The Safety and Effectiveness of Zidovudine in the Treatment of HIV-Infected Children With Mild to Moderate Symptoms

NCT ID: NCT00000990

Last Updated: 2021-11-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 224 participants
• Study Classification: INTERVENTIONAL
• Study Completion Date: 1992-09-30

Brief Summary

To determine the safety and usefulness of zidovudine (AZT) for the treatment of children 3 months to 12 years of age. This study is designed to determine if children who are infected with HIV and who have a special type of lung disease called lymphocytic interstitial pneumonitis (LIP) or other early symptoms of HIV infection may derive benefit from treatment with AZT. It is hoped that this drug will prevent children from developing additional symptoms and infections and will help resolve already existing symptoms.

AZT has been shown in the laboratory to inhibit the infection of cells by HIV. AZT has been shown to decrease the mortality and the frequency of opportunistic infections in certain adult patients with symptomatic HIV infection. It is, therefore, likely that symptomatic HIV-infected children may also benefit from specific antiviral therapy.

Detailed Description

AZT has been shown in the laboratory to inhibit the infection of cells by HIV. AZT has been shown to decrease the mortality and the frequency of opportunistic infections in certain adult patients with symptomatic HIV infection. It is, therefore, likely that symptomatic HIV-infected children may also benefit from specific antiviral therapy.

Children who participate in the study are evaluated at a hospital outpatient clinic and are under the care of a specialist in pediatrics. Of the children who participate in the study, half receive AZT syrup and half receive a placebo (sugar solution). The investigator does not know which medication each child receives as this is decided by a random process. The children take the medication in a strawberry-flavored clear syrup every 6 hours (4 times a day), for a period of 2 years or 104 weeks. The children are monitored on an outpatient basis while receiving therapy and the tests performed on admission to the study are repeated several times during treatment. Blood samples are obtained once a week for the first 4 weeks, every other week for the next 4 weeks, and then monthly until the end of the study. At certain sites, Cerebrospinal fluid (CSF) is collected by lumbar puncture every 52 weeks to evaluate infection involving the brain and nervous system. An independent committee reviews the data collected on the children every 6 months. The drug is stopped or the dose reduced if unacceptable side effects develop. AMENDED: As of August 7, 1989 the study blind was broken, the placebo arm discontinued and the study closed to accrual as of September 25, 1989. The 6 children enrolled in the study have been offered AZT.

Conditions

HIV Infections

Keywords

AIDS-Related Opportunistic Infections; Pulmonary Fibrosis; Zidovudine

Study Design

• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Interventions

Zidovudine

Intervention Type: DRUG

Eligibility Criteria

Inclusion Criteria

Concurrent Medication:

Allowed:

• Prophylaxis for Pneumocystis carinii pneumonia (PCP) in children with AIDS or CD4 cell count = or < 500 cells/mm3.

Children must demonstrate the following clinical and laboratory findings:

• Laboratory evidence of HIV infection as demonstrated by either a positive viral culture or detectable serum p24 antigen or = or > two positive tests for HIV antibody, which must be determined by a federally licensed ELISA test and confirmed by Western blot.
• Children < 15 months of age, 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 following laboratory criteria indicative of immunologic abnormality:
• hypergammaglobulinemia (IgG or IgA) defined as greater than the upper limit of normal for age-adjusted normals; absolute depression in the CD4+ cells to = or < 500 cells/mm3; decreased helper/suppressor ratio < 1.0; depressed in vitro mitogen response to at least one antigen/mitogen.

Exclusion Criteria

• Hemophiliacs are included.

Co-existing Condition:

Children will be excluded for the following reasons:

• Recurrent or life-threatening toxicity. Several allergic reactions such as exfoliative erythroderma, anaphylaxis, or vascular collapse. The presence of one or more of the indicator diseases of AIDS, such as opportunistic infections, malignancy, recurrent bacterial infections, or encephalopathy. Development of two or more episodes of recurrent varicella zoster infection or chronic zoster defined as = or > 30 days duration. Development of AIDS related complex, with failure to thrive, persistent or recurrent oral candidiasis, plus at least one of the following:
• Diarrhea that is either persistent or recurrent, lymphadenopathy at two or more noncontiguous sites, organomegaly, nephropathy manifested by nephrotic syndrome without evidence of renal failure, two or more episodes of herpes stomatitis or one or more episodes of herpes zoster within a 1 year period; plus at least one of the following:
• hypergammaglobulinemia, depression in the CD4+ cells to = or < 500/mm3, decreased helper/suppressor ratio < 1.0, depressed in vitro mitogen response to at least one antigen/mitogen.

