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)

This study has been terminated.
(Change in National PMTCT guidelines in Thailand)
Sponsor:
Collaborators:
Harvard School of Public Health
Information provided by (Responsible Party):
Marc Lallemant, Institut de Recherche pour le Developpement
ClinicalTrials.gov Identifier:
NCT00409591
First received: December 8, 2006
Last updated: July 24, 2014
Last verified: July 2014

December 8, 2006
July 24, 2014
July 2008
November 2010   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: No ]
Definitive HIV infection in infants as assessed by positive HIV DNA PCR on two peripheral blood samples
Complete list of historical versions of study NCT00409591 on ClinicalTrials.gov Archive Site
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 ] [ Designated as safety issue: Yes ]
Safety in neonates of two nevirapine doses with and without maternal single dose nevirapine at onset of labor.
Not Provided
Not Provided
 
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
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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
  • HIV Infections
  • Pregnancy
  • Drug: Maternal and infant nevirapine
    • In women, one NVP 200 mg tablet at onset of labor;
    • In neonates, NVP oral suspension 6 mg in the delivery room immediately
  • Drug: Maternal placebo and infant nevirapine
    • 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.

  • Drug: Maternal lopinavir+ritonavir
    - In women, LPV/r 400/100 mg bid from 28 weeks' gestation until delivery
  • Drug: zidovudine
    In addition, all women and infants in the 3 arms will receive standard ZDV prophylaxis, as per Thai and WHO guidelines.
  • 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
    Interventions:
    • Drug: Maternal and infant nevirapine
    • Drug: zidovudine
  • 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
    Interventions:
    • Drug: Maternal placebo and infant nevirapine
    • Drug: zidovudine
  • Experimental: 3

    LPV/r:

    • In women, LPV/r 400/100 mg bid from 28 weeks' gestation until delivery
    Interventions:
    • Drug: Maternal lopinavir+ritonavir
    • Drug: zidovudine

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Terminated
2097
December 2014
November 2010   (final data collection date for primary outcome measure)

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.

Both
Not Provided
No
Contact information is only displayed when the study is recruiting subjects
Thailand
 
NCT00409591
PHPT-5 First Phase, R01HD052461, R01HD056953
Yes
Marc Lallemant, Institut de Recherche pour le Developpement
Institut de Recherche pour le Developpement
  • Harvard School of Public Health
  • Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Principal Investigator: Marc Lallemant, MD Institut de Recherche pour le Developpment
Institut de Recherche pour le Developpement
July 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP