A Phase III Randomized, Double-Blind, Controlled Study of the Use of Anti-HIV Immune Serum Globulin (HIVIG) for the Prevention of Maternal-Fetal HIV Transmission in Pregnant Women and Newborns Receiving Zidovudine (AZT)

NCT ID: NCT00000751

Last Updated: 2008-09-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1600 participants

Study Classification

INTERVENTIONAL

Study Completion Date

2007-08-31

Brief Summary

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To evaluate the effect of anti-HIV immune serum globulin (HIVIG) versus immune globulin (IVIG) administered during pregnancy and to the newborn, in combination with zidovudine (AZT) administered intrapartum and to the newborn, on incidence of HIV infection in infants born to HIV-infected women who received AZT during pregnancy for medical indications.

Vertical transmission of HIV from mother to child may occur before, during, or after parturition (via breast-feeding). It is believed that therapy administered both during pregnancy and intrapartum may help prevent vertical transmission. Additionally, adjunctive short-term antiretroviral therapy for the newborn, following the intensive viral exposure presumed to occur at birth, may be necessary.

Detailed Description

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Vertical transmission of HIV from mother to child may occur before, during, or after parturition (via breast-feeding). It is believed that therapy administered both during pregnancy and intrapartum may help prevent vertical transmission. Additionally, adjunctive short-term antiretroviral therapy for the newborn, following the intensive viral exposure presumed to occur at birth, may be necessary.

Pregnant women who are currently receiving AZT are randomized at 20-30 weeks of gestation to begin receiving either HIVIG or IVIG every 28 days up to delivery. Within 12 hours after birth, the infant receives an infusion of matching study drug. During labor, all women receive an intravenous loading dose of AZT administered over 1 hour, followed by continuous infusion during the intrapartum period until the umbilical cord is clamped. All infants receive AZT syrup every 6 hours, beginning as soon as oral fluids are tolerated but within 8-12 hours after birth and continuing for 6 weeks. Women are followed until 26 weeks postpartum. Infants are followed at weeks 1, 2, 4, and then every 4 weeks through week 24, every 12 weeks through week 60, at week 78 (18 months), and at week 104 (24 months).

Conditions

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HIV Infections Pregnancy

Keywords

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Pregnancy Pregnancy Complications, Infectious Drug Therapy, Combination Acquired Immunodeficiency Syndrome AIDS-Related Complex Zidovudine Immunoglobulins, Intravenous Immunization, Passive

Study Design

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Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Interventions

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Anti-HIV Immune Serum Globulin (Human)

Intervention Type DRUG

Globulin, Immune

Intervention Type DRUG

Zidovudine

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Concurrent Medication:

Allowed:

* Women - Medications as required for obstetrical management of HIV infection (e.g., acyclovir, ketoconazole, isoniazid, antibiotics, or other antiretroviral therapy if intolerant or failing on AZT), unless specifically excluded.
* Infants - Drug treatment for signs of drug withdrawal (phenobarbital, chlorpromazine, tincture of opium, paregoric or Valium).
* Infants - Medications as indicated for management of an HIV-exposed infant (e.g., hepatitis B vaccine, syphilis treatment, Pneumocystis carinii pneumonia prophylaxis).

Patients must have:

* Documented HIV infection.
* Been receiving AZT during current pregnancy for medical indications.
* Gestational age between 20 and 30 weeks.
* Intention to carry pregnancy to term.
* Available venous access (placement of central line or Hickman catheter not indicated for study purposes).
* Willingness to be followed by a participating site for study duration.

NOTE:

* Father of fetus (if available after a reasonable attempt to contact him) must also provide informed consent.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

* Illness associated with excessive protein loss, e.g., severe proteinuria (protein \>= 4 g protein in a 24-hour urine collection).

Patients with the following prior conditions are excluded:

* Evidence of pre-existing fetal anomalies (e.g., anencephaly, renal agenesis, or Potter's syndrome) that may result in a high probability that the fetus-infant would not survive to the end of the study period.
* Chorionic villus sampling (CVS) or percutaneous umbilical blood sampling (PUBS) occurring in this pregnancy prior to study entry.
* Illness associated with excessive protein loss, e.g., chronic diarrhea with no documented weight gain in a 3-month period during pregnancy.
* Pre-existing conditions such as hypogammaglobulinemia or immune thrombocytopenia that are felt to require IVIG therapy.

