Clinical trial NCT00000751: 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
Overall status: COMPLETED
Phase: PHASE3
Conditions: HIV Infections
Pregnancy
Keywords: Pregnancy
Pregnancy Complications, Infectious
Drug Therapy, Combination
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Zidovudine
Immunoglobulins, Intravenous
Immunization, Passive
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: National Institute of Allergy and Infectious Diseases (NIAID)
First posted: 2001-08-31
Enrollment: 1600
Sex: FEMALE
Minimum age (years): 13
Maximum age (years): 60
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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).

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: La Jolla
country: United States
facility: UCSD Med Ctr / Pediatrics / Clinical Sciences
state: California
city: Los Angeles
country: United States
facility: Los Angeles County - USC Med Ctr
state: California
city: Los Angeles
country: United States
facility: UCLA Med Ctr / Pediatric
state: California
city: Los Angeles
country: United States
facility: Harbor - UCLA Med Ctr / UCLA School of Medicine
state: California
city: San Francisco
country: United States
facility: San Francisco Gen Hosp
state: California
city: San Francisco
country: United States
facility: UCSF / Moffitt Hosp - Pediatric
state: California
city: Denver
country: United States
facility: Denver Gen Hosp
state: Colorado
city: Denver
country: United States
facility: Children's Hosp of Denver
state: Colorado
city: Farmington
country: United States
facility: Univ of Connecticut / Farmington
state: Connecticut
city: Washington
country: United States
facility: Children's Hosp of Washington DC
state: District of Columbia
city: Washington
country: United States
facility: Washington Hosp Ctr
state: District of Columbia
city: Washington
country: United States
facility: Howard Univ Hosp
state: District of Columbia
city: Jacksonville
country: United States
facility: Univ of Florida Health Science Ctr / Pediatrics
state: Florida
city: Miami
country: United States
facility: Univ of Miami (Pediatric)
state: Florida
city: Chicago
country: United States
facility: Univ of Illinois College of Medicine / Pediatrics
state: Illinois
city: New Orleans
country: United States
facility: Tulane Univ / Charity Hosp of New Orleans
state: Louisiana
city: New Orleans
country: United States
facility: Univ Hosp
state: Louisiana
city: Baltimore
country: United States
facility: Univ of Maryland at Baltimore / Univ Med Ctr
state: Maryland
city: Baltimore
country: United States
facility: Johns Hopkins Hosp - Pediatric
state: Maryland
city: Boston
country: United States
facility: Children's Hosp of Boston
state: Massachusetts
city: Boston
country: United States
facility: Brigham and Women's Hosp
state: Massachusetts
city: Boston
country: United States
facility: Boston City Hosp / Pediatrics
state: Massachusetts
city: Springfield
country: United States
facility: Baystate Med Ctr of Springfield
state: Massachusetts
city: Worcester
country: United States
facility: Univ of Massachusetts Med School
state: Massachusetts
city: Detroit
country: United States
facility: Children's Hosp of Michigan
state: Michigan
city: Newark
country: United States
facility: Univ of Medicine & Dentistry of New Jersey / Univ Hosp
state: New Jersey
city: Albany
country: United States
facility: Children's Hosp at Albany Med Ctr
state: New York
city: Bronx
country: United States
facility: Bronx Lebanon Hosp Ctr
state: New York
city: New York
country: United States
facility: Bellevue Hosp / New York Univ Med Ctr
state: New York
city: New York
country: United States
facility: Mount Sinai Med Ctr / Pediatrics
state: New York
city: New York
country: United States
facility: Columbia Presbyterian Med Ctr
state: New York
city: Stony Brook
country: United States
facility: State Univ of New York at Stony Brook
state: New York
city: Syracuse
country: United States
facility: SUNY Health Sciences Ctr at Syracuse / Pediatrics
state: New York
city: Durham
country: United States
facility: Univ of North Carolina at Chapel Hill / Duke Univ Med Ctr
state: North Carolina
city: Cleveland
country: United States
facility: Case Western Reserve Univ - Pediatric
state: Ohio
city: Philadelphia
country: United States
facility: Children's Hosp of Philadelphia
state: Pennsylvania
city: Philadelphia
country: United States
facility: Hosp of the Univ of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Thomas Jefferson Univ Hosp
state: Pennsylvania
city: Philadelphia
country: United States
facility: Saint Christopher's Hosp for Children
state: Pennsylvania
city: Philadelphia
country: United States
facility: Temple Univ School of Medicine
state: Pennsylvania
city: Charleston
country: United States
facility: Med Univ of South Carolina
state: South Carolina
city: Memphis
country: United States
facility: Regional Med Ctr at Memphis
state: Tennessee
city: Memphis
country: United States
facility: Methodist Hosp Central
state: Tennessee
city: Memphis
country: United States
facility: Saint Jude Children's Research Hosp of Memphis
state: Tennessee
city: Dallas
country: United States
facility: Children's Med Ctr of Dallas
state: Texas
city: Houston
country: United States
facility: Hermann Hosp / Univ Texas Health Science Ctr
state: Texas
city: Houston
country: United States
facility: Texas Children's Hosp / Baylor Univ
state: Texas
city: Seattle
country: United States
facility: Children's Hospital & Medical Center / Seattle ACTU
state: Washington
city: Bayamon
country: Puerto Rico
facility: Ramon Ruiz Arnau Univ Hosp / Pediatrics
city: San Juan
country: Puerto Rico
facility: Univ of Puerto Rico / Univ Children's Hosp AIDS
city: San Juan
country: Puerto Rico
facility: San Juan City Hosp
Study officials:
name: ER Stiehm
role: STUDY_CHAIR
name: J Lambert
role: STUDY_CHAIR
References:
citation: Mofenson LM. Interventions to reduce perinatal transmission. Natl Conf Women HIV. 1997 May 4-7:125 (abstract no 2011)
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
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
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.
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.
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.
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)
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
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.
citation: Lambert JS. HIV vaccines in infants and children. Paediatr Drugs. 2005;7(5):267-76. doi: 10.2165/00148581-200507050-00001.