Acyclovir Herpes Simplex Virus (HSV) Skin, Eye, and Mouth
Condition: Herpes Simplex
MeSH terms: Herpes Simplex
Intervention: Acyclovir; Placebo
Intervention description: Oral suspension 300 mg/m^2/dose, 3 times per day (TID), for 6 months.; Placebo identical to oral acyclovir suspension in appearance and taste.
Intervention MeSH terms: Acyclovir
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Care Provider, Investigator)
Enrollment: 29.0
Sex: All
Maximum age: 28 Days
Healthy volunteers: No
Keywords: Herpes Simplex, Acyclovir, Infants

Summary:

      The purpose of this study is to test whether long-term treatment with oral acyclovir improves
      the outcome for infants with herpes simplex virus (HSV) disease of the skin, eyes, and mouth
      (SEM). Study participants will include infants in the United States and Canada who have HSV
      disease of the skin, eyes, and mouth, with no central nervous system disease present.
      Initially, all subjects will be treated with acyclovir administered through IV access
      (through the vein) for 14 days while hospitalized. Participants will then be placed in one of
      two groups, acyclovir given by mouth or a placebo (substance with no medication present). The
      participant and the study site will not know to which group the subject is assigned. All
      children will be followed at 6, 12, 24, 36, 48, and 60 months of age. During the follow up
      visits, physicals, hearing assessments, eye assessments, and neurological assessments will be
      completed.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Isolation by viral culture of herpes simplex virus (HSV)-1or HSV-2 from cutaneous
             lesions, conjunctivae, or oropharynx. Detection of HSV at any of these sites is
             sufficient, and the presence of skin lesions is not required for study enrollment.

          -  Normal cerebrospinal fluid (CSF) indices (<22 white blood cells (WBCs)/mm^3 and
             protein <115 mg/dl for term infants; (<25 WBCs/mm^3 and protein <220 mg/dl for preterm
             infants both at the time of diagnosis of HSV disease and at the time of study
             randomization.

          -  No evidence of HSV central nervous system (CNS) disease by computed tomography (CT)
             with contrast, magnetic resonance imaging (MRI) with gadolinium, or head ultrasound
             (HUS) [NOTE: CT with contrast is the preferred imaging study].

          -  Normal electroencephalogram (EEG), if performed [NOTE: EEG is suggested for the
             evaluation of infants with HSV disease but is not required for this study].

          -  No evidence of visceral dissemination of HSV infection (normal liver function tests,
             normal chest x-ray, etc.).

          -  Negative CSF HSV polymerase chain reaction (PCR) results from specimens obtained both
             within 72 hours of initiation of intravenous acyclovir therapy and within 48 hours
             prior to completion of intravenous acyclovir therapy.

          -  Less than or equal to 28 days of age at the time of initial presentation with skin,
             eyes, and mouth (SEM) disease.

          -  Birth weight greater than or equal to equal to 800 grams.

        Exclusion Criteria:

          -  Infants with either grade 3 or grade 4 intraventricular hemorrhage (IVH) prior to
             study enrollment.

          -  Breast feeding infants whose mothers are taking acyclovir, valacyclovir, or
             famciclovir for >120 hours (>5 days). If at any point following enrollment the mother
             takes these antiviral drugs for >120 hours (>5 days), she will be asked to refrain
             from breast feeding while taking the drug.

          -  Infants known to be born to women who are human immunodeficiency virus (HIV) positive
             (but HIV testing is not required for study entry). These infants are at known risk for
             acquiring HIV, which would alter their immune response to other infections, including
             HSV infection. Additionally, they may be receiving antiretroviral and/or antiviral
             drugs during the time in which the study of suppressive oral acyclovir is being
             conducted. As such, they will be excluded if the mother's positive HIV status is known
             at the time of evaluation for study inclusion. If at any point following enrollment it
             is learned that an infant is HIV positive, he/she will be continued on the study
             protocol.

          -  Infants with either central nervous system (CNS) or disseminated HSV infection.
             Patients with CNS HSV infection will be considered for enrollment and randomization in
             the ongoing Collaborative Antiviral Study Group (CASG) evaluation of oral suppressive
             acyclovir therapy following neonatal HSV infections involving the CNS.

          -  Infants with creatinine >1.5mg/dl at time of study enrollment.

          -  Infants receiving acyclovir expectantly do not qualify for this study because they
             never developed HSV disease. Expectant therapy describes infants who are cultured at
             approximately 24 hours of life because of a risk of HSV infection (i.e. they are born
             to women with active genital lesions). Oftentimes, if these cultures are positive, the
             infant will receive a course of intravenous acyclovir to prevent the development of
             HSV disease. However, since they never actually had HSV disease, their potential
             outcome cannot be compared with infants with typical skin, eyes, and mouth (SEM)
             disease, and so they are not included in this study.