Long Term Treatment of Herpes Simplex Encephalitis (HSE) With Valacyclovir
Condition: Encephalitis
MeSH terms: Herpes Simplex; Encephalitis, Herpes Simplex; Encephalitis
Intervention: Valacyclovir; Placebo
Intervention description: Valacyclovir is a L-valyl ester of acyclovir. Valacyclovir is provided in 500 mg tablets, 4 tablets (500 mg tablets) 3 times a day (every 8 hours) for 90 days.; Placebo (identical to active drug in appearance) 500 mg tablets, 4 tablets 3 times daily for 90 days.
Intervention MeSH terms: Valacyclovir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Enrollment: 91.0
Sex: All
Minimum age: 12 Years
Healthy volunteers: No
Keywords: encephalitis, herpes simplex, valacyclovir

Summary:

      This study involves patients 12 years and older who have been diagnosed with herpes simplex
      encephalitis (HSE) by a specific laboratory test and have completed treatment or are being
      treated with intravenous (given through a needle inserted into a vein) acyclovir. The purpose
      of the study is to determine if treatment with 4 tablets, 500 milligrams each, of
      valacyclovir given 3 times daily by mouth for 90 days is both effective and safe after
      completing intravenous acyclovir treatment and if it can increase survival with or without
      mild impairment of the brain and mental functions. Participants will be assigned to either
      drug or placebo (inactive substance) randomly (by chance). Study procedures will include
      blood samples and lumbar punctures (procedure in which a needle is inserted into the lower
      back to collect cerebral spinal fluid). Subjects will participate for up to 24 months.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Informed consent and/or assent must be obtained from the patient or legal guardian.

          -  Patients with encephalopathy consistent with herpes simplex encephalitis (HSE) whose
             cerebral spinal fluid (or brain biopsy sample) is positive for herpes simplex virus
             (HSV) deoxyribonucleic acid (DNA) by polymerase chain reaction (PCR).

          -  Patients who are receiving and will have completed intravenous (IV) acyclovir (ACV)
             therapy for a minimum duration of 14 days to a maximum of 21 days and a minimum dose
             of 30 mg/kg/day to a maximum of 60 mg/kg/day, or equivalent dose as adjusted for renal
             dysfunction.

          -  Patient is expected to be available for follow-up visits of study drug administration
             and through the 24 month study visit.

          -  Patients who are 12 years of age or older.

          -  Patients who weigh greater than or equal to 45.5kg (100 pounds).

          -  All female patients with childbearing potential must have a negative pregnancy test
             within 72 hours prior to initiation of study drug. If the pregnancy test is positive,
             the patient is ineligible for the study.

          -  Women must be post-menopausal, surgically sterile or willing to use adequate
             contraception (barrier method with spermicide, intrauterine device (IUD), oral
             contraceptives, implant or other licensed hormone method) from time of study
             enrollment through 1 month after the last dose of study treatment.

          -  Men must be surgically sterile or willing to use contraception (barrier method with
             spermicide) from time of study enrollment through 1 month after the last dose of study
             treatment.

        Exclusion Criteria:

          -  Patients with herpes simplex virus (HSV) meningitis only, without evidence of HSV
             encephalitis.

          -  Patients with an anticipated life expectancy < 90 days.

          -  Patients with creatinine clearance of less than or equal to 50ml/min./1.73 m^2.

          -  Pregnant or breastfeeding females.

          -  Patients who have received any anti-herpesvirus medication (e.g. ganciclovir) other
             than intravenous acyclovir (ACV) for acute therapy of the current episode of herpes
             simplex encephalitis (HSE).

          -  Patients who are unable to swallow oral medications at the time of study drug
             randomization (Day 0).

          -  Patients who are > 3 days beyond completion of treatment course with intravenous (IV)
             ACV.

          -  Patients who are expected to receive long-term (> 30 days/year) therapy with antiviral
             medications active against HSV [e.g. ACV, valacyclovir (VACV), famciclovir].