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

HIV Infections Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000960
• Other study ID #: ACTG 076
• Secondary ID: 11050
• Status: Completed
• Phase: Phase 3
• Est. completion date: June 1994

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1496
• Est. completion date: June 1994
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 60 Years

Eligibility

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.

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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.

Related Conditions & MeSH terms

• HIV Infections
• Pregnancy

Intervention

Drug:
• Zidovudine

Locations

Country	Name	City	State
Puerto Rico	Ramon Ruiz Arnau Univ Hosp / Pediatrics	Bayamon
Puerto Rico	San Juan City Hosp	San Juan
Puerto Rico	Univ of Puerto Rico / Univ Children's Hosp AIDS	San Juan
Puerto Rico	UPR Children's Hosp / UPR School of Medicine	San Juan
United States	Children's Hosp at Albany Med Ctr	Albany	New York
United States	Johns Hopkins Hosp	Baltimore	Maryland
United States	Johns Hopkins Hosp - Pediatric	Baltimore	Maryland
United States	Univ of Maryland at Baltimore / Univ Med Ctr	Baltimore	Maryland
United States	Univ of Alabama at Birmingham	Birmingham	Alabama
United States	Univ of Alabama at Birmingham Schl of Med / Pediatrics	Birmingham	Alabama
United States	Beth Israel Deaconess Med Ctr	Boston	Massachusetts
United States	Boston City Hosp / Pediatrics	Boston	Massachusetts
United States	Children's Hosp of Boston	Boston	Massachusetts
United States	Albert Einstein College of Medicine	Bronx	New York
United States	Bronx Lebanon Hosp Ctr	Bronx	New York
United States	SUNY - Brooklyn	Brooklyn	New York
United States	SUNY / Health Sciences Ctr at Brooklyn / Pediatrics	Brooklyn	New York
United States	Univ of North Carolina	Chapel Hill	North Carolina
United States	Med Univ of South Carolina	Charleston	South Carolina
United States	Carolinas Med Ctr	Charlotte	North Carolina
United States	Chicago Children's Memorial Hosp	Chicago	Illinois
United States	Cook County Hosp	Chicago	Illinois
United States	Northwestern Univ Med School	Chicago	Illinois
United States	Univ of Chicago Children's Hosp	Chicago	Illinois
United States	Univ of Illinois College of Medicine / Pediatrics	Chicago	Illinois
United States	Univ of Cincinnati	Cincinnati	Ohio
United States	Children's Med Ctr of Dallas	Dallas	Texas
United States	Children's Hosp of Denver	Denver	Colorado
United States	Children's Hosp of Michigan	Detroit	Michigan
United States	Duke Univ Med Ctr	Durham	North Carolina
United States	Univ of Connecticut / Farmington	Farmington	Connecticut
United States	Univ of Connecticut Health Ctr	Farmington	Connecticut
United States	Lyndon Baines Johnson Gen Hosp	Houston	Texas
United States	Texas Children's Hosp / Baylor Univ	Houston	Texas
United States	UCSD Med Ctr / Pediatrics / Clinical Sciences	La Jolla	California
United States	Harbor - UCLA Med Ctr / UCLA School of Medicine	Los Angeles	California
United States	Los Angeles County - USC Med Ctr	Los Angeles	California
United States	UCLA Med Ctr / Pediatric	Los Angeles	California
United States	Saint Jude Children's Research Hosp of Memphis	Memphis	Tennessee
United States	Univ of Miami (Pediatric)	Miami	Florida
United States	Tulane Univ / Charity Hosp of New Orleans	New Orleans	Louisiana
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Beth Israel Med Ctr / Pediatrics	New York	New York
United States	Columbia Presbyterian Med Ctr	New York	New York
United States	Cornell Univ Med College	New York	New York
United States	Mount Sinai Med Ctr / Pediatrics	New York	New York
United States	Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl	Newark	New Jersey
United States	UMDNJ - New Jersy Med School	Newark	New Jersey
United States	Univ of Medicine & Dentistry of New Jersey / Univ Hosp	Newark	New Jersey
United States	Children's Hosp of Philadelphia	Philadelphia	Pennsylvania
United States	Hosp of the Univ of Pennsylvania	Philadelphia	Pennsylvania
United States	Thomas Jefferson Univ Hosp	Philadelphia	Pennsylvania
United States	Rhode Island Hosp / Brown Univ	Providence	Rhode Island
United States	Univ of Rochester Medical Center	Rochester	New York
United States	San Francisco Gen Hosp	San Francisco	California
United States	Children's Hosp of Seattle	Seattle	Washington
United States	Baystate Med Ctr of Springfield	Springfield	Massachusetts
United States	State Univ of New York at Stony Brook	Stony Brook	New York
United States	SUNY Health Sciences Ctr at Syracuse / Pediatrics	Syracuse	New York
United States	Westchester Hosp	Valhalla	New York
United States	Howard Univ Hosp	Washington	District of Columbia
United States	Univ of Massachusetts Med Ctr	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)	Glaxo Wellcome

