A Randomized, Comparative Trial of Zidovudine (AZT) Versus 2',3'-Didehydro-3'-Deoxythymidine (Stavudine; d4T) in Children With HIV Infection

Condition(s) targeted: HIV Infections

Intervention: Stavudine (Drug); Zidovudine (Drug)

Phase: Phase 2

Status: Completed

Sponsored by: National Institute of Allergy and Infectious Diseases (NIAID)

Official(s) and/or principal investigator(s):
Kline M, Study Chair
Van Dyke R, Study Chair

PRIMARY: To compare the relative safety and tolerance of oral zidovudine (AZT) versus oral stavudine (d4T) in symptomatic HIV-infected children.

SECONDARY: To compare the clinical, virologic, and immunologic responses between the two treatment groups, and to obtain pharmacokinetic data for both drugs.

At present, AZT is considered the drug of choice for initial treatment of most children with HIV infection, although disease progression or drug intolerance is associated with its long-term use. In preliminary studies in children, d4T, another HIV inhibitor, has been well tolerated, although an optimum dose has not been determined.

Official title: A Randomized, Comparative Trial of Zidovudine (AZT) Versus 2',3'-Didehydro-3'-Deoxythymidine (Stavudine; d4T) in Children With HIV Infection

Study design: Treatment, Parallel Assignment, Pharmacokinetics Study

Detailed description: At present, AZT is considered the drug of choice for initial treatment of most children with HIV infection, although disease progression or drug intolerance is associated with its long-term use. In preliminary studies in children, d4T, another HIV inhibitor, has been well tolerated, although an optimum dose has not been determined.

Patients are randomized to receive either oral AZT or oral d4T. Treatment continues until the last patient enrolled has received 52 weeks of therapy, or until the study is terminated.

Minimum age: 3 Months. Maximum age: 6 Years. Gender(s): Both.

Criteria:

Inclusion Criteria

Concurrent Medication:

Recommended:

- PCP prophylaxis.

Allowed:

- Immunoglobulin.

- Erythropoietin, G-CSF, and GM-CSF.

- Corticosteroids.

- Ethionamide or isoniazid for TB if no alternative is available.

- Pyridoxine (up to 50 mg/day) as vitamin supplement.

Patients must have:

- Symptomatic HIV infection.

- No more than 6 weeks of prior antiretroviral or immunomodulator therapy (other than

steroids and IVIG).

- Consent of parent or guardian.

NOTE:

- Coenrollment on another ACTG protocol not involving antiretroviral therapy is

permitted.

Prior Medication:

Allowed:

- Maternal immunomodulator or antiretroviral therapy (including during pregnancy).

- Antiretroviral therapy prior to 2 months.

- Up to 6 weeks of prior antiretroviral therapy or specific immunomodulator therapy

(other than corticosteroids and IVIG).

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

- Current grade 3 or worse neuropathy / lower motor neuropathy.

- Other grade 3 or worse clinical or laboratory toxicities.

- Known intolerance to either AZT or d4T.

Concurrent Medication:

Excluded:

- Chemotherapy for active malignancy.

Patients with the following prior conditions are excluded:

- History of grade 3 or worse neuropathy/lower motor neuropathy.

Prior Medication:

Excluded:

- More than 6 weeks of prior antiretroviral or immunomodulator therapy.

- Antiretroviral or immunomodulator therapy within 7 days prior to study entry. Ongoing

drug or alcohol abuse.

San Juan City Hosp, San Juan 009367344, Puerto Rico

Univ of Puerto Rico / Univ Children's Hosp AIDS, San Juan 009365067, Puerto Rico

Ramon Ruiz Arnau Univ Hosp / Pediatrics, Bayamon 00956, Puerto Rico

Univ of Alabama at Birmingham Schl of Med / Pediatrics, Birmingham, Alabama 35294, United States

UCSF / Moffitt Hosp - Pediatric, San Francisco, California 941430105, United States

UCSD Med Ctr / Pediatrics / Clinical Sciences, La Jolla, California 920930672, United States

Harbor - UCLA Med Ctr / UCLA School of Medicine, Los Angeles, California 905022004, United States

Children's Hosp of Oakland, Oakland, California 946091809, United States

UCLA Med Ctr / Pediatric, Los Angeles, California 900951752, United States

Martin Luther King Jr Gen Hosp / UCLA Med Ctr, Los Angeles, California 900593019, United States

Long Beach Memorial (Pediatric), Long Beach, California 90801, United States

Los Angeles County - USC Med Ctr, Los Angeles, California 90033, United States

Children's Hosp of Denver, Denver, Colorado 802181088, United States

Yale Univ Med School, New Haven, Connecticut 06504, United States

Univ of Connecticut / Farmington, Farmington, Connecticut 06032, United States

Howard Univ Hosp, Washington, District of Columbia 20060, United States

Children's Hosp of Washington DC, Washington, District of Columbia 200102916, United States

Univ of Miami (Pediatric), Miami, Florida 33161, United States

Univ of Florida Health Science Ctr / Pediatrics, Jacksonville, Florida 32209, United States

