Clinical trial NCT00006132: Phase III Randomized Study of Oral Acyclovir in Infants With Herpes Simplex Virus Infection Involving the Central Nervous System
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE3
Conditions: Herpes Simplex
Keywords: herpes simplex virus infection
herpes virus infection
immunologic disorders and infectious disorders
rare disease
viral infection
Lead sponsor: National Center for Research Resources (NCRR)
Sponsor class: NIH
Collaborators: name: University of Alabama at Birmingham
First posted: 2000-08-04
Enrollment: 132
Sex: ALL
Minimum age (years): 0
Maximum age (years): 28
Standard ages: CHILD
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: 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.

Detailed description: 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.

Eligibility 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

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Children's Hospital of Alabama
state: Alabama
city: Birmingham
country: United States
facility: University of Alabama Comprehensive Cancer Center
state: Alabama
city: Little Rock
country: United States
facility: University of Arkansas
state: Arkansas
city: Little Rock
country: United States
facility: University of Arkansas for Medical Sciences
state: Arkansas
city: Los Angeles
country: United States
facility: Cedars-Sinai Medical Center
state: California
city: San Diego
country: United States
facility: Children's Hospital and Health Center
state: California
city: Stanford
country: United States
facility: Stanford University
state: California
city: Hartford
country: United States
facility: Connecticut Children's Medical Center
state: Connecticut
city: Jacksonville
country: United States
facility: University of Florida Health Science Center - Jacksonville
state: Florida
city: New Orleans
country: United States
facility: Tulane University Medical Center
state: Louisiana
city: Portland
country: United States
facility: Maine Medical Center
state: Maine
city: Jackson
country: United States
facility: University of Mississippi Medical Center
state: Mississippi
city: Saint Louis
country: United States
facility: St. Louis Children's Hospital
state: Missouri
city: Syracuse
country: United States
facility: State University of New York - Upstate Medical University
state: New York
city: Charlotte
country: United States
facility: Carolinas Medical Center
state: North Carolina
city: Cincinnati
country: United States
facility: Children's Hospital Medical Center - Cincinnati
state: Ohio
city: Cleveland
country: United States
facility: MetroHealth Medical Center
state: Ohio
city: Columbus
country: United States
facility: Ohio State University Children's Hospital
state: Ohio
city: Providence
country: United States
facility: Rhode Island Hospital
state: Rhode Island
city: Charleston
country: United States
facility: Medical University of South Carolina
state: South Carolina
city: Knoxville
country: United States
facility: University of Tennessee Medical Center at Knoxville
state: Tennessee
city: Nashville
country: United States
facility: Vanderbilt University
state: Tennessee
city: Dallas
country: United States
facility: University of Texas Southwestern Medical School
state: Texas
city: Fort Worth
country: United States
facility: Cook Children's Medical Center - Fort Worth
state: Texas
city: Houston
country: United States
facility: Baylor College of Medicine
state: Texas
city: San Antonio
country: United States
facility: University of Texas Health Science Center at San Antonio
state: Texas
city: Edmonton
country: Canada
facility: University of Alberta
state: Alberta
city: Winnipeg
country: Canada
facility: University of Manitoba-Winnipeg
state: Manitoba
Study officials:
affiliation: University of Alabama at Birmingham
name: David W. Kimberlin
role: STUDY_CHAIR
References: