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
  Purpose

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.


Condition Intervention Phase
HIV Infections
Pregnancy
Drug: Maternal and infant nevirapine
Drug: Maternal placebo and infant nevirapine
Drug: Maternal lopinavir+ritonavir
Drug: zidovudine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
Official Title: 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.

Resource links provided by NLM:


Further study details as provided by Institut de Recherche pour le Developpement:

Primary Outcome Measures:
  • 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 ]

Secondary Outcome Measures:
  • 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 ]

Estimated Enrollment: 2097
Study Start Date: July 2008
Estimated Study Completion Date: December 2014
Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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
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: zidovudine
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
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: zidovudine
In addition, all women and infants in the 3 arms will receive standard ZDV prophylaxis, as per Thai and WHO guidelines.
Experimental: 3

LPV/r:

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

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.

  Eligibility

Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00409591

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

Additional Information:
Publications:
Responsible Party: Marc Lallemant, Senior Researcher, Institut de Recherche pour le Developpement
ClinicalTrials.gov Identifier: NCT00409591     History of Changes
Other Study ID Numbers: PHPT-5 First Phase, R01HD052461, R01HD056953
Study First Received: December 8, 2006
Last Updated: July 24, 2014
Health Authority: Thailand: Ministry of Public Health

Keywords provided by Institut de Recherche pour le Developpement:
Thailand
Developing Countries
Prophylaxis
Mother-to-child transmission
HIV-1
HIV-1 infection
HIV Seronegativity

Additional relevant MeSH terms:
Infection
HIV Infections
Acquired Immunodeficiency Syndrome
Lentivirus Infections
Retroviridae Infections
RNA Virus Infections
Virus Diseases
Sexually Transmitted Diseases, Viral
Sexually Transmitted Diseases
Immunologic Deficiency Syndromes
Immune System Diseases
Slow Virus Diseases
Ritonavir
Lopinavir
Zidovudine
Nevirapine
HIV Protease Inhibitors
Protease Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Anti-HIV Agents
Anti-Retroviral Agents
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Antimetabolites
Reverse Transcriptase Inhibitors
Nucleic Acid Synthesis Inhibitors

ClinicalTrials.gov processed this record on October 01, 2014