TY - JOUR
T1 - Protocol for DexEnceph: A randomised controlled trial of dexamethasone therapy in adults with herpes simplex virus encephalitis
AU - Whitfield, Thomas
AU - Fernandez, Cristina
AU - Davies, Kelly
AU - Defres, Sylviane
AU - Griffiths, Michael
AU - Hooper, Cory
AU - Tangney, Rebecca
AU - Burnside, Girvan
AU - Rosala- Hallas, Anna
AU - Moore, Perry
AU - Das, Kumar
AU - Zuckerman, Mark
AU - Parkes, Laura
AU - Keller, Simon
AU - Roberts, Neil
AU - Easton, Ava
AU - Touati, Saber
AU - Kneen, Rachel
AU - Stahl, J. P.
AU - Solomon, Tom
PY - 2021/7/22
Y1 - 2021/7/22
N2 - Introduction 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. Method 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. Discussion 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. Ethics and dissemination 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. Trial registration numbers ISRCTN11774734, EUDRACT 2015-001609-16.
AB - Introduction 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. Method 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. Discussion 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. Ethics and dissemination 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. Trial registration numbers ISRCTN11774734, EUDRACT 2015-001609-16.
KW - neurological injury
KW - neurology
KW - virology
UR - https://www.mendeley.com/catalogue/88b3cf2f-24ca-3b44-a3d8-1fb414b4e6ab/
U2 - 10.1136/bmjopen-2020-041808
DO - 10.1136/bmjopen-2020-041808
M3 - Article
C2 - 34301646
SN - 2044-6055
VL - 11
JO - BMJ Open
JF - BMJ Open
IS - 7
M1 - e041808
ER -