, Janet Diaz, M.D.,, H. Clifford Lane, M.D.,, Jean-Jacques Muyembe-Tamfum, M.D.,, and the PALM Writing Group

Issue&Volume: 2019-11-27

Abstract: 

BACKGROUND
Although several experimental therapeutics for Ebola virus disease (EVD) have been developed, the safety and efficacy of the most promising therapies need to be assessed in the context of a randomized, controlled trial.

METHODS
We conducted a trial of four investigational therapies for EVD in the Democratic Republic of Congo, where an outbreak began in August 2018. Patients of any age who had a positive result for Ebola virus RNA on reverse-transcriptase–polymerase-chain-reaction assay were enrolled. All patients received standard care and were randomly assigned in a 1:1:1:1 ratio to intravenous administration of the triple monoclonal antibody ZMapp (the control group), the antiviral agent remdesivir, the single monoclonal antibody MAb114, or the triple monoclonal antibody REGN-EB3. The REGN-EB3 group was added in a later version of the protocol, so data from these patients were compared with those of patients in the ZMapp group who were enrolled at or after the time the REGN-EB3 group was added (the ZMapp subgroup). The primary end point was death at 28 days.

RESULTS
A total of 681 patients were enrolled from November 20, 2018, to August 9, 2019, at which time the data and safety monitoring board recommended that patients be assigned only to the MAb114 and REGN-EB3 groups for the remainder of the trial; the recommendation was based on the results of an interim analysis that showed superiority of these groups to ZMapp and remdesivir with respect to mortality. At 28 days, death had occurred in 61 of 174 patients (35.1%) in the MAb114 group, as compared with 84 of 169 (49.7%) in the ZMapp group (P=0.007), and in 52 of 155 (33.5%) in the REGN-EB3 group, as compared with 79 of 154 (51.3%) in the ZMapp subgroup (P=0.002). A shorter duration of symptoms before admission and lower baseline values for viral load and for serum creatinine and aminotransferase levels each correlated with improved survival. Four serious adverse events were judged to be potentially related to the trial drugs.

CONCLUSIONS
Both MAb114 and REGN-EB3 were superior to ZMapp in reducing mortality from EVD. Scientifically and ethically sound clinical research can be conducted during disease outbreaks and can help inform the outbreak response. (Funded by the National Institute of Allergy and Infectious Diseases and others; PALM ClinicalTrials.gov number, NCT03719586. opens in new tab.)

DOI: 10.1056/NEJMoa1910993

Source: https://www.nejm.org/doi/full/10.1056/NEJMoa1910993