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

HIV Infections Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000789
• Other study ID #: ACTG 240
• Secondary ID: 11217
• Status: Completed
• Phase: Phase 2
• Est. completion date: July 1998

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 230
• Est. completion date: July 1998
• Accepts healthy volunteers: No
• Gender: All
• Age group: 3 Months to 6 Years

Eligibility

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.

Related Conditions & MeSH terms

• Acquired Immunodeficiency Syndrome
• Communicable Diseases
• HIV Infections
• Infections

Intervention

Drug:
• Stavudine

• Zidovudine

Locations

Country	Name	City	State
Puerto Rico	Univ. Hosp. Ramón Ruiz Arnau, Dept. of Peds.	Bayamon
Puerto Rico	San Juan City Hosp. PR NICHD CRS	San Juan
Puerto Rico	Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS	San Juan
United States	Children's Hospital at Albany Medical Center, Dept. of Peds.	Albany	New York
United States	Emory Univ. School of Medicine, Dept. of Peds., Div. of Infectious Diseases	Atlanta	Georgia
United States	Univ. of Colorado Denver NICHD CRS	Aurora	Colorado
United States	Univ. of Maryland Med. Ctr., Div. of Ped. Immunology & Rheumatology	Baltimore	Maryland
United States	BMC, Div. of Ped Infectious Diseases	Boston	Massachusetts
United States	HMS - Children's Hosp. Boston, Div. of Infectious Diseases	Boston	Massachusetts
United States	Bronx-Lebanon Hosp. IMPAACT CRS	Bronx	New York
United States	SUNY Downstate Med. Ctr., Children's Hosp. at Downstate NICHD CRS	Brooklyn	New York
United States	Cooper Univ. Hosp.	Camden	New Jersey
United States	UNC at Chapel Hill School of Medicine - Dept. of Peds., Div. of Immunology & Infectious Diseases	Chapel Hill	North Carolina
United States	Med. Univ. of South Carolina, Div. of Ped. Infectious Diseases	Charleston	South Carolina
United States	Chicago Children's CRS	Chicago	Illinois
United States	Cook County Hosp.	Chicago	Illinois
United States	Univ. of Chicago - Dept. of Peds., Div. of Infectious Disease	Chicago	Illinois
United States	Univ. of Illinois College of Medicine at Chicago, Dept. of Peds.	Chicago	Illinois
United States	Children's Med. Ctr. Dallas	Dallas	Texas
United States	Children's Hospital of Michigan NICHD CRS	Detroit	Michigan
United States	DUMC Ped. CRS	Durham	North Carolina
United States	Univ. of Connecticut Health Ctr., Dept. of Ped.	Farmington	Connecticut
United States	North Shore-Long Island Jewish Health System, Dept. of Peds.	Great Neck	New York
United States	Texas Children's Hosp. CRS	Houston	Texas
United States	Univ. of Florida Jacksonville NICHD CRS	Jacksonville	Florida
United States	Long Beach Memorial Med. Ctr., Miller Children's Hosp.	Long Beach	California
United States	UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS	Los Angeles	California
United States	Usc La Nichd Crs	Los Angeles	California
United States	St. Jude/UTHSC CRS	Memphis	Tennessee
United States	Univ. of Miami Ped. Perinatal HIV/AIDS CRS	Miami	Florida
United States	UMDNJ - Robert Wood Johnson	New Brunswick	New Jersey
United States	Yale Univ. School of Medicine - Dept. of Peds., Div. of Infectious Disease	New Haven	Connecticut
United States	Schneider Children's Hosp., Div. of Infectious Diseases	New Hyde Park	New York
United States	Tulane/LSU Maternal/Child CRS	New Orleans	Louisiana
United States	Columbia IMPAACT CRS	New York	New York
United States	Harlem Hosp. Ctr. NY NICHD CRS	New York	New York
United States	Incarnation Children's Ctr.	New York	New York
United States	Metropolitan Hosp. NICHD CRS	New York	New York
United States	NYU Med. Ctr., Dept. of Medicine	New York	New York
United States	Children's Hosp. & Research Ctr. Oakland, Ped. Clinical Research Ctr. & Research Lab.	Oakland	California
United States	St. Joseph's Hosp. & Med. Ctr. of New Jersey	Paterson	New Jersey
United States	St. Christopher's Hosp. for Children	Philadelphia	Pennsylvania
United States	The Children's Hosp. of Philadelphia IMPAACT CRS	Philadelphia	Pennsylvania
United States	Univ. of Rochester ACTG CRS	Rochester	New York
United States	UCSD Maternal, Child, and Adolescent HIV CRS	San Diego	California
United States	UCSF Pediatric AIDS CRS	San Francisco	California
United States	UW School of Medicine - CHRMC	Seattle	Washington
United States	Baystate Health, Baystate Med. Ctr.	Springfield	Massachusetts
United States	SUNY Stony Brook NICHD CRS	Stony Brook	New York
United States	SUNY Upstate Med. Univ., Dept. of Peds.	Syracuse	New York
United States	Harbor - UCLA Med. Ctr. - Dept. of Peds., Div. of Infectious Diseases	Torrance	California
United States	Children's National Med. Ctr., ACTU	Washington	District of Columbia
United States	Howard Univ. Washington DC NICHD CRS	Washington	District of Columbia
United States	WNE Maternal Pediatric Adolescent AIDS CRS	Worcester	Massachusetts

Sponsors (3)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Bristol-Myers Squibb, Glaxo Wellcome

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (4)

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. — View Citation

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. — View Citation

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

Perrier M, Schwarz T, Gonzalez O, Brounts S. Squamous cell carcinoma invading the right temporomandibular joint in a Belgian mare. Can Vet J. 2010 Aug;51(8):885-7. — View Citation