Aciclovir Versus Placebo for HSV-2 Meningitis

NCT05452928 | Not Yet Recruiting Phase 4 DMC

• 2 other identifiers: AMEN12020-000033-41
• Study Type: interventional
• Target: 150
• Locations: 0 countries
• Sites: N/A

Brief Summary

To determine whether active treatment with (val)acyclovir is superior for treatment of viral meningitis compared with placebo assessed by numbers meeting a primary, objective endpoint at 7 days after randomisation

Conditions

Herpes Simplex 2; Meningitis, Viral

Keywords

meningitis; HSV-2; Herpes simplex 2; viral meningitis; aseptic meningitis; acyclovir; valacyclovir; aciclovir; valaciclovir

Outcome Measures

Primary Outcomes (1)

• Primary endpoint (proportion with a Total Morbidity Score)

  The proportion with a Total Morbidity Score (TMS) \>6 is considered treatment failure. The score is a sum of scores for headache (range 0 to 6), nuchal rigidity (range 0 to 4), photophobia (range 0 to 4), myalgia (range 0 to 4), fever (range 0 to 4), nausea (range 0 to 4). The score thus ranges from 0 to 21 with higher scores indicating more severe symptoms.

  7 days since randomisation

Secondary Outcomes (10)

• Secondary endpoint 1 (Proportion of patients with ≤50% reduction of Total Morbidity Score)

  7 days since randomisation

• Secondary endpoint 2 Extended Glasgow outcome scale score

  7 days, 3 months, and 12 months since randomisation

• Secondary endpoint 3 All-cause mortality

  7 days, 3 months, and 12 months since randomisation

• Secondary endpoint 4 EQ-5D-5L

  7 days, 3 months, and 12 months since randomisation

• Secondary endpoint 5 Mental Fatigue Scale

  7 days, 3 months, and 12 months since randomisation

Study Arms (2)

Active arm

ACTIVE COMPARATOR

Randomisation to 7 days of active treatment with IV aciclovir 10 mg/kg q8h and possibility for oral step-down therapy with valaciclovir 1g q8h, or placebo (IV q8h and/or oral q8h).

Drug: Acyclovir 50 MG/ML

Placebo

PLACEBO COMPARATOR

Randomisation to 7 days of IV and/or oral placebo.

Drug: Placebo

Interventions

Acyclovir 50 MG/ML DRUG

Patients are randomised to active treatment with IV acyclovir with the possibility of step-down to valacyclovir. If the treating physician prefers, initial IV treatment can be omitted and the patient can be treated with valacyclovir throughout the study period.

Also known as: Valacyclovir

Active arm

Placebo DRUG

Placebo either in IV formulation or as tablets identical to valacyclovir tablets.

Placebo

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults ≥18 years of age admitted on suspicion of viral meningitis defined as:
• A clinical presentation consistent with viral meningitis (e.g. headache, nuchal rigidity, photophobia, or fever) AND
• Cerebrospinal fluid (CSF) pleocytosis (\>4 leukocytes x 106/L) AND
• HSV-2 positive by PCR of the CSF
• Glasgow Coma Scale score of 15 AND
• Ability to absorb oral medications

You may not qualify if:

• Patients fulfilling any of the following criteria will be excluded:
• Encephalitis as defined by the International Encephalitis Consortium if diagnosed during standard care (see Glossary)20
• Transverse myelitis as defined by the Transverse Myelitis Consortium Working Group if diagnosed during standard care (see Glossary)21
• Severe immuno-compromise defined as an ongoing need for biological- or chemotherapy (e.g. natalizumab), prednisolone \>20 mg/day for ≥14 days, uncontrolled HIV/AIDS (see glossary), haematological malignancies, and organ transplant recipients14,18,22
• Moderate to severe concomitant genital herpes requiring systemic aciclovir
• Pregnancy (proven by positive urine or plasma human chorionic gonadotropin test in fertile women)
• Hepatic impairment (aspartate aminotransferase or alanine aminotransferase levels \>5 times the upper limit of normal)
• Impaired renal function (estimated glomerular filtration rate \<25 mL/min)
• Intolerance to (val)aciclovir
• Probenecid treatment
• Systemic antiviral therapy with an antiherpetic effect for \>24 hours
• Previous enrolment into this trial

Sponsors & Collaborators

• Jacob Bodilsen: lead

MeSH Terms

Conditions

Meningitis, Viral; Meningitis; Meningitis, Aseptic

Interventions

Acyclovir; Valacyclovir

Condition Hierarchy (Ancestors)

Central Nervous System Viral Diseases; Central Nervous System Infections; Infections; Virus Diseases; Central Nervous System Diseases; Nervous System Diseases; Neuroinflammatory Diseases

Intervention Hierarchy (Ancestors)

Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Central Study Contacts

Jacob Bodilsen, MD

CONTACT

004597663920; jacob.bodilsen@rn.dk

Henrik Nielsen, Professor

CONTACT

004597663920; henrik.nielsen@rn.dk

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: We will use a centralised internet-based computer-generated randomisation schedule prepared and overseen by an experienced statistician. Patients will be randomised in a 1:1 ratio in permuted blocks of two to six and stratified by country, sex, and adjunctive dexamethasone treatment (yes/no).
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-investigator

Model Details: Investigator initiated, double-blind, 2-arm (1:1 allocation), international, multicentre, parallel group, randomised, placebo controlled, superiority trial.

Study Record Dates

• First Submitted: July 1, 2022
• First Posted: July 12, 2022
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): June 1, 2028
• Study Completion (Estimated): June 1, 2029
• Last Updated: October 1, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: Beginning six months and ending three years after publication, an anonymized dataset can be shared.
• Access Criteria: Qualified researchers who provide a methodologically sound proposal.