Clinical trial NCT00000839: A Phase I Trial to Evaluate Didanosine (ddI) in HIV-Infected Pregnant Women
Official title: A Phase I Trial to Evaluate Didanosine (ddI) in HIV-Infected Pregnant Women
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Pregnancy
Keywords: Pregnancy Trimester, Third
Pregnancy
Pregnancy Complications, Infectious
Didanosine
Acquired Immunodeficiency Syndrome
AIDS-Related Complex
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Bristol-Myers Squibb
First posted: 2001-08-31
Enrollment: 12
Sex: FEMALE
Minimum age (years): 13
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Primary purpose: TREATMENT

Brief summary: To assess the pharmacokinetics, safety, and toxicity of intravenous and oral didanosine (ddI) administration in third trimester pregnant women who are HIV positive but are either intolerant or resistant to zidovudine (AZT). To collect data on infant toxicity following maternal treatment with ddI during the third trimester of pregnancy.

AZT may not be the optimal antiretroviral agent for all pregnant women requiring therapy for HIV infection. Although ddI has been approved for use in HIV-infected adults and older children, the safety and pharmacokinetics of ddI in pregnant women has not yet been determined.

Detailed description: AZT may not be the optimal antiretroviral agent for all pregnant women requiring therapy for HIV infection. Although ddI has been approved for use in HIV-infected adults and older children, the safety and pharmacokinetics of ddI in pregnant women has not yet been determined.

Patients receive a single IV dose of ddI on day 1 and pharmacokinetics values are determined. At least 48 hours but no more than 1 week after the IV dose, patients receive an oral dose, and oral pharmacokinetics are obtained for 8 hours. Oral ddI is then administered every 12 hours until labor commences and then after delivery, every 12 hours until 6 weeks postpartum. During labor and delivery, patients receive a loading dose of ddI followed by continuous infusion. Pharmacokinetics are obtained during infusion and also at 6 weeks postpartum. AS PER AMENDMENT 11/24/97: Maternal IV pharmacokinetic studies will not be performed after ddI IV formulation has expired (11/30/97). Maternal and cord samples will be required regardless of whether mother has received continuous IV ddI during labor.

Eligibility criteria: Inclusion Criteria

Concurrent Medication:

Allowed:

* Aerosolized pentamidine.
* IV AZT during labor.

Patients must have:

* HIV infection.
* CD4 count \> 50 and \< 350 cells/mm3.
* AZT intolerance or resistance.
* Gestational age at least 26 weeks but not more than 36 weeks.
* Consent of guardian if necessary. The father of the fetus must also provide consent if available after reasonable attempts have been made to contact him.

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

* Multiple gestation.
* Current obstetrical complication, such as major anomalies, growth retardation, abnormal fluid level, fetal hydrops, or placental abruption (placenta previa is allowed).
* No access to a participating ACTU.

Concurrent Medication:

Excluded:

* Drugs that might aggravate pancreatitis, such as steroids, isoniazid, and parenteral pentamidine.
* Antiretrovirals other than ddI (although IV AZT is allowed during labor).

Patients with the following prior conditions are excluded:

* History of stillbirth, neonatal loss, or previous infant with anomaly (history of preeclampsia or preterm labor is permitted).
* History of maternal medical complications including but not limited to malabsorption syndrome, pancreatitis, neurological complications including grade 2 or worse peripheral neuropathy, symptomatic cholelithiasis, or prior active CMV disease requiring ganciclovir or foscarnet.
* History of poor medical compliance not related to access to medical care.

Prior Medication:

Excluded:

* ddI within 24 hours prior to study entry.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: UCLA-Los Angeles/Brazil AIDS Consortium (LABAC) CRS
state: California
city: San Diego
country: United States
facility: UCSD Maternal, Child, and Adolescent HIV CRS
state: California
city: Jacksonville
country: United States
facility: Univ. of Florida Jacksonville NICHD CRS
state: Florida
city: Miami
country: United States
facility: Univ. of Miami Ped. Perinatal HIV/AIDS CRS
state: Florida
city: Chicago
country: United States
facility: Rush Univ. Med. Ctr. ACTG CRS
state: Illinois
city: New Orleans
country: United States
facility: Tulane Univ. Health Science Ctr., Tulane Univ. Hosp. & Clinic
state: Louisiana
city: New Orleans
country: United States
facility: Tulane/LSU Maternal/Child CRS
state: Louisiana
city: Newark
country: United States
facility: NJ Med. School CRS
state: New Jersey
city: New York
country: United States
facility: Columbia IMPAACT CRS
state: New York
city: New York
country: United States
facility: Incarnation Children's Ctr.
state: New York
city: Durham
country: United States
facility: DUMC Ped. CRS
state: North Carolina
city: San Juan
country: Puerto Rico
facility: San Juan City Hosp. PR NICHD CRS
city: San Juan
country: Puerto Rico
facility: Univ. of Puerto Rico Ped. HIV/AIDS Research Program CRS
Study officials:
name: Livingston E
role: STUDY_CHAIR
name: Bartlett JA
role: STUDY_CHAIR
name: Unadkat J
role: STUDY_CHAIR
References:
citation: Livingston E, Patil S, Unadkat J, McKinney R, Abreu E, Bardequez A, O'Sullivan M. Placental transfer of didanosine (ddI) and initial evaluation of didanosine toxicity in HIV-1 infected pregnant women and their offspring. Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:121 (abstract no 226)
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: Patil SD, Livingston E, McKinney RE, Abreu E, O'Sullivan MJ, Bardequez A, Unadkat JD. Does pregnancy affect the pharmacokinetics of didanosine (ddI) in HIV-1 infected women? Conf Retroviruses Opportunistic Infect. 1998 Feb 1-5;5th:121 (abstract no 225)