Prior Medication:

Excluded:

* Receipt of anti-HIV vaccines or passive immunotherapy with HIVIG or IVIG during this pregnancy prior to study entry.
* Receipt of antiretroviral agents other than AZT during this pregnancy prior to study entry (e.g., rCD4, CD4-IgG, d4T, ddC, ddI).
Minimum Eligible Age

13 Years

Maximum Eligible Age

60 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role lead

Principal Investigators

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ER Stiehm

Role: STUDY_CHAIR

J Lambert

Role: STUDY_CHAIR

Locations

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UCSD Med Ctr / Pediatrics / Clinical Sciences

La Jolla, California, United States

Site Status

Los Angeles County - USC Med Ctr

Los Angeles, California, United States

Site Status

UCLA Med Ctr / Pediatric

Los Angeles, California, United States

Site Status

Harbor - UCLA Med Ctr / UCLA School of Medicine

Los Angeles, California, United States

Site Status

San Francisco Gen Hosp

San Francisco, California, United States

Site Status

UCSF / Moffitt Hosp - Pediatric

San Francisco, California, United States

Site Status

Denver Gen Hosp

Denver, Colorado, United States

Site Status

Children's Hosp of Denver

Denver, Colorado, United States

Site Status

Univ of Connecticut / Farmington

Farmington, Connecticut, United States

Site Status

Children's Hosp of Washington DC

Washington D.C., District of Columbia, United States

Site Status

Washington Hosp Ctr

Washington D.C., District of Columbia, United States

Site Status

Howard Univ Hosp

Washington D.C., District of Columbia, United States

Site Status

Univ of Florida Health Science Ctr / Pediatrics

Jacksonville, Florida, United States

Site Status

Univ of Miami (Pediatric)

Miami, Florida, United States

Site Status

Univ of Illinois College of Medicine / Pediatrics

Chicago, Illinois, United States

Site Status

Tulane Univ / Charity Hosp of New Orleans

New Orleans, Louisiana, United States

Site Status

Univ Hosp

New Orleans, Louisiana, United States

Site Status

Univ of Maryland at Baltimore / Univ Med Ctr

Baltimore, Maryland, United States

Site Status

Johns Hopkins Hosp - Pediatric

Baltimore, Maryland, United States

Site Status

Children's Hosp of Boston

Boston, Massachusetts, United States

Site Status

Brigham and Women's Hosp

Boston, Massachusetts, United States

Site Status

Boston City Hosp / Pediatrics

Boston, Massachusetts, United States

Site Status

Baystate Med Ctr of Springfield

Springfield, Massachusetts, United States

Site Status

Univ of Massachusetts Med School

Worcester, Massachusetts, United States

Site Status

Children's Hosp of Michigan

Detroit, Michigan, United States

Site Status

Univ of Medicine & Dentistry of New Jersey / Univ Hosp

Newark, New Jersey, United States

Site Status

Children's Hosp at Albany Med Ctr

Albany, New York, United States

Site Status

Bellevue Hosp / New York Univ Med Ctr

New York, New York, United States

Site Status

Mount Sinai Med Ctr / Pediatrics

New York, New York, United States

Site Status

Columbia Presbyterian Med Ctr

New York, New York, United States

Site Status

State Univ of New York at Stony Brook

Stony Brook, New York, United States

Site Status

SUNY Health Sciences Ctr at Syracuse / Pediatrics

Syracuse, New York, United States

Site Status

Bronx Lebanon Hosp Ctr

The Bronx, New York, United States

Site Status

Univ of North Carolina at Chapel Hill / Duke Univ Med Ctr

Durham, North Carolina, United States

Site Status

Case Western Reserve Univ - Pediatric

Cleveland, Ohio, United States

Site Status

Children's Hosp of Philadelphia

Philadelphia, Pennsylvania, United States

Site Status

Hosp of the Univ of Pennsylvania

Philadelphia, Pennsylvania, United States

Site Status

Thomas Jefferson Univ Hosp

Philadelphia, Pennsylvania, United States

Site Status

Saint Christopher's Hosp for Children

Philadelphia, Pennsylvania, United States

Site Status

Temple Univ School of Medicine

Philadelphia, Pennsylvania, United States

Site Status

Med Univ of South Carolina

Charleston, South Carolina, United States

Site Status

Regional Med Ctr at Memphis

Memphis, Tennessee, United States

Site Status

Methodist Hosp Central

Memphis, Tennessee, United States

Site Status

Saint Jude Children's Research Hosp of Memphis

Memphis, Tennessee, United States

Site Status

Children's Med Ctr of Dallas

Dallas, Texas, United States

Site Status

Hermann Hosp / Univ Texas Health Science Ctr

Houston, Texas, United States

Site Status

Texas Children's Hosp / Baylor Univ

Houston, Texas, United States

Site Status

Children's Hospital & Medical Center / Seattle ACTU

Seattle, Washington, United States

Site Status

Ramon Ruiz Arnau Univ Hosp / Pediatrics

Bayamón, , Puerto Rico

Site Status

Univ of Puerto Rico / Univ Children's Hosp AIDS

San Juan, , Puerto Rico

Site Status

San Juan City Hosp

San Juan, , Puerto Rico

Site Status

Countries

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United States Puerto Rico

References

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Mofenson LM. Interventions to reduce perinatal transmission. Natl Conf Women HIV. 1997 May 4-7:125 (abstract no 2011)

