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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)

Primary Purpose

HIV Infections, Pregnancy

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Anti-HIV Immune Serum Globulin (Human)
Globulin, Immune
Zidovudine
Sponsored by
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for HIV Infections focused on measuring Pregnancy, Pregnancy Complications, Infectious, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Zidovudine, Immunoglobulins, Intravenous, Immunization, Passive

Eligibility Criteria

13 Years - 60 Years (Child, Adult)FemaleDoes not accept healthy volunteers

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).

Sites / Locations

  • UCSD Med Ctr / Pediatrics / Clinical Sciences
  • Los Angeles County - USC Med Ctr
  • UCLA Med Ctr / Pediatric
  • Harbor - UCLA Med Ctr / UCLA School of Medicine
  • San Francisco Gen Hosp
  • UCSF / Moffitt Hosp - Pediatric
  • Denver Gen Hosp
  • Children's Hosp of Denver
  • Univ of Connecticut / Farmington
  • Children's Hosp of Washington DC
  • Washington Hosp Ctr
  • Howard Univ Hosp
  • Univ of Florida Health Science Ctr / Pediatrics
  • Univ of Miami (Pediatric)
  • Univ of Illinois College of Medicine / Pediatrics
  • Tulane Univ / Charity Hosp of New Orleans
  • Univ Hosp
  • Univ of Maryland at Baltimore / Univ Med Ctr
  • Johns Hopkins Hosp - Pediatric
  • Children's Hosp of Boston
  • Brigham and Women's Hosp
  • Boston City Hosp / Pediatrics
  • Baystate Med Ctr of Springfield
  • Univ of Massachusetts Med School
  • Children's Hosp of Michigan
  • Univ of Medicine & Dentistry of New Jersey / Univ Hosp
  • Children's Hosp at Albany Med Ctr
  • Bronx Lebanon Hosp Ctr
  • Bellevue Hosp / New York Univ Med Ctr
  • Mount Sinai Med Ctr / Pediatrics
  • Columbia Presbyterian Med Ctr
  • State Univ of New York at Stony Brook
  • SUNY Health Sciences Ctr at Syracuse / Pediatrics
  • Univ of North Carolina at Chapel Hill / Duke Univ Med Ctr
  • Case Western Reserve Univ - Pediatric
  • Children's Hosp of Philadelphia
  • Hosp of the Univ of Pennsylvania
  • Thomas Jefferson Univ Hosp
  • Saint Christopher's Hosp for Children
  • Temple Univ School of Medicine
  • Med Univ of South Carolina
  • Regional Med Ctr at Memphis
  • Methodist Hosp Central
  • Saint Jude Children's Research Hosp of Memphis
  • Children's Med Ctr of Dallas
  • Hermann Hosp / Univ Texas Health Science Ctr
  • Texas Children's Hosp / Baylor Univ
  • Children's Hospital & Medical Center / Seattle ACTU
  • Ramon Ruiz Arnau Univ Hosp / Pediatrics
  • Univ of Puerto Rico / Univ Children's Hosp AIDS
  • San Juan City Hosp

Outcomes

Primary Outcome Measures

Secondary Outcome Measures

Full Information

First Posted
November 2, 1999
Last Updated
September 26, 2008
Sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)
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1. Study Identification

Unique Protocol Identification Number
NCT00000751
Brief Title
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)
Official Title
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)
Study Type
Interventional

2. Study Status

Record Verification Date
May 2006
Overall Recruitment Status
Completed
Study Start Date
undefined (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
August 2007 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Collaborators
National Institute of Allergy and Infectious Diseases (NIAID)

4. Oversight

5. Study Description

Brief Summary
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
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, Pregnancy
Keywords
Pregnancy, Pregnancy Complications, Infectious, Drug Therapy, Combination, Acquired Immunodeficiency Syndrome, AIDS-Related Complex, Zidovudine, Immunoglobulins, Intravenous, Immunization, Passive

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Enrollment
1600 (false)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
Anti-HIV Immune Serum Globulin (Human)
Intervention Type
Drug
Intervention Name(s)
Globulin, Immune
Intervention Type
Drug
Intervention Name(s)
Zidovudine

