A Randomized Comparative Trial of Zidovudine (AZT) Versus 2',3'-Dideoxyinosine (ddI) Versus AZT Plus ddI in Symptomatic HIV-Infected Children

October 26, 2021 updated by: National Institute of Allergy and Infectious Diseases (NIAID)
To compare the effectiveness of treatment with zidovudine (AZT) compared to didanosine (ddI) and compared to the combination of AZT and ddI as determined by survival and disease progression. To compare the relative safety and tolerance of AZT versus ddI versus AZT plus ddI in symptomatic HIV infected children; to compare the virological and immunological parameters in the three treatment groups. AZT has been shown to delay the progression of AIDS in HIV infected individuals. However, bone marrow toxicity is a frequent adverse effect. Also, HIV resistance to AZT sometimes occurs in patients who initially respond to treatment, but later have progression of the disease. Thus, new drug treatments are needed. Studies of ddI in adults and children indicate some effectiveness of the drug. A direct comparison of AZT and ddI treatment in children has not been made. Combination antiviral treatment (AZT plus ddI) may give added therapeutic benefit to children.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

AZT has been shown to delay the progression of AIDS in HIV infected individuals. However, bone marrow toxicity is a frequent adverse effect. Also, HIV resistance to AZT sometimes occurs in patients who initially respond to treatment, but later have progression of the disease. Thus, new drug treatments are needed. Studies of ddI in adults and children indicate some effectiveness of the drug. A direct comparison of AZT and ddI treatment in children has not been made. Combination antiviral treatment (AZT plus ddI) may give added therapeutic benefit to children.

Patients are placed by random selection into one of three groups to receive either AZT alone, ddI alone, or AZT and ddI. This is a double-blind study: neither patient nor treating physician knows which group patient is in. If patients are receiving either AZT or ddI alone and they develop drug toxicity (after dose reduction), or if HIV disease progresses, the alternative single drug is offered. If patients receiving both drugs develop drug toxicity (despite dose reduction) or if HIV disease progresses, they discontinue study drug and are offered the best alternative therapy. PER AMENDMENT 6/26/95: Initial monotherapy AZT arm is unblinded and no further crossover therapy for any arm is permitted. Patients who reach crossover criteria on initial blinded ddI or AZT+ddI will be unblinded and permanently discontinued from study drugs.

