Phase III Randomized Study of Oral Acyclovir in Infants With Herpes Simplex Virus Infection Involving the Central Nervous System

Condition(s) targeted: Herpes Simplex

Intervention: acyclovir (Drug)

Phase: Phase 3

Status: Recruiting

Sponsored by: National Center for Research Resources (NCRR)

Official(s) and/or principal investigator(s):
David W. Kimberlin, Study Chair, Affiliation: University of Alabama at Birmingham

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.

Study design: Treatment

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.

Minimum age: N/A. Maximum age: 28 Days. Gender(s): 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

Children's Hospital of Alabama, Birmingham, Alabama 35233, United States; Recruiting
Richard J. Whitley, Phone: 205-934-5316

University of Alabama Comprehensive Cancer Center, Birmingham, Alabama 35294, United States; Recruiting
David W. Kimberlin, Phone: 205-939-6097

University of Alberta, Edmonton, Alberta T6G 2R7, Canada; Recruiting
Joan Robinson, Phone: 780-492-1680

University of Arkansas, Little Rock, Arkansas 72202, United States; Recruiting
Richard Jacobs, Phone: 501-320-1416

University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205, United States; Recruiting
Elias J. Anaissie, Phone: 501-686-8274

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
John Bradley, Phone: 619-576-5823

Stanford University, Stanford, California 94305, United States; Recruiting
Ann Arvin, Phone: 650-723-5682

Connecticut Children's Medical Center, Hartford, Connecticut 06106, United States; Recruiting
Alberto Cohen-Abbo, Phone: 860-545-9330

University of Florida Health Science Center - Jacksonville, Jacksonville, Florida 32209, United States; Active, not recruiting

Tulane University Medical Center, New Orleans, Louisiana 70112, United States; Recruiting
Rusell Van Dyke, Phone: 504-588-5422

Maine Medical Center, Portland, Maine 04102, United States; Recruiting
Carol McCarthy, Phone: 207-828-8226

University of Manitoba-Winnipeg, Winnipeg, Manitoba R3A 1R9, Canada; Recruiting
Amin Kabani, Phone: 204-787-1928

University of Mississippi Medical Center, Jackson, Mississippi 39216-4505, United States; Recruiting
April Palmer, Phone: 601-984-5206

St. Louis Children's Hospital, Saint Louis, Missouri 63110, United States; Recruiting
Gregory Storch, Phone: 314-454-6079

State University of New York - Upstate Medical University, Syracuse, New York 13210, United States; Recruiting
Leonard Weiner, Phone: 315-464-6331

Carolinas Medical Center, Charlotte, North Carolina 28232-2861, United States; Recruiting
Amina Ahmed, Phone: 704-355-1301

Children's Hospital Medical Center - Cincinnati, Cincinnati, Ohio 45229-3039, United States; Recruiting
Lawrence Stanberry, Phone: 513-559-6773

MetroHealth Medical Center, Cleveland, Ohio 44109, United States; Recruiting
Mary Lou Kumar, Phone: 216-778-4284

Ohio State University Children's Hospital, Columbus, Ohio 43205-2696, United States; Recruiting
Dwight Powell, Phone: 614-722-4450

Rhode Island Hospital, Providence, Rhode Island 02903, United States; Recruiting
Penelope H. Dennehy, Phone: 401-444-4298

Medical University of South Carolina, Charleston, South Carolina 29425-0721, United States; Recruiting
Sandra Fowler, Phone: 843-792-2385

University of Tennessee Medical Center at Knoxville, Knoxville, Tennessee 37920, United States; Recruiting
Thomas Smith, Phone: 423-544-9356

Vanderbilt University, Nashville, Tennessee 37232-6305, United States; Recruiting
Kathy Edwards, Phone: 615-322-2250

Baylor College of Medicine, Houston, Texas 77030, United States; Recruiting
Gail Demmler, Phone: 713-770-4330

Cook Children's Medical Center - Fort Worth, Fort Worth, Texas 76104, United States; Recruiting
Mark Shelton, Phone: 817-885-4000

University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284-7811, United States; Recruiting
Charles Leach, Phone: 210-567-5246

University of Texas Southwestern Medical School, Dallas, Texas 75235-9032, United States; Recruiting
Pablo J. Sanchez, Phone: 214-648-3753

Starting date: June 1997
Last updated: June 23, 2005