The Safety of Different Dose Levels of Zidovudine in HIV-Infected Children

NCT00000983 | Completed Phase 2

• 2 other identifiers: ACTG 12811103
• Study Type: interventional
• Target: 400
• Locations: 2 countries
• Sites: 51

Brief Summary

To evaluate and compare differences in tolerance and side effects associated with two different dosages of zidovudine (AZT) when used to treat children with HIV infection. Other goals are to evaluate and compare the degree of change in neurodevelopmental disease and determine whether there are differences in the rate and degree of toxicities associated with one versus the other dosage. AZT has been shown to decrease the death rate and frequency of opportunistic infections in certain adult patients with symptomatic HIV infection. Thus, it is likely that symptomatic HIV infected children may also benefit from AZT. Studies of the safety and pharmacokinetics (blood levels) in children have indicated that AZT can be given to children in doses that can be tolerated and that can be assumed to be therapeutic. Those currently taking care of infected children no longer feel it is ethical to conduct an AZT/placebo (inactive substance) trial. In addition, given the information learned from studies of adult patients that shows effectiveness of AZT at lower doses, experience with an equivalent lower dose in children needs to be studied.

Conditions

HIV Infections

Keywords

Acquired Immunodeficiency Syndrome; Zidovudine

Interventions

Zidovudine DRUG

Eligibility Criteria

• Age: 3 Months - 12 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Concurrent Medication:
• AMENDED:
• Prophylaxis for PCP is recommended according to current practice guidelines. As per published recommendations, primary prophylaxis with TMP / SMX on a M-T-W basis is encouraged.
• Allowed:
• Immunoglobulin therapy as single dose exposure prophylaxis or for children with hypogammaglobulinemia.
• Trimethoprim / sulfamethoxazole (TMP / SMX) and parenteral or aerosolized pentamidine for prophylaxis for Pneumocystis carinii pneumonia for children with AIDS and/or CD4+ counts = or \< 500 cells/mm3.
• Systemic ketoconazole and acyclovir, or oral nystatin for acute therapy.
• Aerosol ribavirin for short-term treatment of acute respiratory syncytial virus (RSV).
• AMENDED:
• /17/90 enrollment is limited to children \< 6 years of age.
• Original design:
• Patients must have the following:
• Parent or guardian available to give written informed consent.
• Laboratory evidence of HIV infection.
• Children \< 15 months of age, with CD4+ cell count \> 500 cells/mm3, who are thought to have acquired HIV through perinatal transmission and whose only laboratory evidence of HIV infection is a positive antibody test, must also have one or more of the laboratory criteria described in Disease Status AND one or more of the disease criteria that are required of children \> 15 months old with CD4+ cell counts \> 500 cells/mm3.

You may not qualify if:

• Co-existing Condition:
• Patients with the following conditions or symptoms are excluded:
• Previous AIDS-defining opportunistic infection or neoplasms as specified by the CDC surveillance criteria for AIDS.
• Previous unexplained recurrent, serious bacterial infections (two or more within a 2-year period) including sepsis, meningitis, pneumonia, abscess of an internal organ, and bone/joint infections caused by Haemophilus, Streptococcus, or other pyogenic bacteria.
• Qualifying for entrance criteria to zidovudine (AZT) + or - gammaglobulin (ACTG 051).
• Encephalopathy.
• Failure to thrive (defined as a child who crosses two percentile lines on the growth chart or child who is \< fifth percentile and does not follow curve) and/or oral candidiasis for at least 2 months despite appropriate topical therapy.
• Lymphocytic interstitial pneumonitis (LIP) with steroid dependency or requiring supplemental oxygen.
• Preexisting malignancies.
• Concurrent Medication:
• AMENDED:
• Prophylaxis with antiviral or antifungals agents, except for PCP prophylaxis is prohibited.
• Drugs that are metabolized by hepatic glucuronidation should be used with caution.
• Excluded:
• Prophylaxis for oral candidiasis or otitis media or other infections (sinusitis, urinary tract infections).

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead
• Glaxo Wellcome: collaborator

Study Sites (51)

Kaiser Permanente / UCLA Med Ctr

Downey, California, 902422814, United States

Location

Long Beach Memorial (Pediatric)

