The Safety and Effectiveness of Zidovudine in HIV-Infected Pregnant Women and Their Infants

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:
NCT00000960
First received: November 2, 1999
Last updated: March 15, 2012
Last verified: March 2012
  Purpose

To determine whether the rate of HIV transmission from mother to infant can be reduced by continuous oral zidovudine (AZT) treatment to HIV infected pregnant women, intravenous AZT during childbirth, and oral AZT treatment of the newborn infant from birth to six weeks of age. The study is also designed to evaluate the safety of AZT for both the pregnant woman and the newborn infant.

No method exists to prevent transmission of HIV from an infected mother to her newborn infant. Giving an antiviral agent (such as AZT) to the mother and to the newborn could in theory decrease the risk of infection to the newborn by reducing the exposure of the fetus to maternal virus, or by preventive treatment of the fetus before exposure.


Condition Intervention Phase
HIV Infections
Pregnancy
Drug: Zidovudine
Phase 3

Study Type: Interventional
Study Design: Primary Purpose: Treatment
Official Title: A Phase III Randomized Placebo-Controlled Trial to Evaluate the Efficacy, Safety and Tolerance of Oral Zidovudine (AZT) in Pregnant HIV Infected Women and Their Infants

Resource links provided by NLM:


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

Estimated Enrollment: 1496
Study Completion Date: June 1994
Detailed Description:

No method exists to prevent transmission of HIV from an infected mother to her newborn infant. Giving an antiviral agent (such as AZT) to the mother and to the newborn could in theory decrease the risk of infection to the newborn by reducing the exposure of the fetus to maternal virus, or by preventive treatment of the fetus before exposure.

Patients are enrolled during their pregnancy, between 14 and 34 weeks of gestation. They are chosen by random selection to receive AZT or placebo. Treatment continues until labor at which time they begin to receive continuous intravenous study drug. Study drug treatment is discontinued after the umbilical cord is clamped. AZT is then offered all women as per labeled indications for 6 weeks postpartum, while appropriate medical followup is being arranged. Mothers who develop an AIDS defining illness or whose CD4+ cell counts decrease to less than 200 cells/mm3 during pregnancy are offered open-label drug at that time. The mother is followed by her primary obstetrician at an AIDS Clinical Trials Unit (ACTU) or subunit facility. The mother may deliver at the ACTU or a non-ACTU site. Treatment of the infant is started in the newborn nursery and continues on an outpatient basis. Infants receive the same study treatment as the mother for 6 weeks, and are monitored to week 78.

  Eligibility

Ages Eligible for Study:   up to 60 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Concurrent Medication:

Allowed for infants:

  • Treatment for signs of drug withdrawal (e.g., phenobarbital, chlorpromazine, tincture of opium, paregoric, or Valium).
  • Treatment for nonserious conditions (e.g., syphilis treatment, hepatitis B vaccine).
  • All essential supportive treatment for conditions that are nonlife threatening as deemed by the on-site pediatrician.
  • Acetaminophen.
  • Standard immunizations.
  • Allowed for women:
  • All medications/treatments as required for normal OB care of HIV+ women, except as noted under exclusions.
  • Pneumocystis prophylaxis as indicated.
  • Topical steroids. Parenteral and oral steroids for 6 or fewer days.

Concurrent Treatment:

Allowed for pregnant woman:

Blood transfusion for anemia (hemoglobin less than 7 g/dl).

Allowed for infant:

- Blood transfusions for anemia except if attributed to study drug.

-

Patients must:

  • Have HIV infection.
  • Intend to carry pregnancy to term.
  • Be willing to be followed by a participating ACTG center for duration of the study.
  • Be able to provide informed consent (if available, father of the fetus must also provide informed consent).
  • Infants may enroll simultaneously in other pediatric protocols after completing the initial 6 weeks of study treatment.
  • Inclusion age for women is 13 years old or more or IRB local age of consent.
  • Inclusion age for infants is 0 to 20 months.

