Evaluation of Dexamethasone in the Treatment of Herpes Simplex Virus Encephalitis: An Open-Label, Randomized Controlled Trial with Observer-Blinded Assessment

The primary objective of this study is to evaluate the efficacy of **corticosteroids**, specifically dexamethasone, in improving the neuropsychological prognosis of patients with **Herpes Simplex Virus Encephalitis** over a period of six months. This is clinically relevant as it aims to determine whether the addition of corticosteroids can enhance cognitive recovery and overall neurological outcomes in affected individuals.

Secondary objectives include assessing various outcomes at specified intervals: - Neuropsychological and cognitive outcomes at 30 days/discharge, 6 months, and 18 months. - Clinical outcomes. - Functional outcomes at 30 days/discharge, 6 months, and 18 months. - Biomarker outcomes at baseline, 4 days, 2 weeks, and 6 months. - Safety outcomes at 2 weeks. - Health status and quality of life at 6 months and 18 months.

The clinical trial focuses on individuals diagnosed with **Herpes Simplex Virus Encephalitis**. The study population includes both male and female participants aged 18 years and older. Participants are required to have laboratory-confirmed HSV through a positive PCR on a CSF sample and must be receiving intravenous aciclovir. The trial does not involve a vulnerable population. Participants must be affiliated with social security and have provided written informed consent. The sponsor has not provided information regarding the total number of participants. The selection criteria emphasize acute or subacute alterations in consciousness, cognition, personality, or behavior persisting for more than 24 hours. Lifestyle considerations such as diet and physical activity are not specified in the available data.

The clinical trial is designed to evaluate the efficacy of **dexamethasone** in improving neuropsychological outcomes in patients with **Herpes Simplex Virus Encephalitis**. This study is structured as an open-label, randomized, controlled trial with an observer-blinded evaluation at six months. The trial is expected to run from April 25, 2019, to April 25, 2025. Participants will be randomly assigned to receive either the investigational product or a control treatment, with the primary endpoint being the verbal memory score assessed by the Wechsler Memory Scale (WMS-IV) Auditory Memory Index at six months.

Study visits are sequenced to ensure comprehensive data collection and participant safety. The inclusion visit, or screening, will confirm eligibility based on criteria such as laboratory-confirmed HSV by positive PCR on CSF samples, age of 18 years or older, and written informed consent. Participants will then undergo baseline assessments before randomization. Follow-up visits will occur at specified intervals, including at 30 days or discharge, and at six and 18 months, to evaluate secondary endpoints such as neuropsychological, cognitive, clinical, functional, biomarker, safety, and quality of life outcomes. The end-of-study visit will conclude the participant's involvement, ensuring all necessary data is collected and any remaining health concerns are addressed.

The expected length of participant involvement is up to 18 months, with conditions for early termination including withdrawal of consent, adverse events, or protocol non-compliance. The trial aims to provide valuable insights into the potential benefits of corticosteroids in the treatment of this condition, with a focus on long-term neuropsychological outcomes.

The clinical trial involves the administration of **Dexamethasone**, a corticosteroid, in the form of an **oral solution**. The product, named "Dexamethasone 20mg/5ml Oral Solution," is manufactured by Synchrony Pharma Ltd. The active substance, dexamethasone, is of chemical origin and is classified under the ATC code H02AB02. The pharmaceutical form is an oral solution, and the medication is administered intravenously. The maximum daily dose is 40 mg, with a total maximum dose of 40 mg over a treatment period of up to 4 days. The trial aims to evaluate the efficacy of dexamethasone in improving the neuropsychological outcomes in patients with Herpes Simplex Virus Encephalitis over a 6-month period.

In addition to the experimental treatment, the study may include standard-of-care therapy as a non-experimental treatment. The trial is designed as an open-label, randomized controlled trial with an observer-blinded evaluation at 6 months. Participant compliance with the dosing schedule will be monitored throughout the study to ensure adherence to the treatment protocol. No pediatric formulation is involved in this trial, and the product is not classified as an orphan drug. The trial does not involve any comparator treatment or placebo.

Efficacy in the clinical trial titled "Dexamethasone in Herpes Simplex Virus Encephalitis" will be assessed using a range of primary and secondary endpoints. The primary endpoint is the **Verbal memory score**, evaluated by the Wechsler Memory Scale (WMS-IV) Auditory Memory Index at 6 months, with a single-blind evaluation. Secondary endpoints include various neuropsychological outcome measures assessed at 6 and 18 months, such as visual, immediate, and delayed memory using WMS-IV, processing speed and working memory using WAIS-IV, and higher executive function using Trail Making Tests Part A and B. Additionally, anxiety and depression will be measured using the Beck Depression Inventory (BDI) and Beck Anxiety Inventory (BAI).

Cognitive outcomes will be evaluated at 30 days/discharge, 6 months, and 18 months using the Addenbrooke’s Cognitive Assessment revised (ACE-III). Clinical outcomes will include the incidence of epilepsy, time to hospital discharge, requirement of HDU/ITU admission, time to cessation of ventilator support, time to recovery of Glasgow Coma Scale (GCS), and survival. Functional outcomes will be measured at 30 days/discharge, 6 months, and 18 months using the Modified Rankin Score, Barthel Index, Liverpool Outcome Score, and Glasgow Outcome Score.

Biomarker outcomes will be assessed at baseline, 4 days, 2 weeks, and 6 months, including transcriptomic and proteomic profiling on blood and cerebrospinal fluid (CSF), and anti-NMDA receptor antibody testing. Safety outcomes will be evaluated at 2 weeks, focusing on the proportion of patients with detectable HSV in CSF. Health status and quality of life will be measured at 6 and 18 months using the EuroQOL-5D-5L and SF-36 instruments. These assessments will provide comprehensive data on the efficacy of dexamethasone in improving neuropsychological outcomes in patients with Herpes Simplex Virus Encephalitis.