Long Beach, California, 90801, United States

Location

Children's Hosp of Los Angeles/UCLA Med Ctr

Los Angeles, California, 900276016, United States

Location

Los Angeles County - USC Med Ctr

Los Angeles, California, 90033, United States

Location

Cedars Sinai / UCLA Med Ctr

Los Angeles, California, 900481804, United States

Location

UCLA Med Ctr / Pediatric

Los Angeles, California, 900951752, United States

Location

Children's Hosp of Oakland

Oakland, California, 946091809, United States

Location

Univ of California / San Diego Treatment Ctr

San Diego, California, 921036325, United States

Location

Northern California Pediatric AIDS Treatment Ctr / UCSF

San Francisco, California, 94143, United States

Location

Univ of Connecticut Health Ctr / Pediatrics

Farmington, Connecticut, 06032, United States

Location

Children's Natl Med Ctr

Washington D.C., District of Columbia, 20010, United States

Location

Ctr for Special Immunology

Fort Lauderdale, Florida, 33308, United States

Location

Univ of Miami School of Medicine

Miami, Florida, 33136, United States

Location

Emory Univ School of Medicine

Atlanta, Georgia, 30303, United States

Location

Cook County Hosp

Chicago, Illinois, 60612, United States

Location

Univ of Illinois College of Medicine

Chicago, Illinois, 60612, United States

Location

Chicago Children's Memorial Hosp

Chicago, Illinois, 606143394, United States

Location

Univ of Maryland at Baltimore / Univ Med Ctr

Baltimore, Maryland, 21201, United States

Location

Johns Hopkins Hosp - Pediatric

Baltimore, Maryland, 212874933, United States

Location

Children's Hosp of Boston

Boston, Massachusetts, 021155724, United States

Location

Boston Med Ctr

Boston, Massachusetts, 02118, United States

Location

Univ of Massachusetts Med Ctr

Worcester, Massachusetts, 01655, United States

Location

Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl

Newark, New Jersey, 071072198, United States

Location

SUNY / Health Sciences Ctr at Brooklyn / Pediatrics

Brooklyn, New York, 11203, United States

Location

Jewish Hosp Ctr of Long Island / Pediatrics

Jamaica, New York, 11432, United States

Location

Schneider Children's Hosp / Long Island Jewish Med Ctr

New Hyde Park, New York, 11042, United States

Location

Beth Israel Med Ctr / Pediatrics

New York, New York, 10003, United States

Location

Bellevue Hosp / New York Univ Med Ctr

New York, New York, 10016, United States

Location

Cornell Univ Med College

New York, New York, 10021, United States

Location

Saint Luke's - Roosevelt Hosp Ctr

New York, New York, 10025, United States

Location

Metropolitan Hosp Ctr

New York, New York, 10029, United States

Location

Mount Sinai Med Ctr

New York, New York, 10029, United States

Location

Columbia Univ Babies' Hosp

New York, New York, 10032, United States

Location

Harlem Hosp Ctr

New York, New York, 10037, United States

Location

Univ of Rochester Medical Center

Rochester, New York, 14642, United States

Location

Lincoln Hosp Ctr / Pediatrics

The Bronx, New York, 10451, United States

Location

Bronx Lebanon Hosp Ctr

The Bronx, New York, 10456, United States

Location

Albert Einstein College of Medicine

The Bronx, New York, 10461, United States

Location

Westchester Hosp / New York Med College / Pediatrics

Valhalla, New York, 10595, United States

Location

Univ of North Carolina

Chapel Hill, North Carolina, 275997215, United States

Location

Duke Univ Med Ctr

Durham, North Carolina, 277103499, United States

Location

Bowman Gray School of Medicine / North Carolina Baptist Hosp

Winston-Salem, North Carolina, 27103, United States

Location

Holmes Hosp / Univ of Cincinnati Med Ctr

Cincinnati, Ohio, 452670405, United States

Location

Columbus Children's Hosp

Columbus, Ohio, 432052696, United States

Location

Hemophilia Ctr of Western PA / Univ of Pittsburgh

Pittsburgh, Pennsylvania, 15219, United States

Location

Julio Arroyo

West Columbia, South Carolina, 29169, United States

Location

Hermann Hosp / Univ Texas Health Science Ctr

Houston, Texas, 77030, United States

Location

Texas Children's Hosp / Baylor Univ

Houston, Texas, 77030, United States

Location

Ramon Ruiz Arnau Univ Hosp / Pediatrics

Bayamón, 00619, Puerto Rico

Location

San Juan City Hosp

San Juan, 009367344, Puerto Rico

Location

UPR Children's Hosp / San Juan City Hosp

San Juan, 00936, Puerto Rico

Location

Related Publications (6)

• Lathey JL, Marschner IC, Kabat B, Spector SA. Deterioration of detectable human immunodeficiency virus serum p24 antigen in samples stored for batch testing. J Clin Microbiol. 1997 Mar;35(3):631-5. doi: 10.1128/jcm.35.3.631-635.1997.

  PMID: 9041402 BACKGROUND

• Fiscus SA, Welles SL, Spector SA, Lathey JL. Length of incubation time for human immunodeficiency virus cultures. J Clin Microbiol. 1995 Jan;33(1):246-7. doi: 10.1128/jcm.33.1.246-247.1995.

  PMID: 7699053 BACKGROUND

• Brady MT, McGrath N, Brouwers P, Gelber R, Fowler MG, Yogev R, Hutton N, Bryson YJ, Mitchell CD, Fikrig S, Borkowsky W, Jimenez E, McSherry G, Rubinstein A, Wilfert CM, McIntosh K, Elkins MM, Weintrub PS. Randomized study of the tolerance and efficacy of high- versus low-dose zidovudine in human immunodeficiency virus-infected children with mild to moderate symptoms (AIDS Clinical Trials Group 128). Pediatric AIDS Clinical Trials Group. J Infect Dis. 1996 May;173(5):1097-106. doi: 10.1093/infdis/173.5.1097.

  PMID: 8627060 BACKGROUND

• Brady M, McGrath N, Brouwers P, Gelber R, Fowler M, Weintrub P. Controlled trial of tolerance and efficacy of zidovudine (ZDV) at standard and low dose in children (ACTG 128). The Pediatric AIDS Clinical Trials Group. Int Conf AIDS. 1994 Aug 7-12;10(1):79 (abstract no 268B)

  BACKGROUND

• Parent D, Ellner J, Hafner R, Williams M, Jacobs P, Hojczyk P. A phase II/III trial of Rifampin (RIF) Ciprofloxach (CIPRO), Clofazimine (CLOF), Ethambutol (ETH), +/- Amikacin (AK) in the treatment (RX) of Disseminated Mycobacterium avium (MA) infection in HIV-infected individuals (PTS). Natl Conf Hum Retroviruses Relat Infect (2nd). 1995 Jan 29-Feb 2:56

  BACKGROUND

• 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.

  PMID: 21037891 BACKGROUND

MeSH Terms

Conditions

HIV Infections; Acquired Immunodeficiency Syndrome

Interventions

Zidovudine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Slow Virus Diseases

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• M Brady

  STUDY CHAIR

• P Weintrub

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Purpose: TREATMENT
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: December 1, 1994
• Last Updated: November 4, 2021

Record last verified: 2021-10

Locations

PR (3); US (48)