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
13 Years
Maximum Age & Unit of Time
60 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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).
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
ER Stiehm
Official's Role
Study Chair
First Name & Middle Initial & Last Name & Degree
J Lambert
Official's Role
Study Chair
Facility Information:
Facility Name
UCSD Med Ctr / Pediatrics / Clinical Sciences
City
La Jolla
State/Province
California
ZIP/Postal Code
920930672
Country
United States
Facility Name
Los Angeles County - USC Med Ctr
City
Los Angeles
State/Province
California
ZIP/Postal Code
90033
Country
United States
Facility Name
UCLA Med Ctr / Pediatric
City
Los Angeles
State/Province
California
ZIP/Postal Code
900951752
Country
United States
Facility Name
Harbor - UCLA Med Ctr / UCLA School of Medicine
City
Los Angeles
State/Province
California
ZIP/Postal Code
905022004
Country
United States
Facility Name
San Francisco Gen Hosp
City
San Francisco
State/Province
California
ZIP/Postal Code
94110
Country
United States
Facility Name
UCSF / Moffitt Hosp - Pediatric
City
San Francisco
State/Province
California
ZIP/Postal Code
941430105
Country
United States
Facility Name
Denver Gen Hosp
City
Denver
State/Province
Colorado
ZIP/Postal Code
802044507
Country
United States
Facility Name
Children's Hosp of Denver
City
Denver
State/Province
Colorado
ZIP/Postal Code
802181088
Country
United States
Facility Name
Univ of Connecticut / Farmington
City
Farmington
State/Province
Connecticut
ZIP/Postal Code
06032
Country
United States
Facility Name
Children's Hosp of Washington DC
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
200102916
Country
United States
Facility Name
Washington Hosp Ctr
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
200102931
Country
United States
Facility Name
Howard Univ Hosp
City
Washington
State/Province
District of Columbia
ZIP/Postal Code
20060
Country
United States
Facility Name
Univ of Florida Health Science Ctr / Pediatrics
City
Jacksonville
State/Province
Florida
ZIP/Postal Code
32209
Country
United States
Facility Name
Univ of Miami (Pediatric)
City
Miami
State/Province
Florida
ZIP/Postal Code
33161
Country
United States
Facility Name
Univ of Illinois College of Medicine / Pediatrics
City
Chicago
State/Province
Illinois
ZIP/Postal Code
60612
Country
United States
Facility Name
Tulane Univ / Charity Hosp of New Orleans
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
701122699
Country
United States
Facility Name
Univ Hosp
City
New Orleans
State/Province
Louisiana
ZIP/Postal Code
70112
Country
United States
Facility Name
Univ of Maryland at Baltimore / Univ Med Ctr
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21201
Country
United States
Facility Name
Johns Hopkins Hosp - Pediatric
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
212874933
Country
United States
Facility Name
Children's Hosp of Boston
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
021155724
Country
United States
Facility Name
Brigham and Women's Hosp
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02115
Country
United States
Facility Name
Boston City Hosp / Pediatrics
City
Boston
State/Province
Massachusetts
ZIP/Postal Code
02118
Country
United States
Facility Name
Baystate Med Ctr of Springfield
City
Springfield
State/Province
Massachusetts
ZIP/Postal Code
01199
Country
United States
Facility Name
Univ of Massachusetts Med School
City
Worcester
State/Province
Massachusetts
ZIP/Postal Code
016550001
Country
United States
Facility Name
Children's Hosp of Michigan
City
Detroit
State/Province
Michigan
ZIP/Postal Code
48201
Country
United States
Facility Name
Univ of Medicine & Dentistry of New Jersey / Univ Hosp
City
Newark
State/Province
New Jersey
ZIP/Postal Code
071032714
Country
United States
Facility Name
Children's Hosp at Albany Med Ctr
City
Albany
State/Province
New York
ZIP/Postal Code
12208
Country
United States
Facility Name
Bronx Lebanon Hosp Ctr
City
Bronx
State/Province
New York
ZIP/Postal Code
10457
Country
United States
Facility Name
Bellevue Hosp / New York Univ Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10016
Country
United States
Facility Name
Mount Sinai Med Ctr / Pediatrics
City
New York
