Acyclovir for Herpes Infections Involving the Central Nervous System in Neonates

Completed · Phase 3 · Has a placebo group

Conditions studied: Herpes Simplex

In brief

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.

Key facts

Study ID

NCT00031460

Run by

National Institute of Allergy and Infectious Diseases (NIAID)

People needed

46

Starts

1997-12-01

Expected to finish

2008-04-01

Last updated by the study team

2012-05-16

Who can join

Age: any, up to 0. Sex: any. Healthy volunteers: not accepted.

You may qualify if…

• Viral Culture:
• If cutaneous lesions are present, then isolation of Herpes Simplex Virus (HSV)-1 or HSV-2 by viral culture from any site (skin, oropharynx, cerebral spinal fluid [CSF], urine, etc.) will be required for study entry.
• If cutaneous lesions are not present, then viral isolation by culture is adequate for study entry but is not required. In the case of no cutaneous lesions and negative viral cultures, however, the CSF polymerase chain reaction (PCR) must be positive.
• Additional sites from which HSV culture will be attempted include conjunctivae, oropharynx, blood buffy coat, urine, and CSF.
• Evidence for central nervous system (CNS) HSV disease during the acute illness, including one or more of the following:
• Abnormal CSF indices for term infants: greater than 22 white blood cells (WBCs)/mm\^3 and protein greater than 115mg/dl.
• Abnormal CSF indices for preterm infants: greater than 25 WBCs/mm\^3 and protein greater than 220 mg/dl.
• Abnormal neuroimaging study (computed tomography [CT] with contrast, magnetic resonance imaging [MRI] with gadolinium, or head ultrasound) [NOTE: CT with contrast is the preferred imaging study].
• Abnormal electroencephalography (EEG), if performed (NOTE: EEG is suggested for the evaluation of infants with HSV disease but is not required for this study].
• Positive CSF PCR for HSV deoxyribonucleic acid (DNA) [NOTE: If no cutaneous lesions are present and all viral cultures are negative, the CSF PCR must be positive. If lesions are present and are culture-positive, abnormal CNS neurodiagnostic studies or abnormal CSF indices are sufficient for study entry].
• Negative CSF PCR result 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 CNS disease.
• Birth weight greater than or equal to 800 grams.

You may not qualify if…

• Infants with either a grade 3 or grade 4 intraventricular hemorrhage (IHV) prior to study enrollment.
• Breast feeding infants whose mothers are taking acyclovir, valacyclovir, or famciclovir for greater than 120 hours (greater than 5 days). If at any point following enrollment the mother takes these antiviral drugs for greater than 120 hours (greater than 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 of acquiring HIV, which would alter their immune response to other infections, including herpes simplex virus (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, however, he/she will be continued on the study protocol.
• Infants with HSV infection limited to the skin, eyes, or mouth (SEM). Patients with SEM 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 limited to the SEM.
• Infants with creatinine greater than 1.5 mg/dl at time of study enrollment.

Where it is running

• University of Alabama at Birmingham — Birmingham, Alabama, United States
• Arkansas Children's Hospital, Department of Infectious Diseases — Little Rock, Arkansas, United States
• Children's Hospital Los Angeles - Pediatrics Infectious Diseases — Los Angeles, California, United States
• Rady Children's Hospital San Diego — San Diego, California, United States
• Stanford University School of Medicine — Stanford, California, United States
• University of Florida - College of Medicine - Jacksonville — Jacksonville, Florida, United States
• The University of Chicago - Comer Children's Hospital - Infectious Diseases — Chicago, Illinois, United States
• Kosair Children's Hospital — Louisville, Kentucky, United States
• Tulane University - Tulane Medical Center - Department of Pediatrics — New Orleans, Louisiana, United States
• Maine Medical Center - Department of Pediatric Specialty Care - Infectious Disease — Portland, Maine, United States
• Johns Hopkins Hospital — Baltimore, Maryland, United States
• Children's Hospital of Michigan - Pediatric Infectious Diseases — Detroit, Michigan, United States
• University of Mississippi — Jackson, Mississippi, United States
• St. Louis Children's Hospital - Infectious Disease — St Louis, Missouri, United States
• Mount Sinai Hospital — New York, New York, United States
• UNY Upstate Medical University Hospital - Pediatrics — Syracuse, New York, United States
• Carolinas Medical Center — Charlotte, North Carolina, United States
• Cincinnati Children's Hospital Medical Center — Cincinnati, Ohio, United States
• MetroHealth Medical Center - Pediatric Infectious Disease — Cleveland, Ohio, United States
• Nationwide Children's Hospital - Infectious Diseases — Columbus, Ohio, United States
• Oregon Health and Science University — Portland, Oregon, United States
• Rhode Island Hospital — Providence, Rhode Island, United States
• Medical University of South Carolina — Charleston, South Carolina, United States
• Vanderbilt University — Nashville, Tennessee, United States
• University of Texas Southwestern Medical Center — Dallas, Texas, United States

Full record on ClinicalTrials.gov

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