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (11)

Connor EM, Sperling RS, Gelber R, Kiselev P, Scott G, O'Sullivan MJ, VanDyke R, Bey M, Shearer W, Jacobson RL, et al. Reduction of maternal-infant transmission of human immunodeficiency virus type 1 with zidovudine treatment. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med. 1994 Nov 3;331(18):1173-80. — View Citation

Culnane M, Fowler M, Lee SS, McSherry G, Brady M, O'Donnell K, Mofenson L, Gortmaker SL, Shapiro DE, Scott G, Jimenez E, Moore EC, Diaz C, Flynn PM, Cunningham B, Oleske J. Lack of long-term effects of in utero exposure to zidovudine among uninfected children born to HIV-infected women. Pediatric AIDS Clinical Trials Group Protocol 219/076 Teams. JAMA. 1999 Jan 13;281(2):151-7. — View Citation

Dickover RE, Garratty EM, Herman SA, Sim MS, Plaeger S, Boyer PJ, Keller M, Deveikis A, Stiehm ER, Bryson YJ. Identification of levels of maternal HIV-1 RNA associated with risk of perinatal transmission. Effect of maternal zidovudine treatment on viral load. JAMA. 1996 Feb 28;275(8):599-605. — View Citation

Edathodu J, Halim MM, Dahham MB, Alrajhi AA. Mother-to-child transmission of HIV: experience at a referral hospital in Saudi Arabia. Ann Saudi Med. 2010 Jan-Feb;30(1):15-7. doi: 10.4103/0256-4947.59367. — View Citation

Frenkel LM, Cowles MK, Shapiro DE, Melvin AJ, Watts DH, McLellan C, Mohan K, Murante B, Burchett S, Bryson YJ, O'Sullivan MJ, Mitchell C, Landers D. Analysis of the maternal components of the AIDS clinical trial group 076 zidovudine regimen in the prevention of mother-to-infant transmission of human immunodeficiency virus type 1. J Infect Dis. 1997 Apr;175(4):971-4. — View Citation

Newell ML, Gray G, Bryson YJ. Prevention of mother-to-child transmission of HIV-1 infection. AIDS. 1997;11 Suppl A:S165-72. Review. — View Citation

Rouzioux C. Prevention of maternal HIV transmission. Practical guidelines. Drugs. 1995;49 Suppl 1:17-24; discussion 38-40. Review. — View Citation

Shearer WT, Quinn TC, LaRussa P, Lew JF, Mofenson L, Almy S, Rich K, Handelsman E, Diaz C, Pagano M, Smeriglio V, Kalish LA. Viral load and disease progression in infants infected with human immunodeficiency virus type 1. Women and Infants Transmission Study Group. N Engl J Med. 1997 May 8;336(19):1337-42. — View Citation

Sperling RS, Shapiro DE, Coombs RW, Todd JA, Herman SA, McSherry GD, O'Sullivan MJ, Van Dyke RB, Jimenez E, Rouzioux C, Flynn PM, Sullivan JL. Maternal viral load, zidovudine treatment, and the risk of transmission of human immunodeficiency virus type 1 from mother to infant. Pediatric AIDS Clinical Trials Group Protocol 076 Study Group. N Engl J Med. 1996 Nov 28;335(22):1621-9. — View Citation

Sperling RS, Shapiro DE, McSherry GD, Britto P, Cunningham BE, Culnane M, Coombs RW, Scott G, Van Dyke RB, Shearer WT, Jimenez E, Diaz C, Harrison DD, Delfraissy JF. Safety of the maternal-infant zidovudine regimen utilized in the Pediatric AIDS Clinical Trial Group 076 Study. AIDS. 1998 Oct 1;12(14):1805-13. — View Citation

Wiznia AA, Crane M, Lambert G, Sansary J, Harris A, Solomon L. Zidovudine use to reduce perinatal HIV type 1 transmission in an urban medical center. JAMA. 1996 May 15;275(19):1504-6. — View Citation

* Note: There are 11 references in all — Click here to view all references