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NCT Number: NCT05452928

Aciclovir Versus Placebo for HSV-2 Meningitis

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

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Key information

Conditions

Herpes Simplex 2 Central Nervous System Diseases Central Nervous System Infections Central Nervous System Viral Diseases Infections Meningitis Meningitis, Aseptic Meningitis, Viral Nervous System Diseases Neuroinflammatory Diseases Virus Diseases

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 4

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • 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

Exclusion criteria

  • 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

Treatment and study plan

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.

Other names: Valacyclovir

Placebo

Drug

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

Primary outcomes

  1. Primary endpoint (proportion with a Total Morbidity Score)

    Time frame: 7 days since randomisation

    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.

Secondary outcomes

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

    Time frame: 7 days since randomisation

    Proportion of patients with ≤50% reduction of Total Morbidity Score since randomisation. Please see characterization of score under primary endpoint.

  2. Secondary endpoint 2 Extended Glasgow outcome scale score

    Time frame: 7 days, 3 months, and 12 months since randomisation

    Extended Glasgow outcome scale score. Range 1 to 8 with higher scores indicating better outcome.

  3. Secondary endpoint 3 All-cause mortality

    Time frame: 7 days, 3 months, and 12 months since randomisation

    All-cause mortality

  4. Secondary endpoint 4 EQ-5D-5L

    Time frame: 7 days, 3 months, and 12 months since randomisation

    EQ-5D-5L. Comprises 5 questions with an ordinal scale from 1 to 5 with higher scores indicating more morbidity. Finally, a visual analog score is filled ranging from 0 to 100 with higher scores indicating better health.

  5. Secondary endpoint 5 Mental Fatigue Scale

    Time frame: 7 days, 3 months, and 12 months since randomisation

    Mental Fatigue Scale. Comprises 14 questions with scores from 0 to 3 with higher values suggesting more morbidity. A combined score >10.5 usually suggests mental fatigue problems.

  6. Secondary endpoint 6 (SF-36)

    Time frame: 7 days, 3 months, and 12 months since randomisation

    Short Form Health Survey 36 (SF-36). Scores eight different domains from 0 to 100 with higher values indicating no disability.

  7. Secondary outcome 7 neurological deficit

    Time frame: 7 days, 3 months, and 12 months since randomisation

    Any new neurological deficit reported by patient or observed during clinical examination

  8. Secondary outcome 8 Completion of assigned treatment

    Time frame: 7 days since randomisation

    Completion of assigned treatment (active or placebo) assessed by administered intravenous or oral treatment as signed off by nurses in hospitalized patients and pill counts for patients discharged with oral study drug.

  9. Secondary outcome 9 complications

    Time frame: 7 days since randomisation

    Peripheral venous line associated complications (i.e. catheter-associated infection, thrombosis, or haemorrhage).

  10. Secondary outcome 10Severe adverse events

    Time frame: 7 days since randomisation

    Severe adverse events, i.e. incident treatment-emergent serious adverse events.

Study contacts

Contact information is provided by the study sponsor or research team.

Henrik Nielsen, Professor

CONTACT

[email protected]

004597663920

Jacob Bodilsen, MD

CONTACT

[email protected]

004597663920

Sponsors and collaborators

Lead sponsor

Jacob Bodilsen

Other

Registry information

Official study title

Aciclovir for HSV-2 Meningitis: A Double-blind Randomised Controlled Trial (AMEN)

Acronym: AMEN

Important dates

Study start
2026
Primary completion
2028
Study completion
2029
First posted
Jul 12, 2022
Registry last updated
Oct 1, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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