Acyclovir Herpes Simplex Virus (HSV) Skin, Eye, and Mouth
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
4 other identifiers
interventional
29
2 countries
28
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.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_3
Started Aug 1999
Longer than P75 for phase_3
28 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
Click on a node to explore related trials.
Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 1, 1999
CompletedFirst Submitted
Initial submission to the registry
March 6, 2002
CompletedFirst Posted
Study publicly available on registry
March 7, 2002
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2008
CompletedStudy Completion
Last participant's last visit for all outcomes
April 1, 2008
CompletedResults Posted
Study results publicly available
April 9, 2010
CompletedMay 16, 2012
November 1, 2009
8.5 years
March 6, 2002
April 1, 2009
May 10, 2012
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
Participants With Neurologic Impairment at 12 Months as Measured by a Bayley's Neuro-developmental Assessment.(Motor Scores)
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.
At 12 months of life.
Participants With Neurologic Impairment at 12 Months as Measured by a Bayley's Neuro-developmental Assessment.(Mental Scores)
Mental 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: less 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.
At 12 months of life.
Secondary Outcomes (2)
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.
post randomization at 12 months
Two or Fewer Episodes of Cutaneous Recurrence of HSV Disease Post-randomization During the Initial 12 Months of Life.
post randomization - 12 months
Study Arms (2)
Placebo
PLACEBO COMPARATORAcyclovir
EXPERIMENTALInterventions
Eligibility Criteria
You may qualify if:
- 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.
You may not qualify if:
- 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 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.
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (28)
University of Alabama at Birmingham
Birmingham, Alabama, 35233, United States
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
University of Alberta - Aberhart Centre - Pediatrics
Edmonton, Alberta, T6R 2C2, Canada
Related Publications (1)
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.
PMID: 21991950RESULT
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Results Point of Contact
- Title
- Penelope M Jester
- Organization
- Collaborative Antiviral Study Group
Publication Agreements
- PI is Sponsor Employee
- No
- Restrictive Agreement
- No
Study Design
- Study Type
- interventional
- Phase
- phase 3
- Allocation
- RANDOMIZED
- Masking
- TRIPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR
- Purpose
- TREATMENT
- Intervention Model
- PARALLEL
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
March 6, 2002
First Posted
March 7, 2002
Study Start
August 1, 1999
Primary Completion
February 1, 2008
Study Completion
April 1, 2008
Last Updated
May 16, 2012
Results First Posted
April 9, 2010
Record last verified: 2009-11