Aciclovir Versus Placebo for HSV-2 Meningitis

Herpes Simplex 2 Clinical Trial

— AMEN  

Official title:

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

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05452928
• Other study ID #: AMEN1
• Secondary ID: 2020-000033-41
• Status: Not yet recruiting
• Phase: Phase 4
• Start date: January 1, 2024
• Est. completion date: June 1, 2028

Study information

• Verified date: January 2023
• Source: Aalborg University Hospital
• Contact: Jacob Bodilsen, MD
• Phone: 004597663920
• Email: jacob.bodilsen[@]rn.dk
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 150
• Est. completion date: June 1, 2028
• Est. primary completion date: June 1, 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: N/A and older

Eligibility

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

Related Conditions & MeSH terms

• Herpes Simplex
• Herpes Simplex 2
• Meningitis

Intervention

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

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
Jacob Bodilsen

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Primary endpoint (proportion with a Total Morbidity Score)	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.	7 days since randomisation
Secondary	Secondary endpoint 1 (Proportion of patients with =50% reduction of Total Morbidity Score)	Proportion of patients with =50% reduction of Total Morbidity Score since randomisation. Please see characterization of score under primary endpoint.	7 days since randomisation
Secondary	Secondary endpoint 2 Extended Glasgow outcome scale score	Extended Glasgow outcome scale score. Range 1 to 8 with higher scores indicating better outcome.	7 days, 3 months, and 12 months since randomisation
Secondary	Secondary endpoint 3 All-cause mortality	All-cause mortality	7 days, 3 months, and 12 months since randomisation
Secondary	Secondary endpoint 4 EQ-5D-5L	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.	7 days, 3 months, and 12 months since randomisation
Secondary	Secondary endpoint 5 Mental Fatigue Scale	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.	7 days, 3 months, and 12 months since randomisation
Secondary	Secondary endpoint 6 (SF-36)	Short Form Health Survey 36 (SF-36). Scores eight different domains from 0 to 100 with higher values indicating no disability.	7 days, 3 months, and 12 months since randomisation
Secondary	Secondary outcome 7 neurological deficit	Any new neurological deficit reported by patient or observed during clinical examination	7 days, 3 months, and 12 months since randomisation
Secondary	Secondary outcome 8 Completion of assigned treatment	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.	7 days since randomisation
Secondary	Secondary outcome 9 complications	Peripheral venous line associated complications (i.e. catheter-associated infection, thrombosis, or haemorrhage).	7 days since randomisation
Secondary	Secondary outcome 10Severe adverse events	Severe adverse events, i.e. incident treatment-emergent serious adverse events.	7 days since randomisation