Clinical Trial: Acyclovir for Herpes Infections Involving the Central Nervous System in Neonates

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Placebo-Controlled Phase III Evaluation of Suppressive Therapy With Oral Acyclovir Suspension Following Neonatal Herpes Simplex Virus Infections Involving the Central Ne

Brief Summary: The purpose of this study is to test whether long term treatment with acyclovir given orally (by mouth) improves the outcome for infants with herpes simplex virus infection of the brain or spinal cord (known as the central nervous system [CNS]). Infants with herpes viral infection of the CNS that has or has not spread to other parts of the body will be enrolled in this study. All participants will receive treatment in a hospital for 21 days with acyclovir, given intravenously (by a needle inserted into a vein). Participants will then be divided into two groups: those with CNS disease that has or has not spread to the skin, and those whose viral infection has spread and involves the CNS. Both groups will be randomly assigned to receive either oral acyclovir or placebo (inactive substance) for 6 months. Infants in the US and Canada will participate for 5 years. A physical exam, hearing exam, eye exam, and an evaluation of the nervous system will be performed throughout the study.

Detailed Summary: Neonatal herpes simplex virus (HSV) disease complicates approximately 1 in every 3,000 deliveries in the United States, resulting in an estimated 1, 500 cases annually in this country. HSV-1 and HSV-2 infections in the neonate can manifest as: disseminated disease; central nervous system (CNS) disease; or disease limited to the skin, eyes, and mouth (SEM disease). This study will evaluate the efficacy of long term suppressive therapy with oral acyclovir in infants with CNS disease, with or without evidence of dissemination to other organs (including the skin). It will determine if suppressive oral acyclovir therapy improves neurologic outcome in infants following HSV disease with CNS involvement and address the significance of a positive cerebral spinal fluid (CSF) polymerase chain reaction (PCR) result when all other CSF parameters either remain normal or show improvement. Comparisons will be made between groups with respect to post-randomization time to first positive CSF PCR result during the initial 12 months of life, and results will be correlated with clinical neurological assessments. It will determine if continuous administration of oral acyclovir suspension suppresses recurrent skin lesions in infants following HSV disease with CNS involvement, and it will confirm the safety of long-term administration of oral acyclovir therapy in a cohort of infants with HSV disease with CNS involvement. Finally, the effects of suppressive acyclovir therapy on issues of pharmacoeconomics and family infrastructure will be assessed and quantitated. Infants with CNS disease (with or without evidence of viral dissemination to other organs, such as the skin, liver, and lungs) will qualify for this study. Following a 21 day course of treatment with intravenous (IV) acyclovir, infants with CNS disease, with or without cutaneous involvement, will be randomized to either continuous oral acyclovir or placebo (CNS Sub-Study). Similarly, infants with disseminated disease with CNS invo
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Current Primary Outcome:

  • Participants With Neurologic Impairment at 12 Months as Measured by a Bayley's Neuro-developmental Assessment (Motor Scores). [ Time Frame: At 12 months of life. ]
    Motor scores of all participants completing 6 months of blinded therapy as measured by the Bayleys neuro-developmental assessment at 12 months. Scores are classified as the following: greater than or equal to 115 suggests accelerated performance; 85 - 114 suggests development within normal limits; 70 - 84 suggests mildly delayed development; and less than or equal to 69 suggests significant delayed development.
  • Participants With Neurologic Impairment at 12 Months as Measured by Bayley's Neuro-developmental Assessment.(Mental Scores) [ Time Frame: At 12 months of life. ]
    Mental scores of all subjects completing 6 months of blinded therapy as measured by the Bayleys neuro-developmental assessment at 12 months. Scores are classified as the following: greater than or equal to 115 suggests accelerated performance; 85 - 114 suggests development within normal limits; 70 - 84 suggests mildly delayed development; and less than or equal to 69 suggests significant delayed development.


Original Primary Outcome:

Current Secondary Outcome:

  • Number of Participants With Two or Fewer Episodes of Cutaneous Recurrence of Herpes Simplex Virus (HSV) Disease Post-randomization During the Initial 12 Months of Life. [ Time Frame: post randomization - 12 months ]
    Number of participants experiencing 2 or fewer HSV recurrences during the first 12 months of life as measured by assessments and reports at study visits.
  • Detection of Herpes Simplex Virus (HSV) DNA in the Cerebrospinal Fluid (CSF) by PCR at Anytime During the Initial 12 Months of Life. [ Time Frame: post randomization - 12 months ]
    Number of participants assessed to have a positive herpes simplex virus (HSV) DNA by polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF) at any time during their initial 12 months of life after treatment. The PCR is a technique to help visualize copies of a piece of DNA.


Original Secondary Outcome:

Information By: National Institute of Allergy and Infectious Diseases (NIAID)

Dates:
Date Received: March 6, 2002
Date Started: December 1997
Date Completion:
Last Updated: May 10, 2012
Last Verified: October 2009