Aciclovir for HSV-2 Meningitis: A Double-blind Randomised Controlled Trial (AMEN)
试验速览
- 阶段
- 4 期
- 状态
- 尚未招募
- 发起方
- 入组人数
- 150
- 主要终点
- Primary endpoint (proportion with a Total Morbidity Score)
研究概览
简要总结
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
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
We will use a centralised internet-based computer-generated randomisation schedule prepared and overseen by an experienced statistician. Patients will be randomised in a 1:1 ratio in permuted blocks of two to six and stratified by country, sex, and adjunctive dexamethasone treatment (yes/no).
入排标准
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
Active arm
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).
干预措施: Acyclovir 50 MG/ML (Drug)
Placebo
Randomisation to 7 days of IV and/or oral placebo.
干预措施: Placebo (Drug)
结局指标
主要结局
Primary endpoint (proportion with a Total Morbidity Score)
时间窗: 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.
次要结局
- Secondary endpoint 3 All-cause mortality(7 days, 3 months, and 12 months since randomisation)
- Secondary endpoint 1 (Proportion of patients with ≤50% reduction of Total Morbidity Score)(7 days since randomisation)
- Secondary endpoint 2 Extended Glasgow outcome scale score(7 days, 3 months, and 12 months since randomisation)
- Secondary endpoint 4 EQ-5D-5L(7 days, 3 months, and 12 months since randomisation)
- Secondary endpoint 5 Mental Fatigue Scale(7 days, 3 months, and 12 months since randomisation)
- Secondary endpoint 6 (SF-36)(7 days, 3 months, and 12 months since randomisation)
- Secondary outcome 7 neurological deficit(7 days, 3 months, and 12 months since randomisation)
- Secondary outcome 8 Completion of assigned treatment(7 days since randomisation)
- Secondary outcome 9 complications(7 days since randomisation)
- Secondary outcome 10Severe adverse events(7 days since randomisation)
研究者
Jacob Bodilsen
Sponsor-investigator
Aalborg University Hospital