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

NCT ID: NCT00409591

Last Updated: 2016-01-28

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE3
• Total Enrollment: 435 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2015-06-30

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.

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.

Conditions

HIV Infections; Pregnancy

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: NONE

Study Groups

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

Group Type: ACTIVE_COMPARATOR

Maternal and infant nevirapine

Intervention Type: DRUG

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

zidovudine

Intervention Type: DRUG

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

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

Group Type: EXPERIMENTAL

Maternal placebo and infant nevirapine

Intervention Type: 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.

zidovudine

Intervention Type: DRUG

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

3

LPV/r:

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

Group Type: EXPERIMENTAL

Maternal lopinavir+ritonavir

Intervention Type: DRUG

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

zidovudine

Intervention Type: DRUG

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

Interventions

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

Intervention Type: 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.

Intervention Type: DRUG

Maternal lopinavir+ritonavir

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

Intervention Type: DRUG

zidovudine

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

Intervention Type: DRUG

Eligibility Criteria

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.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Harvard School of Public Health (HSPH)

OTHER

Sponsor Role: collaborator

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role: collaborator

Institut de Recherche pour le Developpement

OTHER_GOV

Sponsor Role: lead

Responsible Party

Marc Lallemant

Senior Researcher

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Marc Lallemant, MD

Role: PRINCIPAL_INVESTIGATOR

Institut de Recherche pour le Developpement

Locations

Health Promotion Hospital Regional Center I

Bangkok, Bangkok, Thailand

Nopparat Rajathanee Hospital

Kannayao, Bangkok, Thailand

Bhumibol Adulyadej Hospital

Saimai, Bangkok, Thailand

Chachoengsao Hospital

Muang, Changwat Chachoengsao, Thailand

Prapokklao Hospital

Muang, Changwat Chanthaburi, Thailand

Mae Chan Hospital

Mae Chan, Changwat Chiang Rai, Thailand

Mae Sai Hospital

Mae Sai, Changwat Chiang Rai, Thailand

Phan Hospital

Phan, Changwat Chiang Rai, Thailand

Banglamung Hospital

Bang Lamung, Changwat Chon Buri, Thailand

Somdej Pranangchao Sirikit Hospital

Chon Buri, Changwat Chon Buri, Thailand

Chonburi Hospital

Muang, Changwat Chon Buri, Thailand

Panasnikom Hospital

Panasnikom, Changwat Chon Buri, Thailand

Ao Udom Hospital

Si Racha, Changwat Chon Buri, Thailand

Kalasin Hospital

Muang, Changwat Kalasin, Thailand

Regional Health Promotion Centre 6,

Khon Kaen, Changwat Khon Kaen, Thailand

Khon Kaen Hospital

Muang, Changwat Khon Kaen, Thailand

Lampang Hospital

Lampang, Changwat Lampang, Thailand

Lamphun Hospital

Lamphun, Changwat Lamphun, Thailand

Maharaj Nakhon Si Thammarat Hospital

Muang, Changwat Nakhon Si Thammarat, Thailand

Nong Khai Hospital

Muang, Changwat Nong Khai, Thailand

Pranangklao Hospital

Muang, Changwat Nonthaburi, Thailand

Pathumthani Hospital

Muang, Changwat Pathum Thani, Thailand

Chiang Kham Hospital

Chiang Kham, Changwat Phayao, Thailand

Phayao Provincial Hospital

Phayao, Changwat Phayao, Thailand

Buddhachinaraj Hospital

Muang, Changwat Phitsanulok, Thailand

Rayong Hospital

Muang, Changwat Rayong, Thailand

Hat Yai Hospital

Hat Yai, Changwat Songkhla, Thailand

Songkhla Hospital

Muangsongkhla, Changwat Songkhla, Thailand

Trat Hospital

Muang, Changwat Trat, Thailand

Health Promotion Center Region 10,

Chiang Mai, Chiang Mai, Thailand

Nakornping Hospital

Mae Rim, Chiang Mai, Thailand

Sanpatong Hospital

Sanpatong, Chiang Mai, Thailand

Chiang Saen Hospital

Chiang Saen, Chiangrai, Thailand

Chiangrai Prachanukroh Hospital

Muang, Chiangrai, Thailand

Wiangpapao Hospital

Wiangpapao, Chiangrai, Thailand

Phaholpolphayuhasena Hospital

Munag, Kanchanaburi, Thailand

Mahasarakam Hospital

Muang, Mahasarakam, Thailand

Nakhonpathom Hospital

Muang, Nakhonpathom, Thailand

Samutprakarn Hospital

Samutprakarn, Samutprakarn, Thailand

Samutsakhon Hospital

Muang, Samutsakhon, Thailand

Fang Hospital

Chiang Mai, , Thailand

Chomthong Hospital

Chiang Mai, , Thailand

Vachira Phuket Hospital

Phuket, , Thailand

Countries

Thailand

References

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.

Reference Type: BACKGROUND

PMID: 15247338 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 15247339 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16816557 (View on PubMed)

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.

Reference Type: RESULT

PMID: 20625263 (View on PubMed)

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.

Reference Type: RESULT

PMID: 26372485 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 25992639 (View on PubMed)

Related Links

http://www.phpt.org

Program for HIV Prevention and Treatment (Thailand)

Other Identifiers

R01HD052461

Identifier Type: NIH

Identifier Source: secondary_id

View Link

R01HD056953

Identifier Type: NIH

Identifier Source: secondary_id

View Link

PHPT-5 First Phase

Identifier Type: -

Identifier Source: org_study_id