Nevirapine Plus Zidovudine to Prevent Perinatal HIV in Thailand

May 2, 2008 updated by: Institut de Recherche pour le Developpement
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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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%.

Study Type

Interventional

Enrollment

1792

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Thailand
      • Chiang Mai, Thailand, 50200
        • Phpt - Ird 174

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Child
  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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]

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Definitive HIV infection in infants as assessed by positive HIV DNA PCR on two peripheral blood samples

Secondary Outcome Measures

Outcome Measure
Tolerance of nevirapine, in particular rashes.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut de Recherche pour le Developpement

Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ANRS, Emerging Infectious Diseases
Harvard School of Public Health (HSPH)

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

January 1, 2001

Study Completion (Actual)

June 1, 2004

Study Registration Dates

First Submitted

November 13, 2006

First Submitted That Met QC Criteria

November 13, 2006

First Posted (Estimate)

November 14, 2006

Study Record Updates

Last Update Posted (Estimate)

May 7, 2008

Last Update Submitted That Met QC Criteria

May 2, 2008

Last Verified

May 1, 2008

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PHPT-2; R01-HD39615; ANRS 1208

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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