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Acyclovir Herpes Simplex Virus (HSV) Skin, Eye, and Mouth

Information source: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Herpes Simplex

Intervention: Acyclovir (Drug); Placebo (Drug)

Phase: Phase 3

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)


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.

Clinical Details

Official title: A Placebo-Controlled Phase III Evaluation of Suppressive Therapy With Oral Acyclovir Suspension Following Neonatal Herpes Simplex Virus Infections Limited to the Skin, Eye, and Mouth

Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator), Primary Purpose: Treatment

Primary outcome:

Participants With Neurologic Impairment at 12 Months as Measured by a Bayley's Neuro-developmental Assessment.(Motor Scores)

Participants With Neurologic Impairment at 12 Months as Measured by a Bayley's Neuro-developmental Assessment.(Mental Scores)

Secondary outcome:

Detection of Herpes Simplex Virus (HSV) DNA in the Cerebrospinal Fluid (CSF) by Polymerase Chain Reaction (PCR) at Anytime During the Initial 12 Months of Life.

Two or Fewer Episodes of Cutaneous Recurrence of HSV Disease Post-randomization During the Initial 12 Months of Life.

Detailed description: Neonatal herpes simplex virus (HSV) disease complicates approximately one in every 3,000 births in the United States. This study will be a placebo-controlled Phase III evaluation of suppressive therapy with oral Acyclovir suspension following neonatal HSV infections limited to the skin, eyes, and mouth (SEM). This study will evaluate the efficacy of long-term suppressive therapy with oral acyclovir in infants with SEM disease. It will determine if suppressive oral acyclovir therapy improves neurological outcome in infants following SEM disease. Only infants with SEM disease will qualify for this study. After qualifying for the study and obtaining informed consent, the infant will complete 14 days of intravenous (IV) Acyclovir (20 mg/kg/dose given every 8 hours). Patients will be randomized to receive suppressive oral Acyclovir versus placebo only if they continue to meet all study inclusion criteria at the completion of the IV therapy. This study will be double-blinded and placebo controlled. At the time of randomization, the patient will be placed in 1 of 2 groups (oral suppressive Acyclovir versus placebo). If a patient in either group has a cutaneous HSV recurrence, open-label oral Acyclovir (80 mg/kg/day divided into 4 doses per day) will be provided for 5 days. During the time of administration of open-label oral Acyclovir, study drug will be withheld. All children will be followed at 6, 12, 24, 36, 48, and 60 months of age. Physical examination, hearing assessment, and retinal examination will be performed at each follow up visit. Standardized neurologic evaluation will be performed at 12, 24, 36, 48, and 60 months of age.


Minimum age: N/A. Maximum age: 28 Days. Gender(s): Both.


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.

Locations and Contacts

University of Alabama at Birmingham, Birmingham, Alabama 35233, United States

University of Alberta - Aberhart Centre - Pediatrics, Edmonton, Alberta T6R 2C2, Canada

Arkansas Children's Hospital, Department of Infectious Diseases, Little Rock, Arkansas 72202, United States

Rady Children's Hospital San Diego, San Diego, California 92123, United States

Stanford University School of Medicine, Stanford, California 94305-5208, United States

University of Florida - College of Medicine - Jacksonville, Jacksonville, Florida 32209, United States

The University of Chicago - Comer Children's Hospital - Infectious Diseases, Chicago, Illinois 60637, United States

Kosair Children's Hospital, Louisville, Kentucky 40202, United States

Tulane University - Tulane Medical Center - Department of Pediatrics, New Orleans, Louisiana 70112, United States

Maine Medical Center - Department of Pediatric Specialty Care - Infectious Disease, Portland, Maine 04101, United States

Johns Hopkins Hospital, Baltimore, Maryland 21287, United States

Children's Hospital of Michigan - Pediatric Infectious Diseases, Detroit, Michigan 48201, United States

University of Mississippi, Jackson, Mississippi 39216-4505, United States

Washington University School of Medicine in St. Louis - Center for Clinical Studies, St. Louis, Missouri 63110, United States

Mount Sinai Hospital, New York, New York 10029, United States

UNY Upstate Medical University Hospital - Pediatrics, Syracuse, New York 13210, United States

Carolinas Medical Center, Charlotte, North Carolina 28203, United States

Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio 45231, United States

MetroHealth Medical Center - Pediatric Infectious Disease, Cleveland, Ohio 44109-1998, United States

Nationwide Children's Hospital - Infectious Diseases, Columbus, Ohio 43205, United States

Oregon Health and Science University, Portland, Oregon 97201-3098, United States

Rhode Island Hospital, Providence, Rhode Island 02903, United States

Medical University of South Carolina, Charleston, South Carolina 29425, United States

Vanderbilt University, Nashville, Tennessee 37232, United States

University of Texas Southwestern Medical Center, Dallas, Texas 75390-9063, United States

Cook Children's Infectious Disease Services, Fort Worth, Texas 76104, United States

University of Texas Health Science Center San Antonio - Pediatrics - Immunology & Infectious Disease, San Antonio, Texas 78229, United States

Seattle Children's Hospital - Infectious Diseases, Seattle, Washington 98105, United States

Additional Information

Starting date: August 1999
Last updated: May 10, 2012

Page last updated: August 23, 2015

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