Clinical trial NCT05452928: Aciclovir Versus Placebo for HSV-2 Meningitis
Official title: Aciclovir for HSV-2 Meningitis: A Double-blind Randomised Controlled Trial (AMEN)
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE4
Conditions: Herpes Simplex 2
Meningitis, Viral
Keywords: meningitis
HSV-2
Herpes simplex 2
viral meningitis
aseptic meningitis
acyclovir
valacyclovir
aciclovir
valaciclovir
Lead sponsor: Aalborg University Hospital
Sponsor class: OTHER
First posted: 2022-07-12
Enrollment: 150
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Investigator initiated, double-blind, 2-arm (1:1 allocation), international, multicentre, parallel group, randomised, placebo controlled, superiority trial.
Primary purpose: TREATMENT

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


Eligibility criteria: 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

Primary outcomes:
measure: Primary endpoint (proportion with a Total Morbidity Score)
timeFrame: 7 days since randomisation
Secondary outcomes:
measure: Secondary endpoint 1 (Proportion of patients with ≤50% reduction of Total Morbidity Score)
timeFrame: 7 days since randomisation
measure: Secondary endpoint 2 Extended Glasgow outcome scale score
timeFrame: 7 days, 3 months, and 12 months since randomisation
measure: Secondary endpoint 3 All-cause mortality
timeFrame: 7 days, 3 months, and 12 months since randomisation
measure: Secondary endpoint 4 EQ-5D-5L
timeFrame: 7 days, 3 months, and 12 months since randomisation
measure: Secondary endpoint 5 Mental Fatigue Scale
timeFrame: 7 days, 3 months, and 12 months since randomisation
measure: Secondary endpoint 6 (SF-36)
timeFrame: 7 days, 3 months, and 12 months since randomisation
measure: Secondary outcome 7 neurological deficit
timeFrame: 7 days, 3 months, and 12 months since randomisation
measure: Secondary outcome 8 Completion of assigned treatment
timeFrame: 7 days since randomisation
measure: Secondary outcome 9 complications
timeFrame: 7 days since randomisation
measure: Secondary outcome 10Severe adverse events
timeFrame: 7 days since randomisation
Other outcomes:
Locations:
Study officials:
References: