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)

HIV Infections Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00000751
• Other study ID #: ACTG 185
• Status: Completed
• Phase: Phase 3
• First received: November 2, 1999
• Last updated: September 26, 2008
• Est. completion date: August 2007

Study information

• Verified date: May 2006
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1600
• Est. completion date: August 2007
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 13 Years to 60 Years

Eligibility

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).

Study Design

Endpoint Classification: Safety Study, Intervention Model: Parallel Assignment, Primary Purpose: Treatment

Related Conditions & MeSH terms

• HIV Infections
• Pregnancy

Intervention

Drug:
• Anti-HIV Immune Serum Globulin (Human)

• Globulin, Immune

• 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
United States	Children's Hosp at Albany Med Ctr	Albany	New York
United States	Johns Hopkins Hosp - Pediatric	Baltimore	Maryland
United States	Univ of Maryland at Baltimore / Univ Med Ctr	Baltimore	Maryland
United States	Boston City Hosp / Pediatrics	Boston	Massachusetts
United States	Brigham and Women's Hosp	Boston	Massachusetts
United States	Children's Hosp of Boston	Boston	Massachusetts
United States	Bronx Lebanon Hosp Ctr	Bronx	New York
United States	Med Univ of South Carolina	Charleston	South Carolina
United States	Univ of Illinois College of Medicine / Pediatrics	Chicago	Illinois
United States	Case Western Reserve Univ - Pediatric	Cleveland	Ohio
United States	Children's Med Ctr of Dallas	Dallas	Texas
United States	Children's Hosp of Denver	Denver	Colorado
United States	Denver Gen Hosp	Denver	Colorado
United States	Children's Hosp of Michigan	Detroit	Michigan
United States	Univ of North Carolina at Chapel Hill / Duke Univ Med Ctr	Durham	North Carolina
United States	Univ of Connecticut / Farmington	Farmington	Connecticut
United States	Hermann Hosp / Univ Texas Health Science Ctr	Houston	Texas
United States	Texas Children's Hosp / Baylor Univ	Houston	Texas
United States	Univ of Florida Health Science Ctr / Pediatrics	Jacksonville	Florida
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	Methodist Hosp Central	Memphis	Tennessee
United States	Regional Med Ctr at Memphis	Memphis	Tennessee
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	Univ Hosp	New Orleans	Louisiana
United States	Bellevue Hosp / New York Univ Med Ctr	New York	New York
United States	Columbia Presbyterian Med Ctr	New York	New York
United States	Mount Sinai Med Ctr / Pediatrics	New York	New York
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	Saint Christopher's Hosp for Children	Philadelphia	Pennsylvania
United States	Temple Univ School of Medicine	Philadelphia	Pennsylvania
United States	Thomas Jefferson Univ Hosp	Philadelphia	Pennsylvania
United States	San Francisco Gen Hosp	San Francisco	California
United States	UCSF / Moffitt Hosp - Pediatric	San Francisco	California
United States	Children's Hospital & Medical Center / Seattle ACTU	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	Children's Hosp of Washington DC	Washington	District of Columbia
United States	Howard Univ Hosp	Washington	District of Columbia
United States	Washington Hosp Ctr	Washington	District of Columbia
United States	Univ of Massachusetts Med School	Worcester	Massachusetts

Sponsors (2)

Lead Sponsor	Collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)	National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Puerto Rico, 

References & Publications (10)

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

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

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. — View 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)

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. — View Citation

Lambert JS. HIV vaccines in infants and children. Paediatr Drugs. 2005;7(5):267-76. Review. — View 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

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. — View Citation

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

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. — View Citation

External Links

•   Click here for more information about immune globulin
•   Click here for more information about zidovudine
•   Click here for more information on HIV preventive vaccines