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NCT00000983

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

Last Updated: 2021-11-04

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE2

Total Enrollment

400 participants

Study Classification

INTERVENTIONAL

Study Completion Date

1994-12-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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HIV Infections

Keywords

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Acquired Immunodeficiency Syndrome Zidovudine

Study Design

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Primary Study Purpose

TREATMENT

Interventions

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Zidovudine

Intervention Type DRUG

Eligibility Criteria

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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.

Minimum Eligible Age

3 Months

Maximum Eligible Age

12 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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M Brady

Role: STUDY_CHAIR

P Weintrub

Role: STUDY_CHAIR

Locations

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Kaiser Permanente / UCLA Med Ctr

Downey, California, United States

Site Status

Long Beach Memorial (Pediatric)

Long Beach, California, United States

Site Status

Children's Hosp of Los Angeles/UCLA Med Ctr

Los Angeles, California, United States

Site Status

Los Angeles County - USC Med Ctr

Los Angeles, California, United States

Site Status

Cedars Sinai / UCLA Med Ctr

Los Angeles, California, United States

Site Status

UCLA Med Ctr / Pediatric

Los Angeles, California, United States

Site Status

Children's Hosp of Oakland

Oakland, California, United States

Site Status

Univ of California / San Diego Treatment Ctr

San Diego, California, United States

Site Status

Northern California Pediatric AIDS Treatment Ctr / UCSF

San Francisco, California, United States

Site Status

Univ of Connecticut Health Ctr / Pediatrics

Farmington, Connecticut, United States

Site Status

Children's Natl Med Ctr

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

Site Status

Ctr for Special Immunology

Fort Lauderdale, Florida, United States

Site Status

Univ of Miami School of Medicine

Miami, Florida, United States

Site Status

Emory Univ School of Medicine

Atlanta, Georgia, United States

Site Status

Cook County Hosp

Chicago, Illinois, United States

Site Status

Univ of Illinois College of Medicine

Chicago, Illinois, United States

Site Status

Chicago Children's Memorial Hosp

Chicago, Illinois, United States

Site Status

Univ of Maryland at Baltimore / Univ Med Ctr

Baltimore, Maryland, United States

Site Status

Johns Hopkins Hosp - Pediatric

Baltimore, Maryland, United States

Site Status

Children's Hosp of Boston

Boston, Massachusetts, United States

Site Status

Boston Med Ctr

Boston, Massachusetts, United States

Site Status

Univ of Massachusetts Med Ctr

Worcester, Massachusetts, United States

Site Status

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

Newark, New Jersey, United States

Site Status

SUNY / Health Sciences Ctr at Brooklyn / Pediatrics

Brooklyn, New York, United States

Site Status

Jewish Hosp Ctr of Long Island / Pediatrics

Jamaica, New York, United States

Site Status