Shortened Zidovudine Regimens to Prevent Mother-to-Child Transmission of HIV Type 1

This study has been completed.
Sponsor:
Collaborators:
Harvard School of Public Health
Information provided by:
Institut de Recherche pour le Developpement
ClinicalTrials.gov Identifier:
NCT00386230
First received: October 10, 2006
Last updated: May 1, 2008
Last verified: May 2008
  Purpose

The purpose of the study was to test the equivalence of a short zidovudine (ZDV) regimen as compared to a longer, ACTG-076-like, ZDV regimen in reducing the risk of mother-to-child transmission of HIV: and to assess and compare the safety and tolerance of the long and shortened ZDV regimens.


Condition Intervention Phase
HIV Infections
Pregnancy
Drug: ZDV Short (mother)-Short (infant): Comparison of zidovudine durations
Drug: ZDV Short (mother)-Long (infant): Comparison of zidovudine durations
Drug: ZDV Long (mother)-Short (infant): Comparison of zidovudine durations
Drug: ZDV Long (mother)-Long (infant): Comparison of zidovudine durations
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Prevention
Official Title: Short ZDV Course to Prevent Perinatal HIV in Thailand

Resource links provided by NLM:


Further study details as provided by Institut de Recherche pour le Developpement:

Primary Outcome Measures:
  • Definitive HIV infection in children as assessed by positive PCR on two peripheral blood samples collected at two separate occasions.

Secondary Outcome Measures:
  • Safety: clinical and biological assessment.

Estimated Enrollment: 1554
Study Start Date: June 1997
Study Completion Date: August 2000
Arms Assigned Interventions
Experimental: 1
Maternal ZDV treatment starting at 35 weeks Gestational Age (GA) and continuing through labor and delivery, and three days of infant ZDV treatment starting at birth (Smother-Sinfant)
Drug: ZDV Short (mother)-Short (infant): Comparison of zidovudine durations
Maternal ZDV treatment (300 mg, twice daily) starting at 35 weeks Gestational Age (GA) until the onset of labor, ZDV 300 mg at the onset of labor and then 300 mg every 3 hours until delivery. Three days of infant ZDV treatment (2 mg/kg, every 6 hours) starting at birth (Smother-Sinfant)
Experimental: 2
Maternal ZDV treatment starting at 35 weeks Gestational Age (GA) and continuing through labor and delivery, and six weeks of infant ZDV treatment starting at birth (Smother-Linfant)
Drug: ZDV Short (mother)-Long (infant): Comparison of zidovudine durations
Maternal ZDV treatment (300 mg, twice daily) starting at 35 weeks Gestational Age (GA) until the onset of labor, ZDV 300 mg at the onset of labor and then 300 mg every 3 hours until delivery. Six weeks of infant ZDV treatment (2 mg/kg, every 6 hours) starting at birth (Smother-Linfant)
Experimental: 3
Maternal ZDV treatment starting at 28 weeks Gestational Age (GA) and continuing through labor and delivery, and three days of infant ZDV treatment starting at birth (Lmother-Sinfant)
Drug: ZDV Long (mother)-Short (infant): Comparison of zidovudine durations
Maternal ZDV treatment (300 mg, twice daily) starting at 28 weeks Gestational Age (GA) until the onset of labor, ZDV 300 mg at the onset of labor and then 300 mg every 3 hours until delivery. Three days of infant ZDV treatment (2 mg/kg, every 6 hours) starting at birth (Lmother-Sinfant)
Active Comparator: 4
Maternal ZDV treatment starting at 28 weeks Gestational Age (GA) and continuing through labor and delivery, and six weeks of infant ZDV treatment starting at birth (Lmother-Linfant). This study arm was the reference regimen.
Drug: ZDV Long (mother)-Long (infant): Comparison of zidovudine durations
Maternal ZDV treatment (300 mg, twice daily) starting at 28 weeks Gestational Age (GA) until the onset of labor, ZDV 300 mg at the onset of labor and then 300 mg every 3 hours until delivery. Six weeks of infant ZDV treatment (2 mg/kg, every 6 hours) starting at birth (Lmother-Linfant)

Detailed Description:

Multicenter, randomized, four arms, double-blind, controlled study. Consenting pregnant women were tested for HIV from the beginning of pregnancy until 26 of gestational age (GA). If HIV-positive and eligible, women completed a Pre-entry baseline check-up. Enrollment took place at 28 weeks' gestational age. Women meeting selection criteria were randomly assigned to one of four study arms (see below).

