Dexamethasone in Herpes Simplex Virus Encephalitis Open label Randomized Controlled Trial with an Observer-blinded evaluation at 6 months

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Centre Hospitalier Universitaire Grenoble Alpes

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02]

Trial duration

25 Apr 2019 → 7 May 2025

Decision date (initial)

2024-09-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515985-16-00

EudraCT number

2016-004835-19

ClinicalTrials.gov

NCT03084783

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Others

Estimate the interest of corticoids for the improvement of the neuropsychological forecast in 6 months

Secondary objectives 6

1. Neuropsychological and Cognitive outcome measures [at 30 days/discharge, 6 and 18 months]
2. Clinical Outcome
3. Functional Outcomes [at 30 days/discharge, 6 months and 18 months]
4. Biomarker outcomes [Baseline, 4 days, 2 weeks, 6 months months]
5. Safety Outcomes [2 weeks]
6. Health Status and Quality of Life [6 months and 18 months]

Conditions and MedDRA coding

Herpes Simplex Virus Encephalitis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 6

1. Suspected encephalitis criteria: Acute or subacute (up to 4 weeks) alteration in consciousness, cognition, personality or behaviour* persisting for > 24 hours
2. Laboratory confirmed HSV by positive PCR on CSF sample
3. Receiving intravenous aciclovir dosed at 10mg/kg TDS or at a reduced dose in renal impairment
4. Age ≥ 18 years
5. Person affiliated to social security
6. Written informed consent has been given by the patient or their legal representative

Exclusion criteria 11

1. Currently receiving oral or injectable corticosteroid therapy; including treatment with oral or injectable corticosteroids in the last 30 days
2. History of hypersensitivity to corticosteroids
3. 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
4. Pre-existing indwelling ventricular devices
5. 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
6. Currently on an antiretroviral regime containing rilpivirine
7. Subject under administrative or judicial control, person who are protected under the act
8. Pregnant women, breastfeeding and parturient
9. Active tuberculosis
10. Any other infectious pathology in acute phase
11. Subject in exclusion period of another study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Verbal memory score, as determined by the Wechsler Memory Scale (WMS-IV) Auditory Memory Index at 6 months, single blind evaluation

Secondary endpoints 7

1. Neuropsychological outcome measures [6 months and 18 months]: - Visual, immediate and delayed memory (WMS-IV), Processing speed and working memory(WAIS-IV), & Higher executive function (Trail Making Tests Past A and B) - Anxiety and Depression (BDI & BAI)
2. Cognitive Outcome Measures [at 30 days/discharge, 6 and 18 months] : - Addenbrooke’s Cognitive Assessment revised (ACE-III)
3. Clinical Outcome: - Incidence of epilepsy - Time to hospital discharge - Requirement of HDU/ITU admission - Time to cessation of ventilator support [if any] - Time to recovery of GCS - Survival
4. Functional Outcomes [at 30 days/discharge, 6 months and 18 months] : - Modified Rankin Score, Barthel Index, Liverpool Outcome Score and Glasgow Outcome Score
5. Biomarker outcomes [Baseline, 4 days, 2 weeks, 6 months months]: - Transcriptomic and proteomic profiling on blood at baseline, 4 days, 2 weeks and 6 months & CSF at baseline and 2 weeks - Anti NMDA receptor antibody testing at 4 days (and 2 weeks and 6 months if necessary)
6. Safety Outcomes [2 weeks]: - Proportion of patients with detectable HSV in CSF
7. Health Status and Quality of Life [at 6 and 18 months] :- Measured by the EuroQOL-5D-5L and SF-36

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Centre Hospitalier Universitaire Grenoble Alpes

Sponsor organisation

Centre Hospitalier Universitaire Grenoble Alpes

Address

Boulevard De La Chantourne, Cs 10217, La Tronche Cs 10217 La Tronche

City

Grenoble Cedex 9

Postcode

38043

Country

France

Scientific contact point

Organisation

Centre Hospitalier Universitaire Grenoble Alpes

Contact name

Marion LE MARECHAL

Public contact point

Organisation

Centre Hospitalier Universitaire Grenoble Alpes

Contact name

Marion LE MARECHAL

Locations

1 EU/EEA country · 13 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 11 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

1 submissions — initial application plus substantial / non-substantial modifications