Herpes Simplex 2Phase 4AMENNCT05452928
Aciclovir Versus Placebo for HSV-2 Meningitis
A Phase 4 study testing Acyclovir 50 MG/ML in people with Herpes Simplex 2 and Meningitis, Viral, run by Jacob Bodilsen.
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 Read more about this study
- Who is it for?
- Any ageHealthy volunteers can take part
- Conditions the study is for
- Herpes Simplex 2, Meningitis, Viral
- What is being tested?
- Acyclovir 50 MG/ML
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 150 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2027to 31 Dec 2032
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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)
Show all 12Show fewer
- 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
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Aciclovir for HSV-2 Meningitis: A Double-blind Randomised Controlled Trial (AMEN)
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
- Conditions
- Herpes Simplex 2, Meningitis, Viral
- Being tested
- Acyclovir 50 MG/ML, Placebo
- Keywords
- meningitis, HSV-2, Herpes simplex 2, viral meningitis, aseptic meningitis, acyclovir, valacyclovir, aciclovir, valaciclovir
- Medical subject headings
- Meningitis, Viral, Meningitis, Meningitis, Aseptic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Acyclovir 50 MG/MLDrug
Also called Valacyclovir
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.
PlaceboDrug
Placebo either in IV formulation or as tablets identical to valacyclovir tablets.
| Study group | Role | What they receive |
|---|---|---|
| Active arm | Active comparator | 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). Receives: Drug: Acyclovir 50 MG/ML |
| Placebo | Placebo comparator | Randomisation to 7 days of IV and/or oral placebo. Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 7 days since randomisation
Secondary outcomes (10)
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.
Measured: 7 days since randomisation
Secondary endpoint 2 Extended Glasgow outcome scale score
Extended Glasgow outcome scale score. Range 1 to 8 with higher scores indicating better outcome.
Measured: 7 days, 3 months, and 12 months since randomisation
Secondary endpoint 3 All-cause mortality
All-cause mortality
Measured: 7 days, 3 months, and 12 months since randomisation
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.
Measured: 7 days, 3 months, and 12 months since randomisation
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.
Measured: 7 days, 3 months, and 12 months since randomisation
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.
Measured: 7 days, 3 months, and 12 months since randomisation
Secondary outcome 7 neurological deficit
Any new neurological deficit reported by patient or observed during clinical examination
Measured: 7 days, 3 months, and 12 months since randomisation
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.
Measured: 7 days since randomisation
Secondary outcome 9 complications
Peripheral venous line associated complications (i.e. catheter-associated infection, thrombosis, or haemorrhage).
Measured: 7 days since randomisation
Secondary outcome 10Severe adverse events
Severe adverse events, i.e. incident treatment-emergent serious adverse events.
Measured: 7 days since randomisation
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jul 2022
- Study start1 Jan 2027 (estimated)
- Primary completion31 Dec 2031 (estimated)
- Study completion31 Dec 2032 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Herpes Simplex 2Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Investigator initiated, double-blind, 2-arm (1:1 allocation), international, multicentre, parallel group, randomised, placebo controlled, superiority trial.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Jacob Bodilsen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Jacob Bodilsen, Aalborg University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05452928
- Sponsor's protocol ID
- AMEN1
- Other IDs
- 2020-000033-41
- Acronym
- AMEN
- Status last verified
- Oct 2026
- First submitted
- 1 Jul 2022
- Last updated
- 28 Oct 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data will be deposited at Mendeley Data (https://data.mendeley.com/).
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Aciclovir for HSV-2 Meningitis: A Double-blind Randomised Controlled Trial (AMEN)
- ClinicalTrials.gov ID
- NCT05452928
- Acronym / sponsor ID
- AMEN / AMEN1
- Conditions
- Herpes Simplex 2, Meningitis, Viral
- Keywords
- meningitis, HSV-2, Herpes simplex 2, viral meningitis, aseptic meningitis, acyclovir, valacyclovir, aciclovir
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Jacob BodilsenUniversity, hospital or other
- Study start
- 1 Jan 2027 (estimated)
- Primary completion
- 31 Dec 2031 (estimated)
- Study completion
- 31 Dec 2032 (estimated)
- First posted
- 12 Jul 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- Investigator initiated, double-blind, 2-arm (1:1 allocation), international, multicentre, parallel group, randomised, placebo controlled, superiority trial.
| Arm | Type | Receives |
|---|---|---|
| Active arm | Active comparator | Drug: Acyclovir 50 MG/MLRandomisation 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). |
| Placebo | Placebo comparator | Drug: PlaceboRandomisation to 7 days of IV and/or oral placebo. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (6 listed)
- Adults ≥18 years of age admitted on suspicion of viral meningitis defined as:
Key exclusion criteria (12 listed)
- Patients fulfilling any of the following criteria will be excluded:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Acyclovir 50 MG/MLAlso: ValacyclovirPatients 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 | Active arm |
| PlaceboPlacebo either in IV formulation or as tablets identical to valacyclovir tablets. | Drug | Placebo |
Primary outcome
Primary endpoint (proportion with a Total Morbidity Score)
Time frame: 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.
10 secondary outcomes
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2026.
- Individual participant dataSharing planned: Yes. Data will be deposited at Mendeley Data (https://data.mendeley.com/).
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Acyclovir 50 MG/ML in people with Herpes Simplex 2 and Meningitis, Viral, run by Jacob Bodilsen.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 28 Oct 2026. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jacob Bodilsen, MD (004597663920, jacob.bodilsen@rn.dk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Primary endpoint (proportion with a Total Morbidity Score) (time frame: 7 days since randomisation). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 28 Oct 2026.