A Study to Evaluate the Safety and Tolerance of Stavudine (d4T) in Combination With Lamivudine (3TC) in HIV-Positive Pregnant Women and Their Infants

This study has been completed.
Sponsor:
Collaborator:
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier:
NCT00000878
First received: November 2, 1999
Last updated: May 17, 2012
Last verified: May 2012
  Purpose

The purpose of this study is to evaluate the safety and tolerance of 2 anti-HIV drugs, d4T and 3TC, given in combination to HIV-positive pregnant women and their infants.

Most HIV-positive pregnant women usually take the anti-HIV drug zidovudine (ZDV) to treat HIV and reduce the chances of giving HIV to their babies. It recently has been shown that a combination of drugs may be more effective than ZDV alone. This study tests the effectiveness of combinations of ZDV, d4T, and 3TC.


Condition Intervention Phase
HIV Infections
Pregnancy
Drug: Lamivudine
Drug: Stavudine
Drug: Zidovudine
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Primary Purpose: Treatment
Official Title: A Phase I/II, Open-Label Study to Evaluate the Safety, Tolerance and Pharmacokinetics of Stavudine (d4T) in Combination With Lamivudine (3TC) in HIV-Infected Pregnant Women and Their Infants

Resource links provided by NLM:


Further study details as provided by National Institute of Allergy and Infectious Diseases (NIAID):

Estimated Enrollment: 26
Study Completion Date: October 2001
  Hide Detailed Description

Detailed Description:

New antiretroviral agents or combinations are sought that are as efficacious as ZDV and that would be effective in reducing the rate of vertical transmission of HIV in women who have been long-term recipients of ZDV. d4T is a good candidate drug. It is a thymidine nucleoside analogue that inhibits replication of HIV at concentrations similar to those of ZDV which have anti-HIV activity. The demonstrated safety profile of d4T, the ease of administration, and, most importantly, preliminary efficacy data, especially in combination with 3TC, make this an excellent candidate combination for a Phase I perinatal trial.

Two cohorts of women and infants are enrolled in this study. The first five mother/infant pairs enrolled comprise Group I. Mothers enrolled in this group must allow their infants to receive ZDV. Eight mother/infant pairs are then enrolled in Group II; Group II infants are allocated into two groups: those whose mothers allow the administration of ZDV (Group IIA) and those whose mothers do not (Group IIB).

Group I:

Women:

Beginning at a minimum of 14 weeks gestation:

  1. Oral d4T until the start of active labor.
  2. Oral 3TC.

At the start of active labor (defined as regular uterine contractions resulting in cervical dilation [3-4 cm] and effacement [50-60%]) and during delivery:

  1. d4T administered IV as a loading dose followed by a continuous infusion until the umbilical cord is clamped.
  2. Oral 3TC if patient's previous dose of 3TC was administered at least 0.5h prior to onset of labor and additional dose of 3TC is administered and the time until next dose is scheduled accordingly.

Infants:

  1. d4T as a single oral dose on Day 6 (+/- 2 days) and on Day 42 (this dose can be given between Days 35 and 42, inclusive).
  2. Oral ZDV (or IV if unable to take oral dosing) for 6 weeks, beginning a maximum of 12 hours after birth.
  3. 3TC for 6 weeks, beginning a maximum of 12 hours after birth.

Group II:

Women:

Beginning at a minimum of 14 weeks gestation:

  1. Oral d4T until the umbilical cord is clamped.
  2. Oral 3TC.

At the start of active labor and through delivery:

Oral d4T and 3TC as above. If the last doses of d4T and 3TC were given at least 0.5 hours prior to onset of active labor, an additional dose of d4T and 3TC is given and repeated every 12 hours.

Infant Group IIA:

  1. d4T as a single oral dose on Day 6 (+/- 2 days) and on Day 42 (this dose can be given between Days 35 and 42, inclusive).
  2. Oral ZDV (or IV if unable to tolerate oral dosing) for 6 weeks, beginning a maximum of 12 hours after birth.
  3. 3TC for 6 weeks, beginning a maximum of 12 hours after birth.

