A Study to Evaluate the Safety and Tolerance of Nelfinavir (NFV) Given With Zidovudine (ZDV) and Lamivudine (3TC) in HIV-Positive Pregnant Women and Their Infants

NCT ID: NCT00000887

Last Updated: 2021-10-29

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

24 participants

Study Classification

INTERVENTIONAL

Study Completion Date

2004-07-31

Brief Summary

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The purpose of this study is to see if giving nelfinavir (NFV) plus zidovudine (ZDV) plus lamivudine (3TC) to HIV-positive pregnant women and their babies is safe. This study will also look at how long these drugs stay in the blood.

ZDV has been given to mothers in the past to reduce the chances of passing HIV on to their babies. However, better treatments are needed to further reduce these chances and to better suit the treatment needs of mothers and their children. Taking a combination of anti-HIV drugs during pregnancy may be an answer.

Detailed Description

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Despite the dramatic reduction of perinatal HIV transmission by the administration of ZDV to mother and infant, new and more potent strategies are needed to further reduce perinatal transmission and better suit the diverse treatment needs of these patients. Initiation of triple antiretroviral combinations during gestation, particularly combinations that include drugs that cross the placenta such as 3TC, may be the most effective in reducing maternal virus load to its lowest levels prior to delivery.

Women receive nelfinavir plus 3TC plus ZDV antepartum (Study Day 0 until onset of active labor) through postpartum (after cord clamped to 12 weeks). \[AS PER AMENDMENT 10/28/97: If patient presents in active labor with less than 1 hour to delivery time, the institutional protocol for ZDV infusion during labor should be followed.\] \[AS PER AMENDMENT 1/26/99: For maternal dosing, one Combivir tablet bid can be substituted for the individual formulation of 3TC and ZDV. For mothers who receive Combivir during the antepartum period, Combivir is held during labor and delivery, and the separate formulations of ZDV and 3TC are used. Patients who prematurely discontinue study treatment should continue to be followed on study for the duration of the study.\] Full pharmacokinetic sampling is performed 10 to 15 days after start of therapy \[AS PER AMENDMENT 2/7/00: 10 to 15 days after study entry for women currently taking nelfinavir\] and again 5 to 6 weeks after delivery. A maternal blood sample and cord blood sample is collected at birth for analysis of nelfinavir concentrations. Maternal HIV RNA in plasma is monitored throughout the study. Cervicovaginal secretions are collected at entry, late gestation, and postpartum to assess the presence of HIV. A single pharmacokinetics sample is collected with each cervicovaginal secretion. Serial CD4/CD8 activation markers are measured in women during gestation and postpartum. Infants receive nelfinavir plus 3TC plus ZDV beginning approximately 12 hours following birth and continuing for 6 weeks. After birth, several blood samples are collected from the infant for determination of washout kinetics of nelfinavir. Full pharmacokinetics sampling is performed 5 to 8 days post birth and 5 to 6 weeks following multiple doses. Pharmacokinetic samples are analyzed on the first six mother-infant pairs and dosing may be adjusted accordingly for the next cohort. Agouron has agreed to make nelfinavir available to all interested study participants for a period of 6 months after the study via the patient assistance program.

Conditions

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HIV Infections Pregnancy

Keywords

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Pregnancy Pregnancy Complications, Infectious Drug Therapy, Combination Zidovudine HIV Protease Inhibitors Lamivudine Disease Transmission, Vertical Nelfinavir Anti-HIV Agents

Study Design

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Primary Study Purpose

TREATMENT

Interventions

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Nelfinavir mesylate

Intervention Type DRUG

Lamivudine

Intervention Type DRUG

Zidovudine

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Patients may be eligible for this study if they:

* Are at least 13 years old (need consent of parent or guardian if under 18).
* Are HIV-positive.
* Are in the 2nd or 3rd trimester (14 to 34 weeks pregnant) and are pregnant with one or two children.
* Have a normal ultrasound exam.

Exclusion Criteria

Patients will not be eligible for this study if they:

* Cannot take ZDV or 3TC.
* Have an active opportunistic (HIV-associated) or bacterial infection, or a severe medical condition.
* Have severe diarrhea.
* Are at risk for premature birth or pregnancy complications.
* Have a family history of phenylketonuria (PKU).
* Plan to breast-feed.
* Abuse alcohol or drugs.
* Cannot visit the same clinic for the duration of the study.
* Have taken certain anti-HIV drugs.
Minimum Eligible Age

13 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Yvonne Bryson

Role: STUDY_CHAIR

Mark Mirochnick

Role: STUDY_CHAIR

Alice Stek

Role: STUDY_CHAIR

Locations

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Usc La Nichd Crs

Los Angeles, California, United States

Site Status

Tulane Univ. Health Science Ctr., Tulane Univ. Hosp. & Clinic

New Orleans, Louisiana, United States

Site Status

Tulane/LSU Maternal/Child CRS

New Orleans, Louisiana, United States

Site Status

Johns Hopkins Hosp. & Health System - Dept. of Peds., Div. of Infectious Diseases

Baltimore, Maryland, United States

Site Status

HMS - Children's Hosp. Boston, Div. of Infectious Diseases

Boston, Massachusetts, United States

Site Status

UNC at Chapel Hill School of Medicine - Dept. of Peds., Div. of Immunology & Infectious Diseases

Chapel Hill, North Carolina, United States

Site Status

St. Christopher's Hosp. for Children

Philadelphia, Pennsylvania, United States

Site Status

Countries

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Puerto Rico United States

References

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Bryson Y, Stek A, Mirochnick M, et al. Pharmacokinetics, antiviral activity, and safety of nelfinavir (NFV) with ZDV/3TC in pregnant HIV-infected women and their infants. PACTG 353 cohort 2. 9th Conference on Retroviruses and Opportunistic Infections. 2002, February 24-28; Seattle Washington (abstract no 795)

Reference Type BACKGROUND

Bryson YJ, Mirochnick M, Stek A, Mofenson LM, Connor J, Capparelli E, Watts DH, Huang S, Hughes MD, Kaiser K, Purdue L, Asfaw Y, Keller M, Smith E; PACTG 353 Team. Pharmacokinetics and safety of nelfinavir when used in combination with zidovudine and lamivudine in HIV-infected pregnant women: Pediatric AIDS Clinical Trials Group (PACTG) Protocol 353. HIV Clin Trials. 2008 Mar-Apr;9(2):115-25. doi: 10.1310/hct0902-115.

Reference Type RESULT
PMID: 18474496 (View on PubMed)

Other Identifiers

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10603

Identifier Type: REGISTRY

Identifier Source: secondary_id

PACTG 353

Identifier Type: -

Identifier Source: secondary_id

ACTG 353

Identifier Type: -

Identifier Source: org_study_id