Department of Clinical Infection, Medical Microbiology and Immunology, University of Liverpool, Liverpool, UK.
Clinical Trials Research Centre, University of Liverpool, Liverpool, UK.
BMJ Open. 2021 Jul 22;11(7):e041808. doi: 10.1136/bmjopen-2020-041808.
Herpes simplex virus (HSV) encephalitis is a rare severe form of brain inflammation that commonly leaves survivors and their families with devastating long-term consequences. The virus particularly targets the temporal lobe of the brain causing debilitating problems in memory, especially verbal memory. It is postulated that immunomodulation with the corticosteroid, dexamethasone, could improve outcomes by reducing brain swelling. However, there are concerns (so far not observed) that such immunosuppression might facilitate increased viral replication with resultant worsening of disease. A previous trail closed early because of slow recruitment.
DexEnceph is a pragmatic multicentre, randomised, controlled, open-label, observer-blind trial to determine whether adults with HSV encephalitis who receive dexamethasone alongside standard antiviral treatment with aciclovir for have improved clinical outcomes compared with those who receive standard treatment alone. Overall, 90 patients with HSV encephalitis are being recruited from a target of 45 recruiting sites; patients are randomised 1:1 to the dexamethasone or control arms of the study. The primary outcome measured is verbal memory as assessed by the Weschler Memory Scale fourth edition Auditory Memory Index at 26 weeks after randomisation. Secondary outcomes are measured up to 72 weeks include additional neuropsychological, clinical and functional outcomes as well as comparison of neuroimaging findings. Patient safety monitoring occurs throughout and includes the detection of HSV DNA in cerebrospinal fluid 2 weeks after randomisation, which is indicative of ongoing viral replication. Innovative methods are being used to ensure recrutiment targets are met for this rare disease.
DexEnceph aims to be the first completed randomised controlled trial of corticosteroid therapy in HSV encephalitis. The results will provide evidence for future practice in managing adults with the condition and has the potential to improve outcomes .
The trial has ethical approval from the UK National Research Ethics Committee (Liverpool Central, REF: 15/NW/0545, 10 August 2015). Protocol V.2.1, July 2019. The results will be published and presented as soon as possible on completion.
ISRCTN11774734, EUDRACT 2015-001609-16.
单纯疱疹病毒（HSV）脑炎是一种罕见的严重脑部炎症形式，常使幸存者及其家人留下毁灭性的长期后果。该病毒特别针对大脑的颞叶，导致记忆（尤其是语言记忆）方面的衰弱问题。有人推测，使用皮质类固醇地塞米松进行免疫调节可以通过减轻脑肿胀来改善结果。但是，有人担心（到目前为止还没有观察到）这种免疫抑制可能会促进病毒复制增加，从而导致疾病恶化。由于招募缓慢，先前的试验提前关闭。
DexEnceph 是一项实用的多中心、随机、对照、开放性、观察者盲法试验，旨在确定接受阿昔洛韦标准抗病毒治疗联合地塞米松治疗的单纯疱疹病毒脑炎成人与接受单纯标准治疗相比，是否具有更好的临床结局。总体而言，正在从 45 个目标招募地点招募 90 名单纯疱疹病毒脑炎患者；患者以 1:1 的比例随机分配到地塞米松或研究的对照组。主要结局测量是随机分组后 26 周时通过 Weschler 记忆量表第四版听觉记忆指数评估的语言记忆。次要结局在 72 周内测量，包括额外的神经心理学、临床和功能结局以及神经影像学发现的比较。在整个过程中进行患者安全性监测，包括随机分组后 2 周时脑脊液中单纯疱疹病毒 DNA 的检测，这表明存在持续的病毒复制。正在使用创新方法来确保这种罕见疾病的招募目标得以实现。
DexEnceph 旨在成为首个单纯疱疹病毒脑炎皮质类固醇治疗的完成随机对照试验。结果将为未来管理成人单纯疱疹病毒脑炎的实践提供证据，并有可能改善结局。
该试验已获得英国国家伦理委员会（利物浦中央，REF：15/NW/0545，2015 年 8 月 10 日）的伦理批准。方案 V.2.1，2019 年 7 月。一旦完成，将尽快公布和发表结果。
ISRCTN85323339，EUDRACT 2015-001609-16。