Infant Group IIB:

Beginning a maximum of 12 hours after birth:

  1. d4T for 6 weeks.
  2. 3TC for 6 weeks. [AS PER AMENDMENT 9/15/97: If tolerated, infants continue on protocol treatment to 6 weeks of age. At 6 weeks, infants should receive standard care, including PCP prophylaxis, from an HIV specialist/pediatrician. HIV-infected infants are offered ACTG trial enrollment or open-label treatment based on best clinical judgment of their physician.] [AS PER AMENDMENT 2/19/99: Patients who prematurely discontinue study treatment should continue to be followed on study for the duration of the study.]
  Eligibility

Ages Eligible for Study:   13 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria

Women may be eligible for this study if they:

  • Are HIV-positive.
  • Are at least 13 years old (need consent of parent or guardian if under 18).
  • Are unable to or refuse to take ZDV or the woman's doctor says that she should take d4T.
  • Are 14 to 34 weeks pregnant.

Exclusion Criteria

Women will not be eligible for this study if they:

  • Have a history of peripheral neuropathy.
  • Have an active opportunistic infection and/or serious bacterial infection within 14 days of study entry.
  • Have severe diarrhea.
  • Are allergic to d4T or 3TC.
  • Use illicit drugs or abuse alcohol.
  • Are taking anti-HIV drugs other than study medications.
  • Are planning to breast-feed.
  • Are having a problem pregnancy (baby is not developing correctly or will not survive birth) or have had pregnancy complications in the past.
  • Babies will not be eligible for this study if they:
  • Are unable to take medications by mouth for more than 72 hours.
  • Have severe birth defects or other life-threatening conditions.
  • Are underweight (less than 2 kg).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00000878

Locations
United States, California
Harbor - UCLA Med Ctr / UCLA School of Medicine
Los Angeles, California, United States, 905022004
UCLA Med Ctr / Pediatric
Los Angeles, California, United States, 900951752
Los Angeles County - USC Med Ctr
Los Angeles, California, United States, 90033
United States, District of Columbia
Howard Univ Hosp
Washington, District of Columbia, United States, 20060
United States, Florida
Univ of Florida Health Science Ctr / Pediatrics
Jacksonville, Florida, United States, 32209
Univ of Miami / Jackson Memorial Hosp
Miami, Florida, United States, 33136
Univ of Miami (Pediatric)
Miami, Florida, United States, 33161
United States, Illinois
Univ of Chicago Children's Hosp
Chicago, Illinois, United States, 606371470
United States, Massachusetts
Brigham and Women's Hosp
Boston, Massachusetts, United States, 02115
Children's Hosp of Boston
Boston, Massachusetts, United States, 021155724
United States, New Jersey
Univ of Medicine & Dentistry of New Jersey / Univ Hosp
Newark, New Jersey, United States, 071032714
United States, New York
Children's Hosp at Albany Med Ctr
Albany, New York, United States, 12208
SUNY Health Sciences Ctr at Syracuse / Pediatrics
Syracuse, New York, United States, 13210
United States, North Carolina
Duke Univ Med Ctr
Durham, North Carolina, United States, 277103499
United States, Pennsylvania
Temple Univ School of Medicine
Philadelphia, Pennsylvania, United States, 191341095
United States, Tennessee
Saint Jude Children's Research Hosp of Memphis
Memphis, Tennessee, United States, 381052794
Regional Med Ctr at Memphis
Memphis, Tennessee, United States, 38103
United States, Washington
Children's Hospital & Medical Center / Seattle ACTU
Seattle, Washington, United States, 981050371
Puerto Rico
San Juan City Hosp
San Juan, Puerto Rico, 009367344
Univ of Puerto Rico / Univ Children's Hosp AIDS
San Juan, Puerto Rico, 009365067
Sponsors and Collaborators
Investigators
Study Chair: Nancy Wade
Study Chair: Sandra Burchett
Study Chair: Salih Yasin
Study Chair: Jash Unadkat
  More Information

Additional Information:
No publications provided

Responsible Party: National Institute of Allergy and Infectious Diseases (NIAID)
ClinicalTrials.gov Identifier: NCT00000878     History of Changes
Other Study ID Numbers: ACTG 332, 11304, PACTG 332
Study First Received: November 2, 1999
Last Updated: May 17, 2012
Health Authority: United States: Federal Government

Keywords provided by National Institute of Allergy and Infectious Diseases (NIAID):
Pregnancy
Pregnancy Complications, Infectious
Drug Therapy, Combination
Stavudine
Lamivudine
Disease Transmission, Vertical
Reverse Transcriptase Inhibitors
Anti-HIV Agents
Viral Load

Additional relevant MeSH terms:
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Lamivudine
Stavudine
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents
Antimetabolites

ClinicalTrials.gov processed this record on September 18, 2014