Study Type

Interventional

Enrollment

819

Phase

  • Phase 3

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, 00956
        • Ramon Ruiz Arnau Univ Hosp / Pediatrics
      • San Juan, Puerto Rico, 009367344
        • San Juan City Hosp
      • San Juan, Puerto Rico, 009365067
        • Univ of Puerto Rico / Univ Children's Hosp AIDS
      • San Juan, Puerto Rico, 009365067
        • UPR Children's Hosp / UPR School of Medicine
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Univ of Alabama at Birmingham Schl of Med / Pediatrics
    • California
      • Downey, California, United States, 902422814
        • Kaiser Permanente / UCLA Med Ctr
      • La Jolla, California, United States, 920930672
        • UCSD Med Ctr / Pediatrics / Clinical Sciences
      • Long Beach, California, United States, 90801
        • Long Beach Memorial (Pediatric)
      • 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, 905022004
        • Harbor - UCLA Med Ctr / UCLA School of Medicine
      • Los Angeles, California, United States, 900951752
        • UCLA Med Ctr / Pediatric
      • Oakland, California, United States, 946091809
        • Children's Hosp of Oakland
      • Pasadena, California, United States, 91105
        • Huntington Memorial Hosp / Children's Hosp of Los Angeles
      • San Diego, California, United States, 921036325
        • Univ of California / San Diego Treatment Ctr
      • San Francisco, California, United States, 941430105
        • UCSF / Moffitt Hosp - Pediatric
      • Stanford, California, United States, 943054149
        • Stanford Univ School of Medicine / Pediatrics
    • Colorado
      • Denver, Colorado, United States, 802181088
        • Children's Hosp of Denver
    • Connecticut
      • Farmington, Connecticut, United States, 06032
        • Univ of Connecticut Health Ctr
      • New Haven, Connecticut, United States, 06504
        • Yale Univ Med School
    • District of Columbia
      • Washington, District of Columbia, United States, 200102916
        • Children's Hosp of Washington DC
      • Washington, District of Columbia, United States, 20060
        • Howard Univ Hosp
      • Washington, District of Columbia, United States, 200072197
        • Georgetown Univ Med Ctr
    • Florida
      • Miami, Florida, United States, 33161
        • Univ of Miami (Pediatric)
    • Georgia
      • Atlanta, Georgia, United States, 30306
        • Emory Univ Hosp / Pediatrics
    • Illinois
      • Chicago, Illinois, United States, 60612
        • Cook County Hosp
      • Chicago, Illinois, United States, 606143394
        • Chicago Children's Memorial Hosp
      • Chicago, Illinois, United States, 606371470
        • Univ of Chicago Children's Hosp
      • Chicago, Illinois, United States, 60612
        • Univ of Illinois College of Medicine / Pediatrics
    • 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, 021155724
        • Children's Hosp of Boston
      • Boston, Massachusetts, United States, 02118
        • Boston City Hosp / Pediatrics
      • Springfield, Massachusetts, United States, 01199
        • Baystate Med Ctr of Springfield
      • Worcester, Massachusetts, United States, 01655
        • Univ of Massachusetts Med Ctr
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Children's Hosp of Michigan
    • Missouri
      • Saint Louis, Missouri, United States, 63104
        • St Louis Univ School of Medicine
    • New Jersey
      • New Brunswick, New Jersey, United States, 089030019
        • UMDNJ - Robert Wood Johnson Med School / Pediatrics
      • New Brunswick, New Jersey, United States, 08903
        • Robert Wood Johnson Med School / Hershey Med Ctr
      • Newark, New Jersey, United States, 07103
        • Saint Joseph's Hosp and Med Ctr/UMDNJ - New Jersey Med Schl
      • Newark, New Jersey, United States, 071072198
        • Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl
    • New York
      • Albany, New York, United States, 12208
        • Children's Hosp at Albany Med Ctr
      • Bronx, New York, United States, 10461
        • Albert Einstein College of Medicine
      • Bronx, New York, United States, 10457
        • Bronx Lebanon Hosp Ctr
      • Bronx, New York, United States, 10451
        • Lincoln Hosp Ctr
      • Bronx, New York, United States, 10457
        • Bronx Lebanon Hosp Ctr / Pediatrics
      • Brooklyn, New York, United States, 11203
        • King's County Hosp Ctr / Pediatrics
      • Brooklyn, New York, United States, 11203
        • SUNY - Brooklyn
      • Brooklyn, New York, United States, 11203
        • SUNY / Health Sciences Ctr at Brooklyn / Pediatrics
      • Buffalo, New York, United States, 14222
        • Children's Hosp Pact Prog / Children's Hosp of Buffalo
      • Great Neck, New York, United States, 11021
        • North Shore Univ Hosp
      • New Hyde Park, New York, United States, 11040
        • Schneider Children's Hosp
      • 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
        • Metropolitan Hosp Ctr
      • New York, New York, United States, 10021
        • Cornell Univ Med College
      • New York, New York, United States, 10032
        • Columbia Presbyterian Med Ctr
      • New York, New York, United States, 10032
        • Incarnation Children's Ctr / Columbia Presbyterian Med Ctr
      • New York, New York, United States, 10037
        • Harlem Hosp Ctr
      • New York, New York, United States, 10029
        • Mount Sinai Med Ctr / Pediatrics
      • New York, New York, United States, 10003
        • Beth Israel Med Ctr / Pediatrics
      • Rochester, New York, United States, 14642
        • Univ of Rochester Medical Center
      • Stony Brook, New York, United States, 117948111
        • State Univ of New York at Stony Brook
      • Syracuse, New York, United States, 13210
        • SUNY Health Sciences Ctr at Syracuse / Pediatrics
      • Valhalla, New York, United States, 10595
        • Westchester Hosp
    • North Carolina
      • Chapel Hill, North Carolina, United States, 275997215
        • Univ of North Carolina
      • Durham, North Carolina, United States, 277103499
        • Duke Univ Med Ctr
    • Ohio
      • Cincinnati, Ohio, United States, 452292899
        • Cincinnati Children's Hosp / Univ Hosp
      • Cleveland, Ohio, United States, 44106
        • Case Western Reserve Univ
      • Columbus, Ohio, United States, 432052696
        • Columbus Children's Hosp
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 191044318
        • Children's Hosp of Philadelphia
      • Philadelphia, Pennsylvania, United States, 191341095
        • Saint Christopher's Hosp for Children
      • Pittsburgh, Pennsylvania, United States, 15219
        • Hemophilia Ctr of Western PA / Univ of Pittsburgh
    • Rhode Island
      • Providence, Rhode Island, United States, 02903
        • Rhode Island Hosp / Brown Univ
    • South Carolina
      • Charleston, South Carolina, United States, 29425
        • Med Univ of South Carolina
    • Tennessee
      • Memphis, Tennessee, United States, 381052794
        • Saint Jude Children's Research Hosp of Memphis
    • Texas
      • Dallas, Texas, United States, 75235
        • Children's Med Ctr of Dallas
      • Houston, Texas, United States, 77030
        • Hermann Hosp / Univ Texas Health Science Ctr
      • Houston, Texas, United States, 77030
        • Texas Children's Hosp / Baylor Univ
    • Washington
      • Seattle, Washington, United States, 98105
        • Children's Hosp of Seattle

