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

NCT ID: NCT00031447

Last Updated: 2012-05-16

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 1999-08-31
• Study Completion Date: 2008-04-30

Brief 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.

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.

Conditions

Herpes Simplex

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Placebo

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

Placebo identical to oral acyclovir suspension in appearance and taste.

Acyclovir

Group Type: EXPERIMENTAL

Acyclovir

Intervention Type: DRUG

Oral suspension 300 mg/m\^2/dose, 3 times per day (TID), for 6 months.

Interventions

Acyclovir

Oral suspension 300 mg/m\^2/dose, 3 times per day (TID), for 6 months.

Intervention Type: DRUG

Placebo

Placebo identical to oral acyclovir suspension in appearance and taste.

Intervention Type: DRUG

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.

• Maximum Eligible Age: 28 Days
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

University of Alabama at Birmingham

Birmingham, Alabama, United States

Arkansas Children's Hospital, Department of Infectious Diseases

Little Rock, Arkansas, 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

Washington University School of Medicine in St. Louis - Center for Clinical Studies

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

Cook Children's Infectious Disease Services

Fort Worth, Texas, United States

University of Texas Health Science Center San Antonio - Pediatrics - Immunology & Infectious Disease

San Antonio, Texas, United States

Seattle Children's Hospital - Infectious Diseases

Seattle, Washington, United States

University of Alberta - Aberhart Centre - Pediatrics

Edmonton, Alberta, Canada

Countries

United States; Canada

References

Kimberlin DW, Whitley RJ, Wan W, Powell DA, Storch G, Ahmed A, Palmer A, Sanchez PJ, Jacobs RF, Bradley JS, Robinson JL, Shelton M, Dennehy PH, Leach C, Rathore M, Abughali N, Wright P, Frenkel LM, Brady RC, Van Dyke R, Weiner LB, Guzman-Cottrill J, McCarthy CA, Griffin J, Jester P, Parker M, Lakeman FD, Kuo H, Lee CH, Cloud GA; National Institute of Allergy and Infectious Diseases Collaborative Antiviral Study Group. Oral acyclovir suppression and neurodevelopment after neonatal herpes. N Engl J Med. 2011 Oct 6;365(14):1284-92. doi: 10.1056/NEJMoa1003509.

Reference Type: RESULT

PMID: 21991950 (View on PubMed)

Other Identifiers

CASG 104

Identifier Type: -

Identifier Source: secondary_id

N01AI30025C

Identifier Type: -

Identifier Source: secondary_id

N01AI30025

Identifier Type: NIH

Identifier Source: secondary_id

View Link

97-006

Identifier Type: -

Identifier Source: org_study_id

NCT00001099

Identifier Type: -

Identifier Source: nct_alias