Clinical 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)

This study is no longer recruiting patients.

Sponsors and Collaborators: National Institute of Child Health and Human Development (NICHD)
National Institute of Allergy and Infectious Diseases (NIAID)
Information provided by: National Institute of Allergy and Infectious Diseases (NIAID)

Purpose

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.

Condition Treatment or Intervention Phase
HIV Infections
Pregnancy
 Drug: Anti-HIV Immune Serum Globulin (Human)
 Drug: Globulin, Immune
 Drug: Zidovudine
Phase III

MedlinePlus related topics:  AIDS

Study Type: Interventional
Study Design: Treatment, Parallel Assignment, Safety Study

Further Study Details: 

Expected Total Enrollment:  1600

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).

Eligibility

Ages Eligible for Study:  13 Years   -   60 Years,  Genders Eligible for Study:  Female

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).

Location Information


California
      UCSF / Moffitt Hosp - Pediatric, San Francisco,  California,  941430105,  United States

      UCSD Med Ctr / Pediatrics / Clinical Sciences, La Jolla,  California,  920930672,  United States

      San Francisco Gen Hosp, San Francisco,  California,  94110,  United States

      Harbor - UCLA Med Ctr / UCLA School of Medicine, Los Angeles,  California,  905022004,  United States

      UCLA Med Ctr / Pediatric, Los Angeles,  California,  900951752,  United States

      Los Angeles County - USC Med Ctr, Los Angeles,  California,  90033,  United States

Colorado
      Children's Hosp of Denver, Denver,  Colorado,  802181088,  United States

      Denver Gen Hosp, Denver,  Colorado,  802044507,  United States

Connecticut
      Univ of Connecticut / Farmington, Farmington,  Connecticut,  06032,  United States

District of Columbia
      Washington Hosp Ctr, Washington,  District of Columbia,  200102931,  United States

      Howard Univ Hosp, Washington,  District of Columbia,  20060,  United States

      Children's Hosp of Washington DC, Washington,  District of Columbia,  200102916,  United States

Florida
      Univ of Miami (Pediatric), Miami,  Florida,  33161,  United States

      Univ of Florida Health Science Ctr / Pediatrics, Jacksonville,  Florida,  32209,  United States

Illinois
      Univ of Illinois College of Medicine / Pediatrics, Chicago,  Illinois,  60612,  United States

Louisiana
      Tulane Univ / Charity Hosp of New Orleans, New Orleans,  Louisiana,  701122699,  United States

      Univ Hosp, New Orleans,  Louisiana,  70112,  United States

Maryland
      Univ of Maryland at Baltimore / Univ Med Ctr, Baltimore,  Maryland,  21201,  United States

      Johns Hopkins Hosp - Pediatric, Baltimore,  Maryland,  212874933,  United States

Massachusetts
      Children's Hosp of Boston, Boston,  Massachusetts,  021155724,  United States

      Boston City Hosp / Pediatrics, Boston,  Massachusetts,  02118,  United States

      Brigham and Women's Hosp, Boston,  Massachusetts,  02115,  United States

      Baystate Med Ctr of Springfield, Springfield,  Massachusetts,  01199,  United States

      Univ of Massachusetts Med School, Worcester,  Massachusetts,  016550001,  United States

Michigan
      Children's Hosp of Michigan, Detroit,  Michigan,  48201,  United States

New Jersey
      Univ of Medicine & Dentistry of New Jersey / Univ Hosp, Newark,  New Jersey,  071032714,  United States

New York
      Bellevue Hosp / New York Univ Med Ctr, New York,  New York,  10016,  United States

      Columbia Presbyterian Med Ctr, New York,  New York,  10032,  United States

      Mount Sinai Med Ctr / Pediatrics, New York,  New York,  10029,  United States

      Children's Hosp at Albany Med Ctr, Albany,  New York,  12208,  United States

      SUNY Health Sciences Ctr at Syracuse / Pediatrics, Syracuse,  New York,  13210,  United States

      Bronx Lebanon Hosp Ctr, Bronx,  New York,  10457,  United States

      State Univ of New York at Stony Brook, Stony Brook,  New York,  117948111,  United States

North Carolina
      Univ of North Carolina at Chapel Hill / Duke Univ Med Ctr, Durham,  North Carolina,  27710,  United States

Ohio
      Case Western Reserve Univ - Pediatric, Cleveland,  Ohio,  44106,  United States

Pennsylvania
      Temple Univ School of Medicine, Philadelphia,  Pennsylvania,  191341095,  United States

      Children's Hosp of Philadelphia, Philadelphia,  Pennsylvania,  191044318,  United States

      Hosp of the Univ of Pennsylvania, Philadelphia,  Pennsylvania,  19104,  United States

      Thomas Jefferson Univ Hosp, Philadelphia,  Pennsylvania,  191075098,  United States

      Saint Christopher's Hosp for Children, Philadelphia,  Pennsylvania,  191341095,  United States

South Carolina
      Med Univ of South Carolina, Charleston,  South Carolina,  294253312,  United States

Tennessee
      Methodist Hosp Central, Memphis,  Tennessee,  381052794,  United States

      Saint Jude Children's Research Hosp of Memphis, Memphis,  Tennessee,  381052794,  United States

      Regional Med Ctr at Memphis, Memphis,  Tennessee,  38103,  United States

Texas
      Children's Med Ctr of Dallas, Dallas,  Texas,  75235,  United States

      Hermann Hosp / Univ Texas Health Science Ctr, Houston,  Texas,  77030,  United States

      Texas Children's Hosp / Baylor Univ, Houston,  Texas,  77030,  United States

Washington
      Children's Hospital & Medical Center / Seattle ACTU, Seattle,  Washington,  981050371,  United States

Puerto Rico
      San Juan City Hosp, San Juan,  009367344,  Puerto Rico

      Univ of Puerto Rico / Univ Children's Hosp AIDS, San Juan,  009365067,  Puerto Rico

      Ramon Ruiz Arnau Univ Hosp / Pediatrics, Bayamon,  00956,  Puerto Rico

Study chairs or principal investigators

ER Stiehm,  Study Chair
J Lambert,  Study Chair

More Information

Click here for more information about zidovudine

Click here for more information about Globulin, Immune

Publications

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

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

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

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

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.

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.

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.

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)

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.

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

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.

Study ID Numbers:  ACTG 185
Record last reviewed:  August 2004
Last Updated:  October 13, 2004
Record first received:  November 2, 1999
ClinicalTrials.gov Identifier:  NCT00000751
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08


Source: ClinicalTrials.gov
Cache Date: April 9, 2005

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