Reference Type BACKGROUND

McKinney RE Jr. Ongoing and future trials of antiretroviral therapy in the pediatric AIDS clinical trials group (PACTG). Conf Retroviruses Opportunistic Infect. 1996 Jan 28-Feb 1;3rd:173

Reference Type BACKGROUND

Lambert J, Fletcher C, Mofenson L, Stiehm ER, Moye J, Meyer W, Nemo G, Mathieson B, Hirsch G. Pharmacokinetics (PK) of hyperimmune HIV immunoglobulin (HIVIG) in HIV+ pregnant females & newborns. Natl Conf Hum Retroviruses Relat Infect (2nd). 1995 Jan 29-Feb 2:148

Reference Type BACKGROUND

Lambert JS, Watts DH, Mofenson L, Stiehm ER, Harris DR, Bethel J, Whitehouse J, Jimenez E, Gandia J, Scott G, O'Sullivan MJ, Kovacs A, Stek A, Shearer WT, Hammill H, van Dyke R, Maupin R, Silio M, Fowler MG. Risk factors for preterm birth, low birth weight, and intrauterine growth retardation in infants born to HIV-infected pregnant women receiving zidovudine. Pediatric AIDS Clinical Trials Group 185 Team. AIDS. 2000 Jul 7;14(10):1389-99. doi: 10.1097/00002030-200007070-00012.

Reference Type BACKGROUND
PMID: 10930154 (View on PubMed)

Mofenson LM, Lambert JS, Stiehm ER, Bethel J, Meyer WA 3rd, Whitehouse J, Moye J Jr, Reichelderfer P, Harris DR, Fowler MG, Mathieson BJ, Nemo GJ. Risk factors for perinatal transmission of human immunodeficiency virus type 1 in women treated with zidovudine. Pediatric AIDS Clinical Trials Group Study 185 Team. N Engl J Med. 1999 Aug 5;341(6):385-93. doi: 10.1056/NEJM199908053410601.

Reference Type BACKGROUND
PMID: 10432323 (View on PubMed)

Lambert JS, Mofenson LM, Fletcher CV, Moye J Jr, Stiehm ER, Meyer WA 3rd, Nemo GJ, Mathieson BJ, Hirsch G, Sapan CV, Cummins LM, Jimenez E, O'Neill E, Kovacs A, Stek A. Safety and pharmacokinetics of hyperimmune anti-human immunodeficiency virus (HIV) immunoglobulin administered to HIV-infected pregnant women and their newborns. Pediatric AIDS Clinical Trials Group Protocol 185 Pharmacokinetic Study Group. J Infect Dis. 1997 Feb;175(2):283-91. doi: 10.1093/infdis/175.2.283.

Reference Type BACKGROUND
PMID: 9203648 (View on PubMed)

Lambert JS, Moye J, Sapan C, Mofenson L, Fletcher C, Whitehouse J, Fowler MG, Nemo G, Stiehm ER. Demonstration of feasibility and preliminary safety and pharmaco-kinetics in a phase III study of hyperimmune HIV intravenous immunoglobulin (HIV-IG) to prevent maternal-fetal HIV transmission. Int Conf AIDS. 1996 Jul 7-12;11(2):84 (abstract no WeB3163)

Reference Type BACKGROUND

Frenkel LM. Therapeutic issues pertaining to HIV-1 infected pregnant women in developed countries. 39th Intersci Conf Antimicrob Agents Chemother. 1999 Sept 26-29

Reference Type BACKGROUND

Watts DH, Lambert J, Stiehm ER, Harris DR, Bethel J, Mofenson L, Meyer WA 3rd, Mathieson B, Fowler MG, Nemo G; PACTG 185 Study Team. Progression of HIV disease among women following delivery. J Acquir Immune Defic Syndr. 2003 Aug 15;33(5):585-93. doi: 10.1097/00126334-200308150-00006.

Reference Type BACKGROUND
PMID: 12902802 (View on PubMed)

Lambert JS. HIV vaccines in infants and children. Paediatr Drugs. 2005;7(5):267-76. doi: 10.2165/00148581-200507050-00001.

Reference Type RESULT
PMID: 16220994 (View on PubMed)

Other Identifiers

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ACTG 185

Identifier Type: -

Identifier Source: org_study_id