Exclusion Criteria

Co-existing Condition:

Infants with the following conditions or symptoms are excluded:

  • Requiring treatment for hyperbilirubinemia (except phototherapy).

Concurrent Medication:

Excluded:

  • Infants:
  • Antiretroviral drugs or vaccines.
  • Excluded during current pregnancy:
  • Zidovudine (AZT).
  • Other antiretroviral agents (e.g., rCD4, CD4-IgG, d4T, didanosine (ddI), dideoxycytidine (ddC)), passive immunotherapy (e.g., HIVIG), anti-HIV vaccines, cytolytic chemotherapeutic agents.
  • Corticosteroids for equal to or more than 7 days.

Patients with the following are excluded:

  • Evidence of preexisting fetal anomalies that may (1) result in a high probability that the fetus/infant will not survive to the end of the study period (e.g., anencephaly, renal agenesis, or Potter's syndrome); or (2) increase the fetal tissue concentration of zidovudine (AZT) or its metabolites to a toxic level (e.g., neural tube or ventral wall defects).
  • Baseline sonogram completed within 28 days prior to randomization that demonstrates 2nd trimester findings of anencephaly or oligohydramnios, or 3rd trimester findings of unexplained polyhydramnios, fetal hydrops, ascites or other evidence of preexisting in-utero anemia.
  • History of intolerance to AZT dose of 500 or less mg/day prior to this pregnancy that resulted in discontinuation of treatment for more than 4 weeks.
  • Recipient of AZT during current pregnancy for any indication or meet criteria for AZT as defined by this protocol (CD4+ cell counts less than 200 cells/mm3 or AIDS).
  • Infants not having parent/guardian available to give informed consent if necessary.

Prior Treatment:

Excluded during current pregnancy:

  • Radiation therapy.
  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: NCT00000960

