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

October 28, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)

A Randomized Blinded Trial To Evaluate the Safety and Tolerance of High Versus Low Dose Zidovudine Administered to Children With Human Immunodeficiency Virus

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

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.

All participants are randomized to receive AZT at 1 of 2 doses. Patients are stratified according to whether CD4 cell counts are > or < 500 cells/mm3 as well as whether symptoms are mild to moderate or if patients have lymphocytic interstitial pneumonitis (LIP). Medication is dispensed every other week for the first 8 weeks and monthly until week 104, then either monthly or every 3 months. Safety and effectiveness of the treatment program are evaluated at 6-month intervals to assess whether it is appropriate to continue the study as originally designed. Patients are evaluated every 2 weeks for the first 8 weeks, monthly until week 104, every 3 months until week 208, and then every 6 months thereafter.

Study Type

Interventional

Enrollment

400

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Puerto Rico
      • Bayamon, Puerto Rico, 00619
        • Ramon Ruiz Arnau Univ Hosp / Pediatrics
      • San Juan, Puerto Rico, 009367344
        • San Juan City Hosp
      • San Juan, Puerto Rico, 00936
        • UPR Children's Hosp / San Juan City Hosp
  • United States
    • California
      • Downey, California, United States, 902422814
        • Kaiser Permanente / UCLA Med Ctr
      • Long Beach, California, United States, 90801
        • Long Beach Memorial (Pediatric)
      • Los Angeles, California, United States, 900276016
        • Children's Hosp of Los Angeles/UCLA Med Ctr
      • Los Angeles, California, United States, 90033
        • Los Angeles County - USC Med Ctr
      • Los Angeles, California, United States, 900481804
        • Cedars Sinai / UCLA Med Ctr
      • Los Angeles, California, United States, 900951752
        • UCLA Med Ctr / Pediatric
      • Oakland, California, United States, 946091809
        • Children's Hosp of Oakland
      • San Diego, California, United States, 921036325
        • Univ of California / San Diego Treatment Ctr
      • San Francisco, California, United States, 94143
        • Northern California Pediatric AIDS Treatment Ctr / UCSF
    • Connecticut
      • Farmington, Connecticut, United States, 06032
        • Univ of Connecticut Health Ctr / Pediatrics
    • District of Columbia
      • Washington, District of Columbia, United States, 20010
        • Children's Natl Med Ctr
    • Florida
      • Fort Lauderdale, Florida, United States, 33308
        • Ctr for Special Immunology
      • Miami, Florida, United States, 33136
        • Univ of Miami School of Medicine
    • Georgia
      • Atlanta, Georgia, United States, 30303
        • Emory Univ School of Medicine
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Cook County Hosp
      • Chicago, Illinois, United States, 606143394
        • Chicago Children's Memorial Hosp
      • Chicago, Illinois, United States, 60612
        • Univ of Illinois College of Medicine
    • Maryland
      • Baltimore, Maryland, United States, 21201
        • Univ of Maryland at Baltimore / Univ Med Ctr
      • Baltimore, Maryland, United States, 212874933
        • Johns Hopkins Hosp - Pediatric
    • Massachusetts
      • Boston, Massachusetts, United States, 02118
        • Boston Med Ctr
      • Boston, Massachusetts, United States, 021155724
        • Children's Hosp of Boston
      • Worcester, Massachusetts, United States, 01655
        • Univ of Massachusetts Med Ctr
    • New Jersey
      • Newark, New Jersey, United States, 071072198
        • Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl
    • New York
      • Bronx, New York, United States, 10461
        • Albert Einstein College of Medicine
      • Bronx, New York, United States, 10451
        • Lincoln Hosp Ctr / Pediatrics
      • Bronx, New York, United States, 10456
        • Bronx Lebanon Hosp Ctr
      • Brooklyn, New York, United States, 11203
        • SUNY / Health Sciences Ctr at Brooklyn / Pediatrics
      • Jamaica, New York, United States, 11432
        • Jewish Hosp Ctr of Long Island / Pediatrics
      • New Hyde Park, New York, United States, 11042
        • Schneider Children's Hosp / Long Island Jewish Med Ctr
      • New York, New York, United States, 10016
        • Bellevue Hosp / New York Univ Med Ctr
      • New York, New York, United States, 10025
        • Saint Luke's - Roosevelt Hosp Ctr
      • New York, New York, United States, 10029
        • Mount Sinai Med Ctr
      • New York, New York, United States, 10029
        • Metropolitan Hosp Ctr
      • New York, New York, United States, 10021
        • Cornell Univ Med College
      • New York, New York, United States, 10037
        • Harlem Hosp Ctr
      • New York, New York, United States, 10003
        • Beth Israel Med Ctr / Pediatrics
      • New York, New York, United States, 10032
        • Columbia Univ Babies' Hosp
      • Rochester, New York, United States, 14642
        • Univ of Rochester Medical Center
      • Valhalla, New York, United States, 10595
        • Westchester Hosp / New York Med College / Pediatrics
    • North Carolina
      • Chapel Hill, North Carolina, United States, 275997215
        • Univ of North Carolina
      • Durham, North Carolina, United States, 277103499
        • Duke Univ Med Ctr
      • Winston-Salem, North Carolina, United States, 27103
        • Bowman Gray School of Medicine / North Carolina Baptist Hosp
    • Ohio
      • Cincinnati, Ohio, United States, 452670405
        • Holmes Hosp / Univ of Cincinnati Med Ctr
      • Columbus, Ohio, United States, 432052696
        • Columbus Children's Hosp
    • Pennsylvania
      • Pittsburgh, Pennsylvania, United States, 15219
        • Hemophilia Ctr of Western PA / Univ of Pittsburgh
    • South Carolina
      • West Columbia, South Carolina, United States, 29169
        • Julio Arroyo
    • Texas
      • Houston, Texas, United States, 77030
        • Hermann Hosp / Univ Texas Health Science Ctr
      • Houston, Texas, United States, 77030
        • Texas Children's Hosp / Baylor Univ

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

3 months to 12 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Concurrent Medication:

AMENDED:

  • 03-19-91 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:

  • 9/17/90 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.

Prior Medication:

Allowed:

  • Aerosol ribavirin.

Exclusion Criteria

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:

  • 03-19-91 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).
  • Immunoglobulin therapy not specifically allowed.
  • Ketoconazole, acyclovir, or nystatin for prophylaxis.
  • Drugs that are metabolized by hepatic glucuronidation and might alter metabolism of zidovudine (AZT).

Patients with the following 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.

Prior Medication:

Excluded within 2 weeks of study entry:

  • Any other experimental therapy or drugs that cause prolonged neutropenia or significant nephrotoxicity.

Excluded within 1 month of study entry:

  • Antiretroviral agents.
  • Immunomodulating agents including immunoglobulin, interferon, isoprinosine, and IL-2.

Excluded within 2 months of study entry:

  • Systemic ribavirin for retroviral therapy.

Prior Treatment:

Excluded within 1 month of study entry:

  • Lymphocyte or red blood cell transfusions.

Active alcohol or drug abuse.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborators

Glaxo Wellcome

Investigators

  • Study Chair: M Brady
  • Study Chair: P Weintrub

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Completion (Actual)

December 1, 1994

Study Registration Dates

First Submitted

November 2, 1999

First Submitted That Met QC Criteria

August 30, 2001

First Posted (Estimate)

August 31, 2001

Study Record Updates

Last Update Posted (Actual)

November 4, 2021

Last Update Submitted That Met QC Criteria

October 28, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 128
  • 11103 (DAIDS ES Registry Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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