State/Province
New York
ZIP/Postal Code
10029
Country
United States
Facility Name
Columbia Presbyterian Med Ctr
City
New York
State/Province
New York
ZIP/Postal Code
10032
Country
United States
Facility Name
State Univ of New York at Stony Brook
City
Stony Brook
State/Province
New York
ZIP/Postal Code
117948111
Country
United States
Facility Name
SUNY Health Sciences Ctr at Syracuse / Pediatrics
City
Syracuse
State/Province
New York
ZIP/Postal Code
13210
Country
United States
Facility Name
Univ of North Carolina at Chapel Hill / Duke Univ Med Ctr
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27710
Country
United States
Facility Name
Case Western Reserve Univ - Pediatric
City
Cleveland
State/Province
Ohio
ZIP/Postal Code
44106
Country
United States
Facility Name
Children's Hosp of Philadelphia
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
191044318
Country
United States
Facility Name
Hosp of the Univ of Pennsylvania
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
19104
Country
United States
Facility Name
Thomas Jefferson Univ Hosp
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
191075098
Country
United States
Facility Name
Saint Christopher's Hosp for Children
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
191341095
Country
United States
Facility Name
Temple Univ School of Medicine
City
Philadelphia
State/Province
Pennsylvania
ZIP/Postal Code
191341095
Country
United States
Facility Name
Med Univ of South Carolina
City
Charleston
State/Province
South Carolina
ZIP/Postal Code
294253312
Country
United States
Facility Name
Regional Med Ctr at Memphis
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
38103
Country
United States
Facility Name
Methodist Hosp Central
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
381052794
Country
United States
Facility Name
Saint Jude Children's Research Hosp of Memphis
City
Memphis
State/Province
Tennessee
ZIP/Postal Code
381052794
Country
United States
Facility Name
Children's Med Ctr of Dallas
City
Dallas
State/Province
Texas
ZIP/Postal Code
75235
Country
United States
Facility Name
Hermann Hosp / Univ Texas Health Science Ctr
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Texas Children's Hosp / Baylor Univ
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Facility Name
Children's Hospital & Medical Center / Seattle ACTU
City
Seattle
State/Province
Washington
ZIP/Postal Code
981050371
Country
United States
Facility Name
Ramon Ruiz Arnau Univ Hosp / Pediatrics
City
Bayamon
ZIP/Postal Code
00956
Country
Puerto Rico
Facility Name
Univ of Puerto Rico / Univ Children's Hosp AIDS
City
San Juan
ZIP/Postal Code
009365067
Country
Puerto Rico
Facility Name
San Juan City Hosp
City
San Juan
ZIP/Postal Code
009367344
Country
Puerto Rico

12. IPD Sharing Statement

Citations:
Citation
Mofenson LM. Interventions to reduce perinatal transmission. Natl Conf Women HIV. 1997 May 4-7:125 (abstract no 2011)
Results Reference
background
Citation
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
Results Reference
background
Citation
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
Results Reference
background
PubMed Identifier
10930154
Citation
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.
Results Reference
background
PubMed Identifier
10432323
Citation
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.
Results Reference
background
PubMed Identifier
9203648
Citation
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.
Results Reference
background
Citation
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)
Results Reference
background
Citation
Frenkel LM. Therapeutic issues pertaining to HIV-1 infected pregnant women in developed countries. 39th Intersci Conf Antimicrob Agents Chemother. 1999 Sept 26-29
Results Reference
background
PubMed Identifier
12902802
Citation
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.
Results Reference
background
PubMed Identifier
16220994
Citation
Lambert JS. HIV vaccines in infants and children. Paediatr Drugs. 2005;7(5):267-76. doi: 10.2165/00148581-200507050-00001.
Results Reference
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Learn more about this trial

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)

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