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Nevirapine Plus Zidovudine to Prevent Perinatal HIV in Thailand

Primary Purpose

HIV Infections, Pregnancy

Status
Completed
Phase
Phase 3
Locations
Thailand
Study Type
Interventional
Intervention
Single dose nevirapine to the mother and to the child
Single dose nevirapine to the mother and placebo to the child
Single dose placebo to the mother and to the child
Sponsored by
Institut de Recherche pour le Developpement
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for HIV Infections focused on measuring Thailand, Developing countries, prophylaxis, mother to child transmission, HIV-1, HIV-1 infection, HIV Seronegativity

Eligibility Criteria

undefined - undefined (Child, Adult, Older Adult)FemaleDoes not accept healthy volunteers

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.

Sites / Locations

  • Phpt - Ird 174

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Placebo Comparator

Arm Label

1

2

3

Arm Description

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

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

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)

Outcomes

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.

Full Information

First Posted
November 13, 2006
Last Updated
May 2, 2008
Sponsor
Institut de Recherche pour le Developpement
Collaborators
Harvard School of Public Health (HSPH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), ANRS, Emerging Infectious Diseases
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1. Study Identification

Unique Protocol Identification Number
NCT00398684
Brief Title
Nevirapine Plus Zidovudine to Prevent Perinatal HIV in Thailand
Study Type
Interventional

2. Study Status

Record Verification Date
May 2008
Overall Recruitment Status
Completed
Study Start Date
January 2001 (undefined)
Primary Completion Date
undefined (undefined)
Study Completion Date
June 2004 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Institut de Recherche pour le Developpement
Collaborators
Harvard School of Public Health (HSPH), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), ANRS, Emerging Infectious Diseases

4. Oversight

5. Study Description

Brief 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.
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: One dose maternal NVP treatment at onset of labor, and one dose of infant NVP treatment 48-72 hours after birth One dose maternal NVP treatment at onset of labor, and one dose of infant placebo 48-72 hours after birth 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%.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
HIV Infections, Pregnancy
Keywords
Thailand, Developing countries, prophylaxis, mother to child transmission, HIV-1, HIV-1 infection, HIV Seronegativity

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
Double
Allocation
Randomized
Enrollment
1792 (false)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
One dose maternal NVP treatment at onset of labor, and one dose of infant NVP treatment 48-72 hours after birth (NVP-NVP)
Arm Title
2
Arm Type
Experimental
Arm Description
One dose maternal NVP treatment at onset of labor, and one dose of infant placebo 48-72 hours after birth. (NVP-Placebo)
Arm Title
3
Arm Type
Placebo Comparator
Arm Description
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)
Intervention Type
Drug
Intervention Name(s)
Single dose nevirapine to the mother and to the child
Intervention Description
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
Intervention Name(s)
Single dose nevirapine to the mother and placebo to the child
Intervention Description
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
Intervention Name(s)
Single dose placebo to the mother and to the child
Intervention Description
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]
Primary Outcome Measure Information:
Title
Definitive HIV infection in infants as assessed by positive HIV DNA PCR on two peripheral blood samples
Secondary Outcome Measure Information:
Title
Tolerance of nevirapine, in particular rashes.

10. Eligibility

Sex
Female
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marc Lallemant, MD
Organizational Affiliation
Institut de Recherche pour le Developpement
Official's Role
Principal Investigator
Facility Information:
Facility Name
Phpt - Ird 174
City
Chiang Mai
ZIP/Postal Code
50200
Country
Thailand

12. IPD Sharing Statement

Citations:
PubMed Identifier
15735445
Citation
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.
Results Reference
background
PubMed Identifier
15247339
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. doi: 10.1056/NEJMoa041305. Epub 2004 Jul 9.
Results Reference
background
PubMed Identifier
15247338
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-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.
Results Reference
result
PubMed Identifier
25992639
Citation
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. Erratum In: PLoS One. 2015;10(6):e0130917. PLoS One. 2015;10(8):e0137368.
Results Reference
derived
PubMed Identifier
22144539
Citation
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.
Results Reference
derived
Links:
URL
http://www.phpt.org
Description
Program for HIV Prevention and Treatment (PHPT), Thailand

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Nevirapine Plus Zidovudine to Prevent Perinatal HIV in Thailand

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