Aciclovir Versus Placebo for HSV-2 Meningitis

Official title

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

Overview

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

Interventions

• Drug Acyclovir 50 MG/ML
  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.
• Drug Placebo
  Placebo either in IV formulation or as tablets identical to valacyclovir tablets.

Primary outcome measures

• Primary endpoint (proportion with a Total Morbidity Score) [Time frame: 7 days since randomisation]

Secondary outcome measures (10)

• Secondary endpoint 1 (Proportion of patients with ≤50% reduction of Total Morbidity Score) [Time frame: 7 days since randomisation]
• Secondary endpoint 2 Extended Glasgow outcome scale score [Time frame: 7 days, 3 months, and 12 months since randomisation]
• Secondary endpoint 3 All-cause mortality [Time frame: 7 days, 3 months, and 12 months since randomisation]
• Secondary endpoint 4 EQ-5D-5L [Time frame: 7 days, 3 months, and 12 months since randomisation]
• Secondary endpoint 5 Mental Fatigue Scale [Time frame: 7 days, 3 months, and 12 months since randomisation]
• Secondary endpoint 6 (SF-36) [Time frame: 7 days, 3 months, and 12 months since randomisation]
• Secondary outcome 7 neurological deficit [Time frame: 7 days, 3 months, and 12 months since randomisation]
• Secondary outcome 8 Completion of assigned treatment [Time frame: 7 days since randomisation]
• Secondary outcome 9 complications [Time frame: 7 days since randomisation]
• Secondary outcome 10Severe adverse events [Time frame: 7 days since randomisation]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: Yes

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Center list to be confirmed — check the primary protocol.

Identifiers

NCT: NCT05452928 · AMEN1 · 2020-000033-41

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