Nevirapine Plus Zidovudine to Prevent Perinatal HIV in Thailand

HIV Infections Clinical Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00398684
• Other study ID #: PHPT-2; R01-HD39615; ANRS 1208
• Status: Completed
• Phase: Phase 3
• First received: November 13, 2006
• Last updated: May 2, 2008
• Start date: January 2001
• Est. completion date: June 2004

Study information

• Verified date: May 2008
• Source: Institut de Recherche pour le Developpement
• Contact: n/a
• Is FDA regulated: No
• Health authority: Thailand: Ministry of Public Health
• Study type: Interventional

Clinical Trial Summary

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.

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%.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1792
• Est. completion date: June 2004
• Accepts healthy volunteers: No
• Gender: Female
• Age group: N/A and older

Eligibility

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 Design

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

Related Conditions & MeSH terms

• HIV Infections
• Pregnancy

Intervention

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]
• 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]
• 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]

Locations

Country	Name	City	State
Thailand	Phpt - Ird 174	Chiang Mai

Sponsors (4)

Lead Sponsor	Collaborator
Institut de Recherche pour le Developpement	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), Harvard School of Public Health

Country where clinical trial is conducted

Thailand, 

References & Publications (3)

Cressey TR, Jourdain G, Lallemant MJ, Kunkeaw S, Jackson JB, Musoke P, Capparelli E, Mirochnick M. Persistence of nevirapine exposure during the postpartum period after intrapartum single-dose nevirapine in addition to zidovudine prophylaxis for the prevention of mother-to-child transmission of HIV-1. J Acquir Immune Defic Syndr. 2005 Mar 1;38(3):283-8. — View Citation

Jourdain G, Ngo-Giang-Huong N, Le Coeur S, Bowonwatanuwong C, Kantipong P, Leechanachai P, Ariyadej S, Leenasirimakul P, Hammer S, Lallemant M; Perinatal HIV Prevention Trial Group. Intrapartum exposure to nevirapine and subsequent maternal responses to nevirapine-based antiretroviral therapy. N Engl J Med. 2004 Jul 15;351(3):229-40. Epub 2004 Jul 9. — View Citation

Lallemant M, Jourdain G, Le Coeur S, Mary JY, Ngo-Giang-Huong N, Koetsawang S, Kanshana S, McIntosh K, Thaineua V; Perinatal HIV Prevention Trial (Thailand) Investigators. Single-dose perinatal nevirapine plus standard zidovudine to prevent mother-to-chil — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Definitive HIV infection in infants as assessed by positive HIV DNA PCR on two peripheral blood samples
Secondary	Tolerance of nevirapine, in particular rashes.

External Links

•   Program for HIV Prevention and Treatment (PHPT), Thailand