OBJECTIVES: I. Determine the efficacy of long term suppressive therapy with oral acyclovir in infants with herpes simplex virus infection involving the central nervous system. II. Determine whether neurologic outcome is improved in these patients when treated with this regimen. III. Determine whether continuous administration of this drug suppresses recurrent skin lesions in these patients. IV. Determine the safety of this regimen in these patients.

Condition	Treatment or Intervention	Phase
Herpes Simplex	Drug: acyclovir	Phase III

Further Study Details: 

Expected Total Enrollment:  132

PROTOCOL OUTLINE: This is a randomized, double blind, placebo controlled, multicenter study. Patients are stratified according to disease (CNS disease with or without cutaneous involvement vs disseminated disease with CNS involvement). All patients receive acyclovir IV every 8 hours on days 1-21. On day 19, patients undergo a lumbar puncture and must have a negative CSF PCR to be randomized. If patients have a positive CSF PCR on day 19, they continue to receive acyclovir IV every 8 hours. Treatment continues every 7 days with a repeat CSF PCR on the fifth day until a negative CSF PCR result is achieved. Patients are then randomized to one of two treatment arms. Arm I: Patients receive oral acyclovir three times a day for 6 months. Arm II: Patients receive placebo. In case of cutaneous recurrence during the first 12 months of the study, patients receive open label oral acyclovir (if CSF PCR is negative) or acyclovir IV (if CSF PCR is positive) for 5 days. Patients may or may not continue on study drug following this treatment. Patients are followed at 6, 12, 24, 36, 48, and 60 months of age.

Ages Eligible for Study:  up to  28 Days,  Genders Eligible for Study:  Both

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

• Infants diagnosed with herpes simplex virus infection involving the central nervous system with or without evidence of viral dissemination to other organs (i.e., skin, liver, or lungs) HSV-1 or HSV-2 isolated from cutaneous lesions from any site (skin, oropharynx, cerebrospinal fluid (CSF), urine, etc.) OR Must have positive CSF polymerase chain reaction (PCR) if no cutaneous skin lesions are present and viral cultures are negative No infection limited to skin, eyes, or mouth Evidence of CNS involvement includes one or more of the following: Abnormal CSF indices for term infants (WBC greater than 22/mm3 and protein greater than 115 mg/dL) Abnormal CSF indices for preterm infants (WBC greater than 25/mm3 and protein greater than 220 mg/dL) Abnormal neuroimaging study (CT with contrast, MRI with gadolinium, or head ultrasound) Disseminated disease is defined as one or more of the following: SGPT at least 2.5 times upper limit of normal Pneumonia/pneumonitis Necrotizing enterocolitis Disseminated intravascular coagulopathy
• Birth weight at least 800 grams

--Prior/Concurrent Therapy--

• No concurrent nursing from a mother who is receiving acyclovir, valacyclovir, or famciclovir for longer than 120 hours or 5 days

--Patient Characteristics--

• Renal: Creatinine no greater than 1.5 mg/dL
• Cardiovascular: No prior grade 3 or 4 intraventricular hemorrhage
• Other: No infants known to be born to HIV positive women

Alabama
      Children's Hospital of Alabama, Birmingham,  Alabama,  35233,  United States; Recruiting
      University of Alabama Comprehensive Cancer Center, Birmingham,  Alabama,  35294,  United States; Recruiting
Arkansas
      University of Arkansas, Little Rock,  Arkansas,  72202,  United States; Recruiting
      University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States; Recruiting
California
      Cedars-Sinai Medical Center, Los Angeles,  California,  90048,  United States; Completed
      Children's Hospital and Health Center, San Diego,  California,  92123-4282,  United States; Recruiting
      Stanford University, Stanford,  California,  94305,  United States; Recruiting
Connecticut
      Connecticut Children's Medical Center, Hartford,  Connecticut,  06106,  United States; Recruiting
Florida
      University of Florida Health Science Center - Jacksonville, Jacksonville,  Florida,  32209,  United States; No longer recruiting
Louisiana
      Tulane University Medical Center, New Orleans,  Louisiana,  70112,  United States; Recruiting
Maine
      Maine Medical Center, Portland,  Maine,  04102,  United States; Recruiting
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States; Recruiting
Missouri
      St. Louis Children's Hospital, Saint Louis,  Missouri,  63110,  United States; Recruiting
New York
      State University of New York - Upstate Medical University, Syracuse,  New York,  13210,  United States; Recruiting
North Carolina
      Carolinas Medical Center, Charlotte,  North Carolina,  28232-2861,  United States; Recruiting
Ohio
      Children's Hospital Medical Center - Cincinnati, Cincinnati,  Ohio,  45229-3039,  United States; Recruiting
      MetroHealth Medical Center, Cleveland,  Ohio,  44109,  United States; Recruiting
      Ohio State University Children's Hospital, Columbus,  Ohio,  43205-2696,  United States; Recruiting
Rhode Island
      Rhode Island Hospital, Providence,  Rhode Island,  02903,  United States; Recruiting
South Carolina
      Medical University of South Carolina, Charleston,  South Carolina,  29425-0721,  United States; Recruiting
Tennessee
      University of Tennessee Medical Center at Knoxville, Knoxville,  Tennessee,  37920,  United States; Recruiting
      Vanderbilt University, Nashville,  Tennessee,  37232-6305,  United States; Recruiting
Texas
      Baylor College of Medicine, Houston,  Texas,  77030,  United States; Recruiting
      Cook Children's Medical Center - Fort Worth, Fort Worth,  Texas,  76104,  United States; Recruiting
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78284-7811,  United States; Recruiting
      University of Texas Southwestern Medical School, Dallas,  Texas,  75235-9032,  United States; Recruiting
Canada, Alberta
      University of Alberta, Edmonton,  Alberta,  T6G 2R7,  Canada; Recruiting
Canada, Manitoba
      University of Manitoba-Winnipeg, Winnipeg,  Manitoba,  R3A 1R9,  Canada; Recruiting

Study chairs or principal investigators

David W. Kimberlin,  Study Chair,  UAB Comprehensive Cancer Center   

Study ID Numbers:  199/15325; UAB-CASG-103
Record last reviewed:  December 2003
Last Updated:  March 2, 2005
Record first received:  August 3, 2000
ClinicalTrials.gov Identifier:  NCT00006132
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08