A Study of Zidovudine in Infants Exposed to the HIV Before or Soon After Birth

This study has been completed.
Sponsor:
Collaborator:
Glaxo Wellcome
Information provided by:
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00001007
First received: November 2, 1999
Last updated: July 11, 2008
Last verified: January 2003
  Purpose

To determine if intravenous (IV) and oral zidovudine (AZT) can be safely given to children aged 1 day to 3 months who were born to mothers with an HIV infection. Also to determine the correct dose of AZT for young children. Of a total of 908 pediatric AIDS cases, 78 percent have acquired HIV infection from a mother with HIV infection or at high risk for acquisition of HIV, and the number of cases in children is expected to increase over the next several years. AZT therapy may be effective in altering the course of the disease and decreasing the high mortality in these children. It is also possible that early intervention with AZT may prevent the establishment of HIV contracted before, during, or just after birth.


Condition Intervention Phase
HIV Infections
Drug: Zidovudine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Multicenter Phase I Trial To Evaluate the Safety and Pharmacokinetics of Intravenous and Oral Zidovudine in Infants With Perinatal Human Immunodeficiency Virus (HIV) Exposure

Resource links provided by NLM:


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

Estimated Enrollment: 18
Detailed Description:

Of a total of 908 pediatric AIDS cases, 78 percent have acquired HIV infection from a mother with HIV infection or at high risk for acquisition of HIV, and the number of cases in children is expected to increase over the next several years. AZT therapy may be effective in altering the course of the disease and decreasing the high mortality in these children. It is also possible that early intervention with AZT may prevent the establishment of HIV contracted before, during, or just after birth.

The children entered in this study receive oral and IV AZT. The first 6 children receive 2 IV doses and 2 oral doses over a 2-week period, then 4 weeks of continuous oral dosing (4 doses per day). The remaining 12 children receive

1 IV dose and 1 oral dose followed by 6 weeks of oral AZT (4 doses per day) and a second IV dose at the end of the study. Each child is under the care of a specialist in pediatrics and has a physical examination and laboratory tests before starting AZT and 6 times while taking AZT to make sure the drug is not having a toxic effect on the child. A single cerebrospinal fluid (CSF) sample is taken from the last 12 children entering the study, so that the level of the AZT reaching the brain can be measured. The child returns to the hospital or clinic 4 weeks after the end of therapy to make sure that there are no delayed toxic effects.

  Eligibility

Ages Eligible for Study:   up to 3 Months
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria

Infant gestation period must have been = or > 36 weeks and birthweight must = or > 2000 grams. Active infection must not be present at the time of entry into the study although an HIV culture or P24 serum antigen determination must be obtained prior to study entry. The child must have a life expectancy greater than 3 months. Parents or guardian must be available to give informed consent.

Prior Medication:

Allowed on a case-by-case basis:

  • Some essential supportive therapies including antibiotics.

Exclusion Criteria

Co-existing Condition:

Patients with the following conditions or symptoms are excluded:

  • Any of the following laboratory findings within 2 weeks of study entry.
  • A total bilirubin > 2 times age-adjusted upper limit of normal.
  • Liver transaminase values > 3 x upper limit of normal.
  • Serum creatinine > 1.5 x upper limit of normal.
  • Total granulocyte count < 1500 cells/mm3.
  • Hemoglobin < 10 g/dl or hemoglobinopathy.
  • A urine toxicology screen positive for any drug or chemical.
  • Infants must not have hemoglobinopathy or active infection at entry.

Prior Medication:

Excluded within 2 months of study entry:

  • Antiretroviral agents.
  • Excluded within 4 weeks of study entry:
  • Immunomodulating agents including steroids, interferon, isoprinosine, and interleukin.
  • Immunoglobulin.
  • Excluded within 2 weeks of study entry:
  • Any other experimental therapy, drugs which cause prolonged neutropenia or significant nephrotoxicity, or rifampin / rifampin derivatives.
  • Some essential supportive therapies including antibiotics may have infrequent or transient effects. These drugs will be considered on a case-by-case basis.

Prior Treatment:

Excluded within 2 weeks of study entry:

  • Red blood cells or whole blood transfusion.
  • Excluded within 4 weeks of study entry:
  • Lymphocyte transfusions for immune reconstitution.

Infants may not be entered into the study during the first 2 weeks of life if their mother received methadone therapy during the last trimester of her pregnancy or used any known illicit drug. A maternal urine toxicology screen may be optionally performed prior to entry of the child, and children whose mothers have a screen which is positive for any drugs or chemicals may not be enrolled within 2 weeks of the positive screen.

  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: NCT00001007

Locations
United States, Alabama
Univ of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
Stanford Univ School of Medicine
Stanford, California, United States, 94305
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
Johns Hopkins Hosp - Pediatric
Baltimore, Maryland, United States, 212874933
United States, Massachusetts
Boston Med Ctr
Boston, Massachusetts, United States, 02118
United States, North Carolina
Duke Univ Med Ctr
Durham, North Carolina, United States, 277103499
Sponsors and Collaborators
Glaxo Wellcome
Investigators
Study Chair: Modlin J
  More Information

Additional Information:
Publications:
ClinicalTrials.gov Identifier: NCT00001007     History of Changes
Other Study ID Numbers: ACTG 049, FDA 9D
Study First Received: November 2, 1999
Last Updated: July 11, 2008
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Pregnancy
Pregnancy Complications, Infectious
Infant, Newborn, Diseases
Infusions, Intravenous
Drug Evaluation
Administration, Oral
Acquired Immunodeficiency Syndrome
Zidovudine

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus 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 September 22, 2014