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Nevirapine Plus Zidovudine to Prevent Perinatal HIV in Thailand

This study has been completed.
Sponsor:
Collaborators:
Harvard School of Public Health
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Information provided by:
Institut de Recherche pour le Developpement
ClinicalTrials.gov Identifier:
NCT00398684
First received: November 13, 2006
Last updated: May 2, 2008
Last verified: May 2008
History of Changes
  Purpose

The purpose of this study was to assess the efficacy of a single dose of the drug nevirapine (NVP) given to pregnant women at onset of labor and to their infant 48-72 hours after birth in addition to standard oral zidovudine (ZDV or AZT) prophylaxis for the prevention of mother-to-child transmission of HIV-1.


Condition Intervention Phase
HIV Infections
Pregnancy
 Drug: Single dose nevirapine to the mother and to the child
Drug: Single dose nevirapine to the mother and placebo to the child
Drug: Single dose placebo to the mother and to the child
 Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double-Blind
Primary Purpose: Prevention

Resource links provided by NLM:

Drug Information available for: Nevirapine
U.S. FDA Resources

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

Primary Outcome Measures:
  • Definitive HIV infection in infants as assessed by positive HIV DNA PCR on two peripheral blood samples

Secondary Outcome Measures:
  • Tolerance of nevirapine, in particular rashes.

Estimated Enrollment: 1792
Study Start Date: January 2001
Study Completion Date: June 2004
Arms Assigned Interventions
Experimental: 1
One dose maternal NVP treatment at onset of labor, and one dose of infant NVP treatment 48-72 hours after birth (NVP-NVP)
 Drug: Single dose nevirapine to the mother and to the child
One maternal 200 mg NVP dose at the onset of labor, and one dose of infant NVP (0.6 ml/6mg) between 48-72 hours after birth. [Infants less than 2,500g received only 0.2mL/kg]
Experimental: 2
One dose maternal NVP treatment at onset of labor, and one dose of infant placebo 48-72 hours after birth. (NVP-Placebo)
 Drug: Single dose nevirapine to the mother and placebo to the child
One maternal 200 mg NVP dose at the onset of labor, and one dose of infant placebo (0.6 ml) between 48-72 hours after birth. [Infants less than 2,500g received only 0.2mL/kg]
Placebo Comparator: 3
One dose maternal placebo at onset of labor, and one dose of infant placebo 48-72 hours after birth. This was the reference study arm. (Placebo-Placebo)
 Drug: Single dose placebo to the mother and to the child
One maternal placebo dose at the onset of labor, and one dose of infant placebo (0.6 ml) between 48-72 hours after birth. [Infants less than 2,500g received only 0.2mL/kg]

Detailed Description:

Multicenter, randomized, three arms, double-blind, controlled study. Study population was HIV-infected pregnant women who were on ZDV prophylaxis for more than two weeks and gave informed consent. If eligible, women completed a baseline check-up. Women meeting selection criteria were randomly assigned to receive one of three study regimens, in addition to ZDV prophylaxis:

  1. One dose maternal NVP treatment at onset of labor, and one dose of infant NVP treatment 48-72 hours after birth
  2. One dose maternal NVP treatment at onset of labor, and one dose of infant placebo 48-72 hours after birth
  3. One dose maternal placebo at onset of labor, and one dose of infant placebo 48-72 hours after birth. This was the reference study arm.

Follow-up of women and infants was carried out on an outpatient basis except for delivery and the first three days after delivery.

AMENDMENT

After the first interim analysis, enrollment in Placebo-Placebo arm was terminated on May 2, 2002, according to the recommendation of the Data and Safety Monitoring Board. The target sample size was increased to 660, instead of 510, in each of the two remaining arms (N-N and N-P) to ensure enough power to test for non-inferiority between these arms with a limit of 2.5%.

  Eligibility

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

Pre-Entry Criteria

Women were eligible for the study if they:

  • have evidence of HIV infection (documented by two HIV antibody tests on two different dates);
  • were to be provided ZDV Prophylaxis (starting at 28 weeks or as soon as possible thereafter);
  • intended to carry the pregnancy to term;
  • intended to deliver at and bring their infant to a study site for at least 12 months after delivery; and
  • could provide informed consent.

Inclusion criteria

Women are eligible for the study if they:

  • met all pre-entry criteria;
  • agreed not to breastfeed;
  • consented to participate and to be followed for the duration of the study;
  • presented the following laboratory values within 14 days prior to randomization:
  • hemoglobin > 8.0 mg/dl
  • absolute neutrophil count > 1000 cells/mm3
  • platelets > 100,000 cells/mm3
  • 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)
  • SGPT less than 10 times the upper limit of normal NOTE: Women with a Grade 2 or Grade 3 SGPT value (between 2.6 and 10 times the upper limit of normal) were allowed on study; they were monitored monthly until delivery. If at any point their SGPT value rose to a Grade 4 (more than 10 times the upper limit of normal), they should not be dosed with the Study Drug.

Exclusion Criteria:

  • evidence of pre-existing fetal anomalies incompatible with life;
  • known hypersensitivity to any benzodiazepine or to NVP;
  • receipt of antiretroviral agent other than ZDV;
  • receipt of non-allowed concomitant treatment;
  • uncontrolled hypertension;
  • concurrent participation in another clinical trial;
  • women with a CD4 count <200/µL or history of oral candidiasis if they were not receiving PCP prophylaxis.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00398684

Locations
Thailand
Phpt - Ird 174
Chiang Mai, Thailand, 50200
Sponsors and Collaborators
Institut de Recherche pour le Developpement
Harvard School of Public Health
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
French National Institute for Health and Medical Research-French National Agency for Research on AIDS and Viral Hepatitis (Inserm-ANRS)
Investigators
Principal Investigator: Marc Lallemant, MD Institut de Recherche pour le Developpement
  More Information

Additional Information:
Program for HIV Prevention and Treatment (PHPT), Thailand  This link exits the ClinicalTrials.gov site

Publications:

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

ClinicalTrials.gov Identifier: NCT00398684     History of Changes
Other Study ID Numbers: PHPT-2; R01-HD39615; ANRS 1208
Study First Received: November 13, 2006
Last Updated: May 2, 2008
Health Authority: Thailand: Ministry of Public Health

Keywords provided by Institut de Recherche pour le Developpement:
Thailand
Developing countries
prophylaxis
mother to child transmission
 HIV-1
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
 Nevirapine
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on March 14, 2013