Maternal/Infant Peripartum NVP, Versus Infant Only Peripartum NVP, or Maternal LPV/r in Addition to Standard ZDV Prophylaxis for the Prevention of Perinatal (PMTCT) HIV in Thailand (PHPT-5)

January 26, 2016 updated by: Marc Lallemant, Institut de Recherche pour le Developpement

Maternal and Infant Peripartum Nevirapine, Versus Infant Only Peripartum Nevirapine, or Maternal Lopinavir/Ritonavir in Addition to Standard Zidovudine Prophylaxis for the Prevention of Perinatal HIV in Thailand.

The purpose of this study is to compare the efficacy of two doses of nevirapine (NVP) given only to the infants or lopinavir/ritonavir (LPV/r) from 28 weeks gestation with single dose (SD) NVP given to the mothers plus two doses to the infants, in addition to zidovudine (ZDV) prophylaxis (from 28 weeks' gestation and for one week of ZDV in neonates) for the prevention of mother-to-child transmission of HIV-1.

Study Overview

Detailed Description

Multicenter, placebo-controlled, double blind, clinical trial where non immunocompromised women receiving the ZDV prophylaxis regimen from 28 weeks gestation, as recommended in Thailand, will be randomized to one of two arms:

Arm 1: NVP-NVP:

  • In women, one NVP 200 mg tablet at onset of labor+;
  • In neonates, NVP oral suspension 6 mg in the delivery room immediately after birth plus a second dose between 48 and 72 hours+++

Arm 2: PL-NVP:

  • In women, one placebo tablet at onset of labor++;
  • In neonates, NVP oral suspension 6 mg in the delivery room immediately after birth plus a second dose between 48 and 72 hours+++

Arm 3: LPV/r:

  • In women, LPV/r 400/100 mg bid from 28 weeks' gestation until delivery

    • women in Arm 1 will also receive 7-day ZDV 300mg bid plus 3TC 150mg bid from delivery. ++women in Arm 2 will also receive 7-day (ZDV+3TC) Placebo from delivery. +++If the new born weight less than 2500 g, nevirapine will be administered 2 mg./1 kg (As per Thai Guideline).

All infants will receive ZDV for at least one week. Follow-up of women and infants is carried out on an outpatient basis except for delivery and the first three days after delivery. Mothers and infants are followed-up for 24 months after delivery.

Note: The study was stopped and data unblinded upon DSMB recommendations in September 2010 because of changes in Thai PMTCT guidelines recommending use of HAART in all HIV infected pregnant women regardless of their CD4 count. At the time of unblinding 435 pregnant women had been enrolled and follow-up of these women and their children is continuing.

Study Type

Interventional

Enrollment (Actual)

435

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

      • Bangkok, Thailand, 10220
        • Health Promotion Hospital Regional Center I
      • Chiang Mai, Thailand, 50100
        • Health Promotion Center Region 10,
      • Chiang Mai, Thailand, 50110
        • Fang Hospital
      • Chiang Mai, Thailand, 50160
        • Chomthong hospital
      • Chonburi, Thailand, 20180
        • Somdej Pranangchao Sirikit Hospital
      • Khon Kaen, Thailand, 40000
        • Regional Health Promotion Centre 6,
      • Lamphun, Thailand, 51000
        • Lamphun Hospital
      • Phayao, Thailand, 56000
        • Phayao Provincial Hospital
      • Phuket, Thailand, 83000
        • Vachira Phuket Hospital
      • Samutprakarn, Thailand, 10280
        • Samutprakarn Hospital
    • Bangkok
      • Kannayao, Bangkok, Thailand, 10230
        • Nopparat Rajathanee Hospital
      • Saimai, Bangkok, Thailand
        • Bhumibol Adulyadej Hospital
    • Chachoengsao
      • Muang, Chachoengsao, Thailand, 24000
        • Chachoengsao Hospital
    • Chantaburi
      • Muang, Chantaburi, Thailand, 22000
        • Prapokklao Hospital
    • Chiang Mai
      • Mae Rim, Chiang Mai, Thailand, 50180
        • Nakornping Hospital
      • Sanpatong, Chiang Mai, Thailand
        • Sanpatong Hospital
    • Chiang Rai
      • Mae Chan, Chiang Rai, Thailand
        • Mae Chan Hospital
      • Mae Sai, Chiang Rai, Thailand
        • Mae Sai Hospital
      • Phan, Chiang Rai, Thailand
        • Phan Hospital
    • Chiangrai
      • Chiang Saen, Chiangrai, Thailand, 57150
        • Chiang Saen Hospital
      • Muang, Chiangrai, Thailand, 57000
        • Chiangrai Prachanukroh Hospital
      • Wiangpapao, Chiangrai, Thailand, 57170
        • Wiangpapao Hospital
    • Chonburi
      • Banglamung, Chonburi, Thailand, 20150
        • Banglamung Hospital
      • Muang, Chonburi, Thailand, 20000
        • Chonburi Hospital
      • Panasnikom, Chonburi, Thailand, 20140
        • Panasnikom Hospital
      • Sri Racha, Chonburi, Thailand, 20230
        • Ao Udom Hospital
    • Kalasin
      • Muang, Kalasin, Thailand, 46000
        • Kalasin Hospital
    • Kanjanaburi
      • Munag, Kanjanaburi, Thailand, 71000
        • Phaholpolphayuhasena Hospital
    • Khon Kaen
      • Muang, Khon Kaen, Thailand
        • Khon Kaen Hospital
    • Lampang
      • Muang, Lampang, Lampang, Thailand, 52000
        • Lampang Hospital
    • Mahasarakam
      • Muang, Mahasarakam, Thailand, 44000
        • Mahasarakam Hospital
    • Nakhon Si Thammarat
      • Muang, Nakhon Si Thammarat, Thailand, 80000
        • Maharaj Nakhon Si Thammarat Hospital
    • Nakhonpathom
      • Muang, Nakhonpathom, Thailand
        • Nakhonpathom Hospital
    • Nong Kai
      • Muang, Nong Kai, Thailand, 43000
        • Nong Khai Hospital
    • Nonthaburi
      • Muang, Nonthaburi, Thailand
        • Pranangklao Hospital
    • Pathumthani
      • Muang, Pathumthani, Thailand, 12000
        • Pathumthani Hospital
    • Phayao
      • Chiang Kham, Phayao, Thailand, 56110
        • Chiang Kham Hospital
    • Pitsanulok
      • Muang, Pitsanulok, Thailand
        • Buddhachinaraj Hospital
    • Rayong
      • Muang, Rayong, Thailand, 21000
        • Rayong Hospital
    • Samutsakhon
      • Muang, Samutsakhon, Thailand, 74000
        • Samutsakhon Hospital
    • Songkhla
      • Muangsongkhla, Songkhla, Thailand, 90100
        • Songkhla Hospital
    • Songkla
      • Hat Yai, Songkla, Thailand, 90110
        • Hat Yai Hospital
    • Trat
      • Muang, Trat, Thailand, 23000
        • Trat Hospital