Concurrent Medication:

Excluded:

• Hepatotoxic drugs.
• Steroids for lymphocytic interstitial pneumonitis (LIP).
• Prophylaxis for oral candidiasis, or otitis media.
• Immunoglobulin therapy.
• Chronic use of drugs that are metabolized by hepatic glucuronidation.

Concurrent Treatment:

Excluded:

• Supplemental oxygen treatment for lymphocytic interstitial pneumonitis (LIP).

Children will be excluded from the study for the following reasons:

• AIDS-defining opportunistic infection or neoplasm.
• Unexplained recurrent, serious bacterial infections (= or > 2 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.
• Encephalopathy.
• One or both of the following:
• Failure to thrive, defined as a child who crosses two percentile lines on the growth chart or a child who is less than the fifth percentile and does not follow the curve; and/or persistent (= or > 2 months) oral candidiasis despite appropriate topical therapy.
• Children with lymphocytic interstitial pneumonitis (LIP) who are steroid dependent or requiring supplemental oxygen or who have a pretreatment PaO2 < 70 mmHg.
• Children who qualify for the entrance criteria to open-label zidovudine (AZT) or AZT plus or minus gammaglobulin.

Prior Medication:

Excluded:

• Rifampin or rifampin derivatives.
• Antiretroviral agents.
• Zidovudine (AZT).
• Excluded within 2 weeks of study entry:
• Other experimental therapy.
• Drugs which cause prolonged neutropenia or significant nephrotoxicity.
• Excluded within 4 weeks of study entry:
• Immunomodulating agents including immunoglobulin, interferon, isoprinosine, and IL-2.

Prior Treatment:

Excluded within 4 weeks of study entry:

• Lymphocyte transfusions.

Active alcohol or drug abuse.

• Minimum Eligible Age: 3 Months
• Maximum Eligible Age: 12 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

P Weintrub

Role: STUDY_CHAIR

Locations

Kaiser Permanente / UCLA Med Ctr

Downey, California, United States

Long Beach Memorial (Pediatric)

Long Beach, California, United States

Children's Hosp of Los Angeles/UCLA Med Ctr

Los Angeles, California, United States

Martin Luther King Jr Gen Hosp / UCLA Med Ctr

Los Angeles, California, United States

UCLA Med Ctr / Pediatric

Los Angeles, California, United States

Harbor - UCLA Med Ctr / UCLA School of Medicine

Los Angeles, California, United States

Stanford Univ School of Medicine

Menlo Park, California, United States

Children's Hosp of Oakland

Oakland, California, United States

UCSD Treatment Ctr

San Diego, California, United States

Northern California Pediatric AIDS Treatment Ctr / UCSF

San Francisco, California, United States

Univ of Miami School of Medicine

Miami, Florida, United States

Univ of Miami School of Medicine

Miami, Florida, United States

Cook County Hosp

Chicago, Illinois, United States

Chicago Children's Memorial Hosp

Chicago, Illinois, United States

Charity Hosp / Tulane Univ Med School

New Orleans, Louisiana, United States

Tulane Univ School of Medicine

New Orleans, Louisiana, United States

Univ of Maryland at Baltimore / Univ Med Ctr

Baltimore, Maryland, United States

Johns Hopkins Hosp - Pediatric

Baltimore, Maryland, United States

Children's Hosp of Boston

Boston, Massachusetts, United States

Univ of Minnesota

Minneapolis, Minnesota, United States

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

Newark, New Jersey, United States

City Hosp Ctr at Elmhurst / Mount Sinai Hosp

Elmhurst, New York, United States

Beth Israel Med Ctr / Pediatrics

New York, New York, United States

Bellevue Hosp / New York Univ Med Ctr

New York, New York, United States

Mount Sinai Med Ctr

New York, New York, United States

Columbia Univ Babies' Hosp

New York, New York, United States

Harlem Hosp Ctr

New York, New York, United States

Jack Weiler Hosp / Bronx Municipal Hosp

The Bronx, New York, United States

Duke Univ Med Ctr

Durham, North Carolina, United States

Columbus Children's Hosp

Columbus, Ohio, United States

Milton S Hershey Med Ctr

Hershey, Pennsylvania, United States

Baylor College of Medicine

Houston, Texas, United States

Hermann Hosp / Univ Texas Health Science Ctr

Houston, Texas, United States

Countries

United States

Other Identifiers

11026

Identifier Type: REGISTRY

Identifier Source: secondary_id

ACTG 052

Identifier Type: -

Identifier Source: org_study_id