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

NCT00409591 | Terminated Phase 3 DMC

• 3 other identifiers: PHPT-5 First PhaseR01HD052461R01HD056953
• Study Type: interventional
• Target: 435
• Locations: 1 country
• Sites: 43

Brief Summary

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.

Conditions

HIV Infections; Pregnancy

Keywords

Thailand; Developing Countries; Prophylaxis; Mother-to-child transmission; HIV-1; HIV-1 infection; HIV Seronegativity

Outcome Measures

Primary Outcomes (1)

• Definitive HIV infection in infants as assessed by positive HIV DNA PCR on two peripheral blood samples

  At birth, 7-10 days, 1, 2, 4 and 6 months of age

Secondary Outcomes (1)

• 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.

  From randomization during pregnancy until 24 months after delivery

Study Arms (3)

1

ACTIVE COMPARATOR

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; Drug: zidovudine

2

EXPERIMENTAL

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; Drug: zidovudine

3

EXPERIMENTAL

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

Drug: Maternal lopinavir+ritonavir; Drug: zidovudine

Interventions

Maternal and infant nevirapine DRUG

* In women, one NVP 200 mg tablet at onset of labor; * In neonates, NVP oral suspension 6 mg in the delivery room immediately

1

Maternal placebo and infant nevirapine DRUG

* 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.

2

Maternal lopinavir+ritonavir DRUG

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

3

zidovudine DRUG

In addition, all women and infants in the 3 arms will receive standard ZDV prophylaxis, as per Thai and WHO guidelines.

1; 2; 3

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• Institut de Recherche pour le Developpement: lead
• Harvard School of Public Health (HSPH): collaborator
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator

Study Sites (43)