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

All

Description

Pre-Entry Criteria

  • Evidence of HIV infection (documented by two HIV antibody tests on two different dates)
  • Intend to be followed at a study site for the duration of the study
  • At least 18 years old
  • Written informed consent.

Inclusion Criteria:

Women are eligible for the study if they

  • met all pre-entry criteria
  • Evidence of HIV infection, as documented by two serology tests obtained at two different dates;
  • between 28 and 36 weeks gestational age;
  • antiretroviral naïve except for exposure to ZDV prophylaxis PMTCT;
  • CD4 count above 250 cells/mm3 (within 4 months prior to randomization)
  • agreement not to breastfeed;
  • consent to participate and to be followed for the duration of the study;
  • and the following laboratory values within 14 days prior to randomization:
  • hemoglobin > 8.5 mg/dl;
  • absolute neutrophil count > 750 cells/mm3;
  • platelets > 50,000 cells/mm3;
  • SGPT ≤ 5 times upper limit of normal;
  • serum creatinine ≤ 1.5 times upper limit of normal (women with a serum creatinine > 1.5 times upper limit of normal must have a measured eight-hour urine creatinine clearance > 70 ml/min).

Exclusion criteria:

  • Evidence of pre-existing fetal anomalies incompatible with life;
  • patients who meet the criteria of Classes III/IV of the WHO classification of HIV-associated clinical disease;
  • known hypersensitivity to any benzodiazepine;
  • active tuberculosis;
  • concurrent participation to any other clinical trial;
  • receipt of benzodiazepines or antiretroviral agent other than ZDV;
  • uncontrolled hypertension;
  • anticoagulant therapy or magnesium sulfate within 2 weeks of enrollment or the need for them during labor or at delivery.

If any of these conditions occurs after randomization, the women will be excluded from study drug dosing. Women with CD4 count lower than 250 cells/mm3 will be excluded from the study and offered HAART in the context of the national program.

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: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 1

NVP-NVP:

  • In women, one NVP 200 mg tablet at onset of labor;
  • In neonates, NVP oral suspension 6 mg in the delivery room immediately after birth plus a second dose between 48 and 72 hours
  • In women, one NVP 200 mg tablet at onset of labor;
  • In neonates, NVP oral suspension 6 mg in the delivery room immediately
In addition, all women and infants in the 3 arms will receive standard ZDV prophylaxis, as per Thai and WHO guidelines.
Experimental: 2

PL-NVP:

  • In women, one placebo tablet at onset of labor;
  • In neonates, NVP oral suspension 6 mg in the delivery room immediately after birth plus a second dose between 48 and 72 hours
In addition, all women and infants in the 3 arms will receive standard ZDV prophylaxis, as per Thai and WHO guidelines.
  • In women, one placebo tablet at onset of labor;
  • In neonates, NVP oral suspension 6 mg in the delivery room immediately after birth plus a second dose between 48 and 72 hours

Comparison between Arms 1 and 2 is double-blinded.

Experimental: 3

LPV/r:

  • In women, LPV/r 400/100 mg bid from 28 weeks' gestation until delivery
In addition, all women and infants in the 3 arms will receive standard ZDV prophylaxis, as per Thai and WHO guidelines.
- In women, LPV/r 400/100 mg bid from 28 weeks' gestation until delivery

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Definitive HIV infection in infants as assessed by positive HIV DNA PCR on two peripheral blood samples
Time Frame: At birth, 7-10 days, 1, 2, 4 and 6 months of age
At birth, 7-10 days, 1, 2, 4 and 6 months of age

Secondary Outcome Measures

Outcome Measure
Time Frame
Safety for mothers and children of two NVP doses in neonates with and without maternal single dose NVP at onset of labor or LPV/r from 28 weeks gestation.
Time Frame: From randomization during pregnancy until 24 months after delivery
From randomization during pregnancy until 24 months after delivery

Collaborators and Investigators

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

Investigators

  • Principal Investigator: Marc Lallemant, MD, Institut de Recherche pour le Developpment

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

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

July 1, 2008

Primary Completion (Actual)

November 1, 2010

Study Completion (Actual)

June 1, 2015

Study Registration Dates

First Submitted

December 8, 2006

First Submitted That Met QC Criteria

December 8, 2006

First Posted (Estimate)

December 11, 2006

Study Record Updates

Last Update Posted (Estimate)

January 28, 2016

Last Update Submitted That Met QC Criteria

January 26, 2016

Last Verified

January 1, 2016

More Information

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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