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

This study has been completed.
Sponsor:
Collaborator:
Glaxo Wellcome
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000983
First received: November 2, 1999
Last updated: March 15, 2012
Last verified: March 2012
  Purpose

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.


Condition Intervention Phase
HIV Infections
Drug: Zidovudine
Phase 2

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Randomized Blinded Trial To Evaluate the Safety and Tolerance of High Versus Low Dose Zidovudine Administered to Children With Human Immunodeficiency Virus

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 400
Study Completion Date: December 1994
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.

  Eligibility

Ages Eligible for Study:   3 Months to 12 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000983

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

Additional Information:
Publications:
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)
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

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000983     History of Changes
Other Study ID Numbers: ACTG 128, 11103
Study First Received: November 2, 1999
Last Updated: March 15, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Acquired Immunodeficiency Syndrome
Zidovudine

Additional relevant MeSH terms:
Acquired Immunodeficiency Syndrome
HIV Infections
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Slow Virus Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Zidovudine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on July 23, 2014