Aciclovir Versus Placebo for HSV-2 Meningitis

Phase 4

Not yet recruiting

• Conditions: Herpes Simplex 2; Meningitis, Viral
• Interventions: Drug: Placebo; Drug: Acyclovir 50 MG/ML

• Registration Number: NCT05452928
• Lead Sponsor: Jacob Bodilsen

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

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2022-07-01
• Study First Submitted QC: 2022-07-11
• Study First Posted: 2022-07-12
• Status Verified: 2024-06
• Last Update Submitted: 2024-06-21
• Last Update Posted: 2024-06-24
• Study Start: 2025-06-01
• Primary Completion: 2028-06-01
• Study Completion: 2029-06-01

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 150

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Placebo	Placebo	Randomisation to 7 days of IV and/or oral placebo.
Active arm	Acyclovir 50 MG/ML	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).

Primary Outcome Measures

Name	Time	Method
Primary endpoint (proportion with a Total Morbidity Score)	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 Outcome Measures

Name	Time	Method
Secondary endpoint 1 (Proportion of patients with ≤50% reduction of Total Morbidity Score)	7 days since randomisation	Proportion of patients with ≤50% reduction of Total Morbidity Score since randomisation. Please see characterization of score under primary endpoint.
Secondary endpoint 2 Extended Glasgow outcome scale score	7 days, 3 months, and 12 months since randomisation	Extended Glasgow outcome scale score. Range 1 to 8 with higher scores indicating better outcome.
Secondary endpoint 3 All-cause mortality	7 days, 3 months, and 12 months since randomisation	All-cause mortality
Secondary endpoint 4 EQ-5D-5L	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.
Secondary endpoint 5 Mental Fatigue Scale	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.
Secondary endpoint 6 (SF-36)	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.
Secondary outcome 7 neurological deficit	7 days, 3 months, and 12 months since randomisation	Any new neurological deficit reported by patient or observed during clinical examination
Secondary outcome 8 Completion of assigned treatment	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.
Secondary outcome 9 complications	7 days since randomisation	Peripheral venous line associated complications (i.e. catheter-associated infection, thrombosis, or haemorrhage).
Secondary outcome 10Severe adverse events	7 days since randomisation	Severe adverse events, i.e. incident treatment-emergent serious adverse events.