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 17 years (Child)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria

Concurrent Medication:

Allowed:

  • Acetaminophen, ibuprofen, or aspirin, but not on a continual basis for > 72 hours.
  • Systemic ketoconazole and fluconazole for acute therapy.

Recommended:

  • Prophylaxis for PCP. (Primary prophylaxis with TMP / SMX is encouraged.) IV pentamidine may be used in selected cases if not administered on a weekly basis.

Patients must have the following:

  • HIV infection.
  • Children randomized prior to their eighteenth birthday are eligible. Co-enrollment in either ACTG 179 or 189 is permitted.

Prior Medication:

Allowed:

  • Up to six weeks of antiretroviral or immunomodulator treatment excluding steroids and intravenous immunoglobulin.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

  • Active malignancy.
  • Pancreatitis or history of pancreatitis within one year prior to study entry associated with compatible symptoms.
  • History of uncontrolled seizure disorder.
  • Grade 3 or higher peripheral neuropathy.
  • Cardiomyopathy.

Concurrent Medication:

Excluded:

  • Chemotherapy for malignancy.
  • Oral acidifying agents.
  • Acetaminophen, ibuprofen, or aspirin on a continual basis for > 72 hours.
  • Ketoconazole or fluconazole for prophylaxis.
  • Drugs with potential to cause peripheral neuropathy or pancreatitis should not be given daily for > 4 weeks.

Patients with the following are excluded:

  • Active malignancy.
  • Pancreatitis or history of pancreatitis within one year prior to study entry associated with compatible symptoms.
  • History of uncontrolled seizure disorder.
  • Grade 3 or higher peripheral neuropathy.

Prior Medication:

Excluded:

  • Steroids.
  • Intravenous immunoglobulin.
  • Antiretroviral drugs or specific immunomodulator treatment (excluding steroids and intravenous immunoglobulin) for > 6 weeks and within 7 days prior to study entry.

Prior Treatment:

Excluded:

  • Red blood cell transfusion within four weeks prior to study entry.

Ongoing drug or alcohol use.

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
  • Masking: Double

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

Bristol-Myers Squibb
Glaxo Wellcome

Investigators

  • Study Chair: Baker C
  • Study Chair: Englund J

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)

September 1, 1996

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 2, 2021

Last Update Submitted That Met QC Criteria

October 26, 2021

Last Verified

October 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ACTG 152
  • 11127 (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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