| Title: |
Safety and efficacy of adjunct dexamethasone in adults with herpes simplex virus encephalitis in the UK (DexEnceph): a multicentre, observer-blind, randomised, phase 3, controlled trial |
| Authors: |
Solomon, Tom; Hooper, Cory; Easton, Ava; Rosala-Hallas, Anna; Facer, Bethany; Moore, Perry; Keller, Simon S.; Whitfield, Thomas; Fernandez, Cristina; Kneen, Rachel; Griffiths, Michael J.; Das, Kumar; Moore, Shona C.; Davies, Kelly; Wheatley, Dianne; Stahl, Jean Paul; Hardwick, Ben; Defres, Sylviane; Michael, Benedict D.; Handel, Adam; Winterburn, Alison; Fower, Andrew; Misbahuddin, Anjum; Sharrack, Basil; Mclean, Brendan; Davies, Brendan; Gran, Bruno; Subudhi, Chinari Pradeep Kumar; Kosmidis, Chris; Jackson, Clare; Leen, Clifford; Graham, Clive; Dunai, Cordelia; Lashley, Daniel; McLauglan, Danielle; van de Beek, Diederik; Gkrania-Klotsas, Effrossyni; James, Elizabeth; Hodel, Eva Maria; Ashoor, Farhiya; McGill, Fiona; MacKay, Graham; Emsley, Hedley; Allroggen, Holger; Coebergh, Jan; Flatley, Janet; Cochius, Jeffrey; Chataway, Jeremy; Abraham, Jijee Annie; Dalton, Joanne; Day, John; Cleaver, Jonathan; Ajdukiewicz, Katherine; Jeffery, Katie; Abdel-Aziz, Khaled; Parkes, Laura; Le Maréchal, Marion; Zuckerman, Mark; Roberts, Mark; Whyte, Martin; Wiselka, Martin; Jones, Matthew; Perry, Meghan; Marta, Monica; Syed, Nazar Ulla; Roberts, Neil; Davies, Nick; Egbe, Franklyn N.; Leach, Oliver; Reiboeck, Pablo Garcia; Collini, Paul; Karadi, Rangaprasad; Tangey, Rebecca; McEwen, Ruth; Jacob, Saiju; Irani, Sarosh; Slaght, Sean J.; Sheilds, Simon; Ellis, Simon; Chakraborty, Tapas; Harrower, Timothy P.; Corrah, Tumena; Schwab, Ulrich; Burnside, Girvan; Ellul, Mark A. |
| Publisher Information: |
Elsevier |
| Publication Year: |
2026 |
| Collection: |
University of Nottingham: Repository@Nottingham |
| Description: |
BackgroundHerpes simplex virus (HSV) encephalitis is characterised by inflammation and swelling of the brain, resulting in death or severe neurocognitive sequelae. HSV encephalitis is treated with the antiviral aciclovir but still has substantial mortality and morbidity. Adjunct corticosteroids are sometimes used, but whether they improve the outcome is unclear. We aimed to establish the safety and efficacy of adjunct corticosteroids in HSV encephalitis.MethodsIn this multicentre, observer-blind, randomised, phase 3 trial, adults with HSV encephalitis admitted to 53 hospitals in the UK were randomly assigned to receive intravenous dexamethasone (10 mg, four times daily for 4 days) plus intravenous aciclovir (10 mg/kg three times daily for at least 14 days; dexamethasone group), or intravenous aciclovir alone (control group). Eligible patients aged 16 years or older had suspected encephalitis (a febrile illness with new onset seizure, new focal neurological signs or alteration in consciousness, cognition, personality, or behaviour), with positive HSV type 1 or type 2 PCR test in CSF. Participants were randomly assigned by the trial team at the recruiting site, using a secure web-based randomisation programme. The primary outcome was verbal memory score at 26 weeks, measured by the Wechsler Memory Scale (WMS)-IV auditory memory index. Analyses of primary and secondary outcomes were performed according to the modified intention-to-treat principle, and safety analyses were based on whether participants received at least one dose of the study drug. Trial neuropsychologists assessing the primary outcome, and statisticians involved in the study's primary outcome, were masked to treatment group allocation. The trial is registered with the International Standard Randomised Controlled Trial Number Registry, ISRCTN11774734, and EudraCT, EudraCT2016-004835-19, and is completed.FindingsBetween Sept 22, 2016, and Feb 2, 2022, 94 patients with HSV encephalitis were recruited, 47 (20 [43%] female and 27 [57%] male) to the ... |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| Relation: |
https://nottingham-repository.worktribe.com/output/59710817; Lancet Neurology; Volume 25; Issue 2; Pagination 136-146 |
| DOI: |
10.1016/S1474-4422%2825%2900454-5 |
| DOI: |
10.1016/S1474-4422(25)00454-5 |
| Availability: |
https://doi.org/10.1016/S1474-4422%2825%2900454-5; https://nottingham-repository.worktribe.com/file/59710817/1/Safety%20and%20efficacy%20of%20adjunct%20dexamethasone%20in%20adults%20with%20herpes%20simplex%20virus%20encephalitis%20in%20the%20UK%20%28DexEnceph%29%3A%20a%20multicentre,%20observer-blind,%20randomised,%20phase%203,%20controlled%20trial; https://nottingham-repository.worktribe.com/output/59710817; https://doi.org/10.1016/S1474-4422(25)00454-5 |
| Rights: |
openAccess ; https://creativecommons.org/licenses/by/4.0/ |
| Accession Number: |
edsbas.73B0D5AC |
| Database: |
BASE |