AMENDMENT (March 20, 1999)

Data Safety and Monitory Board interim review (March 17, 1999) The DSMB reported that the transmission rate in the longest arm (long treatment of both mother and baby), was significantly lower than that in the shortest arm (short treatment of both the mother and the baby) and this discrepancy was larger than the previously agreed on difference which, if found, would call for changing the study design. In addition, the transmission rates in the remaining two arms of the study were similar to that in the longest arm. The difference that was found could not be explained by any baseline characteristics of the participants, such as maternal age, gestational age at delivery, birth weight, cesarean section rate, or any others.

The DSMB recommended that enrollment into the shortest arm of the study be terminated, and the study be continued with a modification of design so that new enrollees would enter one of the three remaining arms.

All women enrolled before this amendment was effective and delivering after March 20th, 1999, and previously randomized to the Smother-Sinfant arm, were unblinded in order to give their infants open label zidovudine for 6 weeks.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Pre-inclusion

Women are eligible for Pre-Entry if they:

  • have evidence of HIV infection (confirmed on a second sample);
  • present themselves for prenatal care before 26 weeks GA, based on last menstrual period and/or sonogram results;
  • intend to stay in the province for at least 18 months after delivery;
  • can provide informed consent;
  • have given written informed consent to participate in the study;
  • intend to carry the pregnancy to term.

Inclusion Criteria:

  • all pre-entry criteria;
  • date of enrollment: 28 weeks GA, based on last menstrual period and/or sonogram results;
  • the following laboratory values within 21 days prior to randomization:
  • hemoglobin > 8.0 g/dL;
  • absolute neutrophil count > 750 cells/mm3;
  • SGPT < 5 x upper limit of normal;
  • serum creatinine < 1.5 mg/dL (women with a serum creatinine > 1.5 mg/dL must have a measured eight-hour urine creatinine clearance > 70 mL/min.);
  • agreement not to breastfeed.

Exclusion Criteria:

  • AIDS according to the Thai Communicable Diseases Control (CDC) classification;
  • pre-existing maternal/fetal condition that contraindicates the use of ZDV
  • oligohydramnios, unexplained polyhydramnios, fetal hydrops or ascites or other evidence of pre-existing in-utero anemia;
  • clinically significant history of intolerance to ZDV treatment resulting in discontinuation of therapy for more than 4 weeks;
  • receipt of ZDV during the current pregnancy for any indication, or women who need ZDV for their own health (women are then followed separately);
  • receipt of other antiretroviral agents, passive immunotherapy, anti-HIV vaccines, cytolytic agents (usually referred as chemotherapy), radiation therapy, or corticosteroids during this pregnancy except steroids less than 7 (see Zidovudine Investigator's Brochure);
  • simultaneous participation in another clinical trial.
  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: NCT00386230

Locations
Thailand
Phpt - Ird 174
Chiang Mai, Thailand, 50200
Sponsors and Collaborators
Institut de Recherche pour le Developpement
Harvard School of Public Health
Investigators
Principal Investigator: Marc Lallemant, MD Institut de Recherche pour le Developpement
  More Information

Publications:
ClinicalTrials.gov Identifier: NCT00386230     History of Changes
Other Study ID Numbers: PHPT-1, NIH 5 R01 HD33326-05
Study First Received: October 10, 2006
Last Updated: May 1, 2008
Health Authority: Thailand: Ministry of Public Health

Keywords provided by Institut de Recherche pour le Developpement:
transmission
infant
HIV
pregnancy
HIV-1 infection
HIV Seronegativity

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
Zidovudine
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Anti-HIV Agents

ClinicalTrials.gov processed this record on August 20, 2014