  Hide Study Locations
Locations
United States, Alabama
Univ of Alabama at Birmingham Schl of Med / Pediatrics
Birmingham, Alabama, United States, 35294
Univ of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
UCSD Med Ctr / Pediatrics / Clinical Sciences
La Jolla, California, United States, 920930672
Harbor - UCLA Med Ctr / UCLA School of Medicine
Los Angeles, California, United States, 905022004
UCLA Med Ctr / Pediatric
Los Angeles, California, United States, 900951752
Los Angeles County - USC Med Ctr
Los Angeles, California, United States, 90033
San Francisco Gen Hosp
San Francisco, California, United States, 94110
United States, Colorado
Children's Hosp of Denver
Denver, Colorado, United States, 802181088
United States, Connecticut
Univ of Connecticut Health Ctr
Farmington, Connecticut, United States, 06032
Univ of Connecticut / Farmington
Farmington, Connecticut, United States, 06032
United States, District of Columbia
Howard Univ Hosp
Washington, District of Columbia, United States, 20060
United States, Florida
Univ of Miami (Pediatric)
Miami, Florida, United States, 33161
United States, Illinois
Chicago Children's Memorial Hosp
Chicago, Illinois, United States, 606143394
Cook County Hosp
Chicago, Illinois, United States, 60612
Northwestern Univ Med School
Chicago, Illinois, United States, 60611
Univ of Illinois College of Medicine / Pediatrics
Chicago, Illinois, United States, 60612
Univ of Chicago Children's Hosp
Chicago, Illinois, United States, 606371470
United States, Louisiana
Tulane Univ / Charity Hosp of New Orleans
New Orleans, Louisiana, United States, 701122699
United States, Maryland
Johns Hopkins Hosp
Baltimore, Maryland, United States, 21287
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
Beth Israel Deaconess Med Ctr
Boston, Massachusetts, United States, 02215
Children's Hosp of Boston
Boston, Massachusetts, United States, 021155724
Boston City Hosp / Pediatrics
Boston, Massachusetts, United States, 02118
Baystate Med Ctr of Springfield
Springfield, Massachusetts, United States, 01199
Univ of Massachusetts Med Ctr
Worcester, Massachusetts, United States, 01655
United States, Michigan
Children's Hosp of Michigan
Detroit, Michigan, United States, 48201
United States, New Jersey
Univ of Medicine & Dentistry of New Jersey / Univ Hosp
Newark, New Jersey, United States, 071032714
Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl
Newark, New Jersey, United States, 071072198
UMDNJ - New Jersy Med School
Newark, New Jersey, United States, 071032714
United States, New York
Children's Hosp at Albany Med Ctr
Albany, New York, United States, 12208
Bronx Lebanon Hosp Ctr
Bronx, New York, United States, 10457
Albert Einstein College of Medicine
Bronx, New York, United States, 10461
SUNY - Brooklyn
Brooklyn, New York, United States, 11203
SUNY / Health Sciences Ctr at Brooklyn / Pediatrics
Brooklyn, New York, United States, 11203
Columbia Presbyterian Med Ctr
New York, New York, United States, 10032
Beth Israel Med Ctr / Pediatrics
New York, New York, United States, 10003
Bellevue Hosp / New York Univ Med Ctr
New York, New York, United States, 10016
Cornell Univ Med College
New York, New York, United States, 10021
Mount Sinai Med Ctr / Pediatrics
New York, New York, United States, 10029
Univ of Rochester Medical Center
Rochester, New York, United States, 14642
State Univ of New York at Stony Brook
Stony Brook, New York, United States, 117948111
SUNY Health Sciences Ctr at Syracuse / Pediatrics
Syracuse, New York, United States, 13210
Westchester Hosp
Valhalla, New York, United States, 10595
United States, North Carolina
Univ of North Carolina
Chapel Hill, North Carolina, United States, 275997215
Carolinas Med Ctr
Charlotte, North Carolina, United States, 28203
Duke Univ Med Ctr
Durham, North Carolina, United States, 277103499
United States, Ohio
Univ of Cincinnati
Cincinnati, Ohio, United States, 452670405
United States, Pennsylvania
Children's Hosp of Philadelphia
Philadelphia, Pennsylvania, United States, 191044318
Hosp of the Univ of Pennsylvania
Philadelphia, Pennsylvania, United States, 19104
Thomas Jefferson Univ Hosp
Philadelphia, Pennsylvania, United States, 191075098
United States, Rhode Island
Rhode Island Hosp / Brown Univ
Providence, Rhode Island, United States, 02903
United States, South Carolina
Med Univ of South Carolina
Charleston, South Carolina, United States, 294253312
United States, Tennessee
Saint Jude Children's Research Hosp of Memphis
Memphis, Tennessee, United States, 381052794
United States, Texas
Children's Med Ctr of Dallas
Dallas, Texas, United States, 75235
Lyndon Baines Johnson Gen Hosp
Houston, Texas, United States, 77030
Texas Children's Hosp / Baylor Univ
Houston, Texas, United States, 77030
United States, Washington
Children's Hosp of Seattle
Seattle, Washington, United States, 98105
Puerto Rico
Ramon Ruiz Arnau Univ Hosp / Pediatrics
Bayamon, Puerto Rico, 00956
San Juan City Hosp
San Juan, Puerto Rico, 009367344
UPR Children's Hosp / UPR School of Medicine
San Juan, Puerto Rico, 009365067
Univ of Puerto Rico / Univ Children's Hosp AIDS
San Juan, Puerto Rico, 009365067
Sponsors and Collaborators
Glaxo Wellcome
Investigators
Study Chair: E Connor
Study Chair: R Sperling
  More Information

Additional Information:
Publications:

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000960     History of Changes
Other Study ID Numbers: ACTG 076, 11050
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):
Pregnancy
Pregnancy Complications, Infectious
Prenatal Exposure Delayed Effects
Administration, Oral
AIDS-Related Complex
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 August 27, 2014