OBJECTIVES:

I. Determine the efficacy of long term suppressive therapy with oral acyclovir in infants with herpes simplex virus infection limited to skin, eyes, and mouth.

II. Determine the neurologic outcome in these patients when treated with this regimen.

III. Evaluate the significance of a positive cerebrospinal fluid (CSF) polymerase chain reaction (PCR) result when all other CSF parameters remain normal in these patients.

IV. Correlate the time to first positive CSF PCR result in the first 12 months of life with clinical neurological assessment in these patients when treated with this regimen.

V. Determine whether the continuous administration of this drug suppresses recurrent skin lesions in these patients.

VI. 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:  66

PROTOCOL OUTLINE:

This is a randomized, double blind, placebo controlled, multicenter study.

All patients undergo a lumbar puncture and then receive acyclovir IV every 8 hours on Days 1-14. On Day 12, patients may undergo a lumbar puncture (at discretion of investigator). Whole blood is obtained for herpes simplex virus PCR analysis. Upon completion of intravenous therapy, patients with a negative CSF PCR are randomized to one of two treatment arms.

Arm I: Patients receive oral acyclovir three times daily for 6 months.

Arm II: Patients receive placebo three times daily for 6 months.

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 limited to skin, eyes, and mouth; HSV-1 or HSV-2 isolated from cutaneous lesions, conjunctivae, or oropharynx (presence of skin lesions not required); normal CSF indices: WBC less than 22/mm3 and protein less than 115 mg/dL for term infants OR WBC less than 25/mm3 and protein less than 220 mg/dL for preterm infants; no evidence of CNS involvement by CT with contrast, MRI with gadolinium, or head ultrasound; no visceral dissemination (normal liver function tests, normal chest x-ray, etc.); negative CSF PCR result

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; no prior prophylactic acyclovir for risk of herpes simplex virus infection

--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
      University of Alabama Comprehensive Cancer Center, Birmingham,  Alabama,  35294,  United States
Arkansas
      University of Arkansas, Little Rock,  Arkansas,  72202,  United States
      University of Arkansas for Medical Sciences, Little Rock,  Arkansas,  72205,  United States
California
      Cedars-Sinai Medical Center, Los Angeles,  California,  90048,  United States
      Children's Hospital and Health Center, San Diego,  California,  92123-4282,  United States
      Stanford University, Stanford,  California,  94305,  United States
Florida
      University of Florida Health Science Center - Jacksonville, Jacksonville,  Florida,  32209,  United States
Louisiana
      Tulane University Medical Center, New Orleans,  Louisiana,  70112,  United States
Maine
      Maine Medical Center, Portland,  Maine,  04102,  United States
Mississippi
      University of Mississippi Medical Center, Jackson,  Mississippi,  39216-4505,  United States
Missouri
      St. Louis Children's Hospital, Saint Louis,  Missouri,  63110,  United States
New York
      State University of New York - Upstate Medical University, Syracuse,  New York,  13210,  United States
North Carolina
      Carolinas Medical Center, Charlotte,  North Carolina,  28232-2861,  United States
Ohio
      Children's Hospital Medical Center - Cincinnati, Cincinnati,  Ohio,  45229-3039,  United States
      MetroHealth Medical Center, Cleveland,  Ohio,  44109,  United States
      Ohio State University Children's Hospital, Columbus,  Ohio,  43205-2696,  United States
Rhode Island
      Rhode Island Hospital, Providence,  Rhode Island,  02903,  United States
South Carolina
      Medical University of South Carolina, Charleston,  South Carolina,  29425-0721,  United States
Tennessee
      University of Tennessee Medical Center at Knoxville, Knoxville,  Tennessee,  37920,  United States
      Vanderbilt University, Nashville,  Tennessee,  37232-6305,  United States
Texas
      Baylor College of Medicine, Houston,  Texas,  77030,  United States
      Cook Children's Medical Center - Fort Worth, Fort Worth,  Texas,  76104,  United States
      University of Texas Health Science Center at San Antonio, San Antonio,  Texas,  78284-7811,  United States
      University of Texas Southwestern Medical School, Dallas,  Texas,  75235-9032,  United States
Canada, Alberta
      University of Alberta, Edmonton,  Alberta,  T6G 2R7,  Canada
Canada, Manitoba
      University of Manitoba-Winnipeg, Winnipeg,  Manitoba,  R3A 1R9,  Canada

Study chairs or principal investigators

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

Study ID Numbers:  199/15334; UAB-CASG-104
Record last reviewed:  December 2003
Last Updated:  October 13, 2004
Record first received:  August 3, 2000
ClinicalTrials.gov Identifier:  NCT00006135
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08