Emory Univ Hosp / Pediatrics, Atlanta, Georgia 30306, United States

Chicago Children's Memorial Hosp, Chicago, Illinois 606143394, United States

Cook County Hosp, Chicago, Illinois 60612, United States

Univ of Illinois College of Medicine / Pediatrics, Chicago, Illinois 60612, United States

Univ of Chicago Children's Hosp, Chicago, Illinois 606371470, United States

Tulane Univ / Charity Hosp of New Orleans, New Orleans, Louisiana 701122699, United States

Univ of Maryland at Baltimore / Univ Med Ctr, Baltimore, Maryland 21201, United States

Children's Hosp of Boston, Boston, Massachusetts 021155724, United States

Boston City Hosp / Pediatrics, Boston, Massachusetts 02118, United States

Baystate Med Ctr of Springfield, Springfield, Massachusetts 01199, United States

Univ of Massachusetts Med School, Worcester, Massachusetts 016550001, United States

Children's Hosp of Michigan, Detroit, Michigan 48201, United States

UMDNJ - Robert Wood Johnson Med School / Pediatrics, New Brunswick, New Jersey 089030019, United States

Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl, Newark, New Jersey 071072198, United States

Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl, Newark, New Jersey 07103, United States

Cooper Hosp - Univ Med Ctr / UMDNJ - New Jersey Med Schl, Camden, New Jersey 08103, United States

King's County Hosp Ctr / Pediatrics, Brooklyn, New York 11203, United States

Harlem Hosp Ctr, New York, New York 10037, United States

SUNY - Brooklyn, Brooklyn, New York 11203, United States

Cornell Univ Med College, New York, New York 10021, United States

North Shore Univ Hosp, Great Neck, New York 11021, United States

Westchester Hosp, Valhalla, New York 10595, United States

Schneider Children's Hosp, New Hyde Park, New York 11040, United States

Univ of Rochester Medical Center, Rochester, New York 14642, United States

Bellevue Hosp / New York Univ Med Ctr, New York, New York 10016, United States

Columbia Presbyterian Med Ctr, New York, New York 10032, United States

Mount Sinai Med Ctr / Pediatrics, New York, New York 10029, United States

Metropolitan Hosp Ctr, New York, New York 10029, United States

Children's Hosp at Albany Med Ctr, Albany, New York 12208, United States

SUNY Health Sciences Ctr at Syracuse / Pediatrics, Syracuse, New York 13210, United States

Bronx Lebanon Hosp Ctr, Bronx, New York 10457, United States

Incarnation Children's Ctr / Columbia Presbyterian Med Ctr, New York, New York 10032, United States

State Univ of New York at Stony Brook, Stony Brook, New York 117948111, United States

Lincoln Hosp Ctr, Bronx, New York 10451, United States

Beth Israel Med Ctr / Pediatrics, New York, New York 10003, United States

Duke Univ Med Ctr, Durham, North Carolina 277103499, United States

Univ of North Carolina at Chapel Hill / Duke Univ Med Ctr, Durham, North Carolina 27710, United States

Cincinnati Children's Hosp / Univ Hosp, Cincinnati, Ohio 452292899, United States

Columbus Children's Hosp, Columbus, Ohio 432052696, United States

Children's Hosp of Philadelphia, Philadelphia, Pennsylvania 191044318, United States

Saint Christopher's Hosp for Children, Philadelphia, Pennsylvania 191341095, United States

Rhode Island Hosp / Brown Univ, Providence, Rhode Island 02903, United States

Med Univ of South Carolina, Charleston, South Carolina 294253312, United States

Saint Jude Children's Research Hosp of Memphis, Memphis, Tennessee 381052794, United States

Children's Med Ctr of Dallas, Dallas, Texas 75235, United States

Hermann Hosp / Univ Texas Health Science Ctr, Houston, Texas 77030, United States

Texas Children's Hosp / Baylor Univ, Houston, Texas 77030, United States

Children's Hospital & Medical Center / Seattle ACTU, Seattle, Washington 981050371, United States

Click here for more information about Zidovudine

Click here for more information about Stavudine

Related publications:

Kline MW, Fletcher CV, Federici ME, Harris AT, Evans KD, Rutkiewicz VL, Shearer WT, Dunkle LM. Combination therapy with stavudine and didanosine in children with advanced human immunodeficiency virus infection: pharmacokinetic properties, safety, and immunologic and virologic effects. Pediatrics. 1996 Jun;97(6 Pt 1):886-90.

McKinney RE Jr. Ongoing and future trials of antiretroviral therapy in the pediatric AIDS clinical trials group (PACTG). Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:173

Kline MW, Van Dyke RB, Lindsey JC, Gwynne M, Culnane M, McKinney RE Jr, Nichols S, Mitchell WG, Yogev R, Hutcheon N. A randomized comparative trial of stavudine (d4T) versus zidovudine (ZDV, AZT) in children with human immunodeficiency virus infection. AIDS Clinical Trials Group 240 Team. Pediatrics. 1998 Feb;101(2):214-20.

Dankner WM, Lindsey JC, Levin MJ. Correlates of opportunistic infections in children infected with the human immunodeficiency virus managed before highly active antiretroviral therapy. Pediatr Infect Dis J. 2001 Jan;20(1):40-8.

Last updated: June 23, 2005