Health Promotion Hospital Regional Center I

Bangkok, Bangkok, 10220, Thailand

Location

Nopparat Rajathanee Hospital

Kannayao, Bangkok, 10230, Thailand

Location

Bhumibol Adulyadej Hospital

Saimai, Bangkok, Thailand

Location

Chachoengsao Hospital

Muang, Changwat Chachoengsao, 24000, Thailand

Location

Prapokklao Hospital

Muang, Changwat Chanthaburi, 22000, Thailand

Location

Mae Chan Hospital

Mae Chan, Changwat Chiang Rai, Thailand

Location

Mae Sai Hospital

Mae Sai, Changwat Chiang Rai, Thailand

Location

Phan Hospital

Phan, Changwat Chiang Rai, Thailand

Location

Banglamung Hospital

Bang Lamung, Changwat Chon Buri, 20150, Thailand

Location

Somdej Pranangchao Sirikit Hospital

Chon Buri, Changwat Chon Buri, 20180, Thailand

Location

Chonburi Hospital

Muang, Changwat Chon Buri, 20000, Thailand

Location

Panasnikom Hospital

Panasnikom, Changwat Chon Buri, 20140, Thailand

Location

Ao Udom Hospital

Si Racha, Changwat Chon Buri, 20230, Thailand

Location

Kalasin Hospital

Muang, Changwat Kalasin, 46000, Thailand

Location

Regional Health Promotion Centre 6,

Khon Kaen, Changwat Khon Kaen, 40000, Thailand

Location

Khon Kaen Hospital

Muang, Changwat Khon Kaen, Thailand

Location

Lampang Hospital

Lampang, Changwat Lampang, 52000, Thailand

Location

Lamphun Hospital

Lamphun, Changwat Lamphun, 51000, Thailand

Location

Maharaj Nakhon Si Thammarat Hospital

Muang, Changwat Nakhon Si Thammarat, 80000, Thailand

Location

Nong Khai Hospital

Muang, Changwat Nong Khai, 43000, Thailand

Location

Pranangklao Hospital

Muang, Changwat Nonthaburi, Thailand

Location

Pathumthani Hospital

Muang, Changwat Pathum Thani, 12000, Thailand

Location

Chiang Kham Hospital

Chiang Kham, Changwat Phayao, 56110, Thailand

Location

Phayao Provincial Hospital

Phayao, Changwat Phayao, 56000, Thailand

Location

Buddhachinaraj Hospital

Muang, Changwat Phitsanulok, Thailand

Location

Rayong Hospital

Muang, Changwat Rayong, 21000, Thailand

Location

Hat Yai Hospital

Hat Yai, Changwat Songkhla, 90110, Thailand

Location

Songkhla Hospital

Muangsongkhla, Changwat Songkhla, 90100, Thailand

Location

Trat Hospital

Muang, Changwat Trat, 23000, Thailand

Location

Health Promotion Center Region 10,

Chiang Mai, Chiang Mai, 50100, Thailand

Location

Nakornping Hospital

Mae Rim, Chiang Mai, 50180, Thailand

Location

Sanpatong Hospital

Sanpatong, Chiang Mai, Thailand

Location

Chiang Saen Hospital

Chiang Saen, Chiangrai, 57150, Thailand

Location

Chiangrai Prachanukroh Hospital

Muang, Chiangrai, 57000, Thailand

Location

Wiangpapao Hospital

Wiangpapao, Chiangrai, 57170, Thailand

Location

Phaholpolphayuhasena Hospital

Munag, Kanchanaburi, 71000, Thailand

Location

Mahasarakam Hospital

Muang, Mahasarakam, 44000, Thailand

Location

Nakhonpathom Hospital

Muang, Nakhonpathom, Thailand

Location

Samutprakarn Hospital

Samutprakarn, Samutprakarn, 10280, Thailand

Location

Samutsakhon Hospital

Muang, Samutsakhon, 74000, Thailand

Location

Fang Hospital

Chiang Mai, 50110, Thailand

Location

Chomthong Hospital

Chiang Mai, 50160, Thailand

Location

Vachira Phuket Hospital

Phuket, 83000, Thailand

Location

Related Publications (6)

• 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.

  PMID: 15247338 BACKGROUND

• 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.

  PMID: 15247339 BACKGROUND

• Shapiro RL, Thior I, Gilbert PB, Lockman S, Wester C, Smeaton LM, Stevens L, Heymann SJ, Ndung'u T, Gaseitsiwe S, Novitsky V, Makhema J, Lagakos S, Essex M. Maternal single-dose nevirapine versus placebo as part of an antiretroviral strategy to prevent mother-to-child HIV transmission in Botswana. AIDS. 2006 Jun 12;20(9):1281-8. doi: 10.1097/01.aids.0000232236.26630.35.

  PMID: 16816557 BACKGROUND

• Cressey TR, Jourdain G, Rawangban B, Varadisai S, Kongpanichkul R, Sabsanong P, Yuthavisuthi P, Chirayus S, Ngo-Giang-Huong N, Voramongkol N, Pattarakulwanich S, Lallemant M; PHPT-5 Team. Pharmacokinetics and virologic response of zidovudine/lopinavir/ritonavir initiated during the third trimester of pregnancy. AIDS. 2010 Sep 10;24(14):2193-200. doi: 10.1097/QAD.0b013e32833ce57d.

  PMID: 20625263 RESULT

• Lallemant M, Le Coeur S, Sirirungsi W, Cressey TR, Ngo-Giang-Huong N, Traisathit P, Klinbuayaem V, Sabsanong P, Kanjanavikai P, Jourdain G, Mcintosh K, Koetsawang S; PHPT-5 study investigators. Randomized noninferiority trial of two maternal single-dose nevirapine-sparing regimens to prevent perinatal HIV in Thailand. AIDS. 2015 Nov 28;29(18):2497-507. doi: 10.1097/QAD.0000000000000865.

  PMID: 26372485 RESULT

• 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 Jun 26;10(6):e0130917. doi: 10.1371/journal.pone.0130917. PLoS One. 2015 Aug 28;10(8):e0137368. doi: 10.1371/journal.pone.0137368.

  PMID: 25992639 DERIVED

Related Links

• Program for HIV Prevention and Treatment (Thailand)

MeSH Terms

Conditions

HIV Infections

Interventions

Zidovudine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases

Intervention Hierarchy (Ancestors)

Thymidine; Pyrimidine Nucleosides; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Dideoxynucleosides; Deoxyribonucleosides; Nucleosides; Nucleic Acids, Nucleotides, and Nucleosides

Study Officials

• Marc Lallemant, MD

  Institut de Recherche pour le Developpement

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Researcher

Study Record Dates

• First Submitted: December 8, 2006
• First Posted: December 11, 2006
• Study Start: July 1, 2008
• Primary Completion: November 1, 2010
• Study Completion: June 1, 2015
• Last Updated: January 28, 2016

Record last verified: 2016-01

Locations

TH (43)