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

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00000960
• Collaborator: Glaxo Wellcome (Industry)
• Enrollment: 1,496
• Locations: 62
• Patients Per Site: 24.1

Study Details

Study Description

Brief 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.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections; Pregnancy	Drug: Zidovudine	Phase 3

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.

Study Design

• Study Type: Interventional
• 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
• Actual Study Completion Date: Jun 1, 1994

Outcome Measures

Primary Outcome Measures

Eligibility Criteria

Criteria

• Ages Eligible for Study: 1 Day to 60 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

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

Locations

	Site	City	State	Country	Postal Code
1	Univ of Alabama at Birmingham Schl of Med / Pediatrics	Birmingham	Alabama	United States	35294
2	Univ of Alabama at Birmingham	Birmingham	Alabama	United States	35294
3	UCSD Med Ctr / Pediatrics / Clinical Sciences	La Jolla	California	United States	920930672
4	Los Angeles County - USC Med Ctr	Los Angeles	California	United States	90033
5	UCLA Med Ctr / Pediatric	Los Angeles	California	United States	900951752
6	Harbor - UCLA Med Ctr / UCLA School of Medicine	Los Angeles	California	United States	905022004
7	San Francisco Gen Hosp	San Francisco	California	United States	94110
8	Children's Hosp of Denver	Denver	Colorado	United States	802181088
9	Univ of Connecticut / Farmington	Farmington	Connecticut	United States	06032
10	Univ of Connecticut Health Ctr	Farmington	Connecticut	United States	06032
11	Howard Univ Hosp	Washington	District of Columbia	United States	20060
12	Univ of Miami (Pediatric)	Miami	Florida	United States	33161
13	Northwestern Univ Med School	Chicago	Illinois	United States	60611
14	Cook County Hosp	Chicago	Illinois	United States	60612
15	Univ of Illinois College of Medicine / Pediatrics	Chicago	Illinois	United States	60612
16	Chicago Children's Memorial Hosp	Chicago	Illinois	United States	606143394
17	Univ of Chicago Children's Hosp	Chicago	Illinois	United States	606371470
18	Tulane Univ / Charity Hosp of New Orleans	New Orleans	Louisiana	United States	701122699
19	Univ of Maryland at Baltimore / Univ Med Ctr	Baltimore	Maryland	United States	21201
20	Johns Hopkins Hosp - Pediatric	Baltimore	Maryland	United States	212874933
21	Johns Hopkins Hosp	Baltimore	Maryland	United States	21287
22	Children's Hosp of Boston	Boston	Massachusetts	United States	021155724
23	Boston City Hosp / Pediatrics	Boston	Massachusetts	United States	02118
24	Beth Israel Deaconess Med Ctr	Boston	Massachusetts	United States	02215
25	Baystate Med Ctr of Springfield	Springfield	Massachusetts	United States	01199
26	Univ of Massachusetts Med Ctr	Worcester	Massachusetts	United States	01655
27	Children's Hosp of Michigan	Detroit	Michigan	United States	48201
28	UMDNJ - New Jersy Med School	Newark	New Jersey	United States	071032714
29	Univ of Medicine & Dentistry of New Jersey / Univ Hosp	Newark	New Jersey	United States	071032714
30	Children's Hosp of New Jersey / UMDNJ - New Jersey Med Schl	Newark	New Jersey	United States	071072198
31	Children's Hosp at Albany Med Ctr	Albany	New York	United States	12208
32	Bronx Lebanon Hosp Ctr	Bronx	New York	United States	10457
33	Albert Einstein College of Medicine	Bronx	New York	United States	10461
34	SUNY - Brooklyn	Brooklyn	New York	United States	11203
35	SUNY / Health Sciences Ctr at Brooklyn / Pediatrics	Brooklyn	New York	United States	11203
36	Beth Israel Med Ctr / Pediatrics	New York	New York	United States	10003
37	Bellevue Hosp / New York Univ Med Ctr	New York	New York	United States	10016
38	Cornell Univ Med College	New York	New York	United States	10021
39	Mount Sinai Med Ctr / Pediatrics	New York	New York	United States	10029
40	Columbia Presbyterian Med Ctr	New York	New York	United States	10032
41	Univ of Rochester Medical Center	Rochester	New York	United States	14642
42	State Univ of New York at Stony Brook	Stony Brook	New York	United States	117948111
43	SUNY Health Sciences Ctr at Syracuse / Pediatrics	Syracuse	New York	United States	13210
44	Westchester Hosp	Valhalla	New York	United States	10595
45	Univ of North Carolina	Chapel Hill	North Carolina	United States	275997215
46	Carolinas Med Ctr	Charlotte	North Carolina	United States	28203
47	Duke Univ Med Ctr	Durham	North Carolina	United States	277103499
48	Univ of Cincinnati	Cincinnati	Ohio	United States	452670405
49	Children's Hosp of Philadelphia	Philadelphia	Pennsylvania	United States	191044318
50	Hosp of the Univ of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
51	Thomas Jefferson Univ Hosp	Philadelphia	Pennsylvania	United States	191075098
52	Rhode Island Hosp / Brown Univ	Providence	Rhode Island	United States	02903
53	Med Univ of South Carolina	Charleston	South Carolina	United States	294253312
54	Saint Jude Children's Research Hosp of Memphis	Memphis	Tennessee	United States	381052794
55	Children's Med Ctr of Dallas	Dallas	Texas	United States	75235
56	Lyndon Baines Johnson Gen Hosp	Houston	Texas	United States	77030
57	Texas Children's Hosp / Baylor Univ	Houston	Texas	United States	77030
58	Children's Hosp of Seattle	Seattle	Washington	United States	98105
59	Ramon Ruiz Arnau Univ Hosp / Pediatrics	Bayamon		Puerto Rico	00956
60	Univ of Puerto Rico / Univ Children's Hosp AIDS	San Juan		Puerto Rico	009365067
61	UPR Children's Hosp / UPR School of Medicine	San Juan		Puerto Rico	009365067
62	San Juan City Hosp	San Juan		Puerto Rico	009367344

Sponsors and Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID)
• Glaxo Wellcome

Investigators

• Study Chair: E Connor,
• Study Chair: R Sperling,

Study Documents (Full-Text)

None provided.

More Information

Publications

• 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.
• 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.
• 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.
• 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.
• Newell ML, Gray G, Bryson YJ. Prevention of mother-to-child transmission of HIV-1 infection. AIDS. 1997;11 Suppl A:S165-72. Review.
• Rouzioux C. Prevention of maternal HIV transmission. Practical guidelines. Drugs. 1995;49 Suppl 1:17-24; discussion 38-40. Review.
• 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.
• 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.
• 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.
• 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.

• Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
• ClinicalTrials.gov Identifier: NCT00000960
• Other Study ID Numbers: ACTG 076; 11050
• First Posted: Aug 31, 2001
• Last Update Posted: Oct 29, 2021
• Last Verified: Oct 1, 2021

• 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; Zidovudine

Study Results

No Results Posted as of Oct 29, 2021