Aciclovir Versus Placebo for HSV-2 Meningitis (AMEN)

Jacob Bodilsen

Status and phase: Not yet enrolling; Phase 4

Conditions: Meningitis, Viral; Herpes Simplex 2

Treatments: Drug: Placebo; Drug: Acyclovir 50 MG/ML

Study type: Interventional

Funder types: Other

Identifiers

NCT05452928

2020-000033-41 (EudraCT Number)

AMEN1

Details and patient eligibility

About

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

Enrollment: 150 estimated patients

Sex: All

Volunteers: Accepts Healthy Volunteers

Inclusion criteria

• Adults ≥18 years of age admitted on suspicion of viral meningitis defined as:

  1. A clinical presentation consistent with viral meningitis (e.g. headache, nuchal rigidity, photophobia, or fever) AND
  2. Cerebrospinal fluid (CSF) pleocytosis (>4 leukocytes x 106/L) AND
  3. HSV-2 positive by PCR of the CSF
  4. Glasgow Coma Scale score of 15 AND
  5. Ability to absorb oral medications

Exclusion criteria

• Patients fulfilling any of the following criteria will be excluded:

  1. Encephalitis as defined by the International Encephalitis Consortium if diagnosed during standard care (see Glossary)20
  2. Transverse myelitis as defined by the Transverse Myelitis Consortium Working Group if diagnosed during standard care (see Glossary)21
  3. 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
  4. Moderate to severe concomitant genital herpes requiring systemic aciclovir
  5. Pregnancy (proven by positive urine or plasma human chorionic gonadotropin test in fertile women)
  6. Hepatic impairment (aspartate aminotransferase or alanine aminotransferase levels >5 times the upper limit of normal)
  7. Impaired renal function (estimated glomerular filtration rate <25 mL/min)
  8. Intolerance to (val)aciclovir
  9. Probenecid treatment
  10. Systemic antiviral therapy with an antiherpetic effect for >24 hours
  11. Previous enrolment into this trial

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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150 participants in 2 patient groups, including a placebo group

Active arm

Active Comparator group

Description:

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).

Treatment:

Drug: Acyclovir 50 MG/ML

Placebo

Placebo Comparator group

Description:

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

Treatment:

Drug: Placebo