Nevirapine Plus Zidovudine to Prevent Perinatal HIV in Thailand

NCT ID: NCT00398684

Last Updated: 2008-05-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

1792 participants

Study Classification

INTERVENTIONAL

Study Start Date

2001-01-31

Study Completion Date

2004-06-30

Brief Summary

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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.

Detailed Description

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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%.

Conditions

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HIV Infections Pregnancy

Keywords

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Thailand Developing countries prophylaxis mother to child transmission HIV-1 HIV-1 infection HIV Seronegativity

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

DOUBLE

Study Groups

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1

One dose maternal NVP treatment at onset of labor, and one dose of infant NVP treatment 48-72 hours after birth (NVP-NVP)

Group Type EXPERIMENTAL

Single dose nevirapine to the mother and to the child

Intervention Type DRUG

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. \[Infants less than 2,500g received only 0.2mL/kg\]

2

One dose maternal NVP treatment at onset of labor, and one dose of infant placebo 48-72 hours after birth. (NVP-Placebo)

Group Type EXPERIMENTAL

Single dose nevirapine to the mother and placebo to the child

Intervention Type DRUG

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. \[Infants less than 2,500g received only 0.2mL/kg\]

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)

Group Type PLACEBO_COMPARATOR

Single dose placebo to the mother and to the child

Intervention Type DRUG

One maternal placebo dose at the onset of labor, and one dose of infant placebo (0.6 ml) between 48-72 hours after birth. \[Infants less than 2,500g received only 0.2mL/kg\]

Interventions

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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. \[Infants less than 2,500g received only 0.2mL/kg\]

Intervention Type 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. \[Infants less than 2,500g received only 0.2mL/kg\]

Intervention Type 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. \[Infants less than 2,500g received only 0.2mL/kg\]

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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.


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.
Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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Harvard School of Public Health (HSPH)

OTHER

Sponsor Role collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

ANRS, Emerging Infectious Diseases

OTHER_GOV

Sponsor Role collaborator

Institut de Recherche pour le Developpement

OTHER_GOV

Sponsor Role lead

Principal Investigators

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Marc Lallemant, MD

Role: PRINCIPAL_INVESTIGATOR

Institut de Recherche pour le Developpement

Locations

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Phpt - Ird 174

Chiang Mai, Chiang Mai, Thailand

Site Status

Countries

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Thailand

References

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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.

Reference Type BACKGROUND
PMID: 15735445 (View on PubMed)

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. doi: 10.1056/NEJMoa041305. Epub 2004 Jul 9.

Reference Type BACKGROUND
PMID: 15247339 (View on PubMed)

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-child transmission of HIV-1 in Thailand. N Engl J Med. 2004 Jul 15;351(3):217-28. doi: 10.1056/NEJMoa033500. Epub 2004 Jul 9.

Reference Type RESULT
PMID: 15247338 (View on PubMed)

Sripan P, Le Coeur S, Amzal B, Ingsrisawang L, Traisathit P, Ngo-Giang-Huong N, McIntosh K, Cressey TR, Sangsawang S, Rawangban B, Kanjanavikai P, Treluyer JM, Jourdain G, Lallemant M, Urien S. Modeling of In-Utero and Intra-Partum Transmissions to Evaluate the Efficacy of Interventions for the Prevention of Perinatal HIV. PLoS One. 2015 May 19;10(5):e0126647. doi: 10.1371/journal.pone.0126647. eCollection 2015.

Reference Type DERIVED
PMID: 25992639 (View on PubMed)

Van Dyke RB, Ngo-Giang-Huong N, Shapiro DE, Frenkel L, Britto P, Roongpisuthipong A, Beck IA, Yuthavisuthi P, Prommas S, Puthanakit T, Achalapong J, Chotivanich N, Rasri W, Cressey TR, Maupin R, Mirochnick M, Jourdain G; IMPAACT P1032 Protocol Team. A comparison of 3 regimens to prevent nevirapine resistance mutations in HIV-infected pregnant women receiving a single intrapartum dose of nevirapine. Clin Infect Dis. 2012 Jan 15;54(2):285-93. doi: 10.1093/cid/cir798. Epub 2011 Dec 5.

Reference Type DERIVED
PMID: 22144539 (View on PubMed)

Related Links

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http://www.phpt.org

Program for HIV Prevention and Treatment (PHPT), Thailand

Other Identifiers

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PHPT-2; R01-HD39615; ANRS 1208

Identifier Type: -

Identifier Source: org_study_id