Clinical trial NCT00000920: Fortovase (Saquinavir) Given With Low-Dose Ritonavir, Zidovudine, and Lamivudine to HIV-Positive Pregnant Women During and After Pregnancy and to Their Newborns
Official title: A Phase I Trial of the Safety and Pharmacokinetics of Fortovase (Saquinavir-SGC) Co-Administered With Low Dose (Ritonavir) RTV, ZDV and 3TC in HIV Seropositive Pregnant Women During Gestation and Postpartum, and in Their Infant's Post-Maternal Dosing
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Pregnancy
Keywords: Pregnancy
Drug Therapy, Combination
Zidovudine
Pregnancy Complications
Ritonavir
Lamivudine
Saquinavir
Anti-HIV Agents
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2001-08-31
Enrollment: 24
Sex: ALL
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: The purpose of this study is to see if it is safe to give saquinavir-SGC (SQV) combined with low-dose ritonavir (RTV) plus zidovudine (ZDV) and lamivudine (3TC) to HIV-positive pregnant women and to see if it is safe to give 3TC and ZDV to their newborns. Another purpose is to see what levels of SQV, low-dose RTV, ZDV, and 3TC are found in mothers and what levels of ZDV and 3TC are seen in newborns. Another purpose of this study is to see whether SQV passes from mother to newborn and if it passes at a level that is safe for the newborn.

Although ZDV has been able to reduce the rate of transmission of HIV from mother to child, it may be possible to reduce it further by using a combination of anti-HIV drugs. This study adds SQV (a protease inhibitor \[PI\]) with RTV (another PI) and 3TC (a reverse transcriptase inhibitor) to the mother's ZDV regimen.

Detailed description: Although administration of ZDV to mother-infant pairs has dramatically reduced perinatal HIV infection, the goal is to reduce it further to less than 2%. In order to achieve this, combination strategies need to be developed for 2 purposes: 1) to reduce the perinatal transmission rate to goal levels; and 2) to provide other combination therapies for HIV-infected mothers whose virus has become resistant to ZDV, who have a very high viral load, or who have previously transmitted HIV while on ZDV. This study adds 3TC (another reverse transcriptase inhibitor) and SQV (a protease inhibitor \[PI\]) \[AS PER AMENDMENT 08/15/00: with low-dose RTV (another PI)\] to the mother's ZDV regimen.

During the antepartum period, mothers receive SQV with \[AS PER AMENDMENT 08/15/00: low-dose RTV plus\] ZDV and 3TC. At onset of active labor, mothers receive loading doses of each of the study drugs, then receive study drugs for 12 weeks postpartum on the same schedule as during the antenatal period. Within 12 hours of delivery, infants begin receiving 3TC and ZDV and continue until 6 weeks of age. Mothers are followed until 12 weeks postpartum and babies are followed until 6 months of age. \[AS PER AMENDMENT 02/09/99: For maternal dosing, 1 Combivir tablet (containing 3TC and ZDV) may be administered in place of the individual agents 3TC and ZDV. Patients who prematurely discontinue study treatment should continue to be followed for the duration of the study.\]

Eligibility criteria: Inclusion Criteria

Patients may be eligible for this study if they:

* Are HIV-positive.
* Are 14 to 32 weeks pregnant.
* Are at least 13 years old (need consent of parent or guardian if under 18).

Exclusion Criteria

Patients may not be eligible for this study if they:

* Cannot take ZDV, 3TC, or higher doses of RTV. Women who are able to tolerate low doses of RTV may be eligible.
* Are pregnant with more than 1 baby. (This study has been changed so that a patient pregnant with more than 1 baby is not eligible.)
* Have pregnancy complications or have medical problems that put pregnancy at risk.
* Have an active opportunistic (HIV-related) infection and/or serious bacterial infection at study entry.
* Have chronic diarrhea.
* Abuse alcohol or drugs.
* Do not have access to a participating clinic or are not willing to be followed at the same clinic for the duration of the study.
* Have received certain antiretroviral (anti-HIV) drugs or are taking certain medications. (This study has been changed to increase enrollment. The eligibility criterion in earlier versions was more restrictive, and has been changed to include women receiving SQV \[with or without RTV\], 3TC, and ZDV for longer than 3 weeks if their pre-entry viral load is 400 copies/ml or less OR if they have a significant reduction in viral load within 90 days of the pre-entry visit.)
* Plan to breast-feed.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Los Angeles County - USC Med Ctr
state: California
city: Denver
country: United States
facility: Univ of Colorado Health Sciences Ctr
state: Colorado
city: Washington
country: United States
facility: Howard Univ Hosp
state: District of Columbia
city: Miami
country: United States
facility: Univ of Miami / Jackson Memorial Hosp
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: 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: New York
country: United States
facility: Columbia Presbyterian Med Ctr
state: New York
city: Durham
country: United States
facility: Duke Univ Med Ctr
state: North Carolina
city: Charleston
country: United States
facility: Med Univ of South Carolina
state: South Carolina
city: Seattle
country: United States
facility: Children's Hospital & Medical Center / Seattle ACTU
state: Washington
city: San Juan
country: Puerto Rico
facility: Univ of Puerto Rico / Univ Children's Hosp AIDS
Study officials:
name: Carmen Zorrilla
role: STUDY_CHAIR
name: Arlene Bardeguez
role: STUDY_CHAIR
name: Jane Pitt
role: STUDY_CHAIR
name: Russell Van Dyke
role: STUDY_CHAIR
References:
citation: Acosta EP, Zorrilla C, Van Dyke R, Bardeguez A, Smith E, Hughes M, Huang S, Pitt J, Watts H, Mofenson L; Pediatric AIDS Clinical Trials Group 386 Protocol Team. Pharmacokinetics of saquinavir-SGC in HIV-infected pregnant women. HIV Clin Trials. 2001 Nov-Dec;2(6):460-5. doi: 10.1310/PUY3-5JWL-FX2B-98VU.