Dexamethasone in Herpes Simplex Virus Encephalitis

Phase 3

• Conditions: HSV Encephalitis
• Interventions: Drug: Dexamethasone

• Registration Number: NCT03084783
• Lead Sponsor: University Hospital, Grenoble

Brief Summary

Encephalitics is a serious condition in which the brain becomes inflamed (swollen). It usually happens as a direct result of virus, such as herpes simplex virus (HSV).

HSV encephalitis is often treated with the drug acyclovir (an antiviral drug which slows the growth and spread of HSV in the body). Despite this however, around 2 out of every 3 people will have memory difficulties long term. Dexamethasone is a corticosteroid medication, which works by preventing the release of natural chemicals in the body which cause inflammation. It is possible that dexamethasone could help to reduce in swelling of the brain may improve the recovery of patients with HSV encephalitis. The aim of this study is to find out whether treatment with dexamethasone can improve long-term health outcomes in adults with HSV Encephalitis.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2017-02-03
• Study First Submitted QC: 2017-03-14
• Study First Posted: 2017-03-21
• Study Start: 2018-11-01
• Status Verified: 2020-09
• Last Update Submitted: 2020-09-03
• Last Update Posted: 2020-09-04
• Primary Completion: 2020-11-01
• Study Completion: 2020-12-01

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Suspected encephalitis criteria: Acute or subacute (up to 4 weeks) alteration in consciousness, cognition, personality or behaviour* persisting for > 24 hours Laboratory confirmed HSV by positive PCR on CSF sample.

• Receiving intravenous aciclovir dosed at 10mg/kg TDS or at a reduced dose in renal impairment
• Age ≥ 18 years
• Person affiliated to social security
• Written informed consent has been given by the patient or their legal representative

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Exclusion Criteria

• Currently receiving oral or injectable corticosteroid therapy; including treatment with oral or injectable corticosteroids in the last 30 days.

• History of hypersensitivity to corticosteroids

• Immunosuppression secondary to:

  • Known HIV infection & CD4 count under 200cell/mm3
  • Biologic therapy or other immunosuppressive agents [azathioprine, methotrexate, ciclosporin]
  • Solid organ transplant on immunosuppression
  • Bone marrow transplant
  • Currently undergoing a course of chemotherapy or radiotherapy
  • Known immunodeficiency syndrome [other than HIV]
  • Known haematological malignancy

• Pre-existing indwelling ventricular devices

• Peptic ulcer disease in the last 6 months: defined as a peptic ulcer seen at previous endoscopy or an upper gastrointestinal bleed causing ≥ 2 unit haemoglobin drop

• Currently on an antiretroviral regime containing rilpivirine

• Patients under legal protection, administrative or judicial control

• Pregnancy / Breast feeding and parturient

• Subject in exclusion period of another study

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Intervention group	Dexamethasone	Participants receive dexamethasone 10mg intravenously 6 hourly for 4 days.

Primary Outcome Measures

Name	Time	Method
Calcul of verbal memory score	at 6 months post randomization	The primary outcome is a verbal memory score as determined by the Wechsler Memory Scale (WMS-IV) Auditory Memory Index, at 6 months post randomisation.

Secondary Outcome Measures

Name	Time	Method
Incidence of epilepsy	during 18 months	clinical outcome
Anti NMDA receptor antibody testing	at 6 months	Biomarker outcome
Visual Memory Index assessed by the Wechsler Memory Scale	6 months and 18 months post randomization	Neuropsychological outcome
Processing Working Memory - assessed by the Wechsler Adult Intelligence Scale version IV	6 months and 18 months post randomization	Neuropsychological outcome
Anxiety -assessed by self-completed Beck Anxiety Inventory	6 months and 18 months post randomization	Neuropsychological outcome
Higher executive function -assessed by Trail Making Test Parts A and B	6 months and 18 months post randomization	Neuropsychological outcome
Depression -assessed by self-completed Beck Depression Inventory Inventory	6 months and 18 months post randomization	Neuropsychological outcome
Cognitive Assessment assessed by Addenbrooke's Cognitive Assessment revised (ACE-III)	at 30 days/discharge, 6 and 18 months
Time to recovery of Glasgow Coma Scale (GCS)	during 18 months	clinical outcome
Transcriptomic and proteomic profiling on CSF	at baseline and 2 weeks	Biomarker outcomes
Proportion of patients with detectable HSV in CSF	at 2 weeks	Safety Outcome
Health Status Measured by the EuroQOL-5D-5L questionnaire	at 6 and 18 months
Quality of Life measured by SF-36 questionnaires	at 6 and 18 months
Measurement of temporal lobe volume (as % of intra-cranial volume)	Baseline, 2 weeks, 6 months and 18 months	Imaging Outcomes
Measurement of Whole brain volume (as % of intra-cranial volume)	Baseline, 2 weeks, 6 months and 18 months	Imaging Outcomes
Transcriptomic and proteomic profiling on blood	at baseline, 4 days, 2 weeks, and 6 months	Biomarker outcome
Requirement of intensive care or high dependency admission	during 18 months	clinical outcome

Trial Locations

Locations (8)

CHRU de Nancy, Hopitaux de Brabois; 🇫🇷 Vandoeuvre Les Nancy, France

CHU Strasbourg; 🇫🇷 Strasbourg, France

Hôpital Charles Nicolle; 🇫🇷 Rouen, France

Hôpital Delafontaine; 🇫🇷 Saint-Denis, France

Hôpital Bichat-Claude Bernard, APHP; 🇫🇷 Paris, France

CHU Hôtel-Dieu; 🇫🇷 Nantes, France

Hôpital Gui de Chauliac; 🇫🇷 Montpellier, France

CHU Rennes, Hôpital Pontchaillou; 🇫🇷 Rennes, France