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

HIV Infections Clinical Trial

— PHPT-5  

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.

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00409591
• Other study ID #: PHPT-5 First Phase
• Secondary ID: R01HD052461R01HD
• Status: Terminated
• Phase: Phase 3
• First received: December 8, 2006
• Last updated: January 26, 2016
• Start date: July 2008
• Est. completion date: June 2015

Study information

• Verified date: January 2016
• Source: Institut de Recherche pour le Developpement
• Contact: n/a
• Is FDA regulated: No
• Health authority: Thailand: Ministry of Public Health
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 435
• Est. completion date: June 2015
• Est. primary completion date: November 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Prevention

Related Conditions & MeSH terms

• HIV Infections
• Pregnancy

Intervention

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

Locations

Country	Name	City	State
Thailand	Health Promotion Hospital Regional Center I	Bangkok
Thailand	Banglamung Hospital	Banglamung	Chonburi
Thailand	Chiang Kham Hospital	Chiang Kham	Phayao
Thailand	Chomthong Hospital	Chiang Mai
Thailand	Fang Hospital	Chiang Mai
Thailand	Health Promotion Center Region 10,	Chiang Mai
Thailand	Chiang Saen Hospital	Chiang Saen	Chiangrai
Thailand	Somdej Pranangchao Sirikit Hospital	Chonburi
Thailand	Hat Yai Hospital	Hat Yai	Songkla
Thailand	Nopparat Rajathanee Hospital	Kannayao	Bangkok
Thailand	Regional Health Promotion Centre 6,	Khon Kaen
Thailand	Lamphun Hospital	Lamphun
Thailand	Mae Chan Hospital	Mae Chan	Chiang Rai
Thailand	Nakornping Hospital	Mae Rim	Chiang Mai
Thailand	Mae Sai Hospital	Mae Sai	Chiang Rai
Thailand	Buddhachinaraj Hospital	Muang	Pitsanulok
Thailand	Chachoengsao Hospital	Muang	Chachoengsao
Thailand	Chiangrai Prachanukroh Hospital	Muang	Chiangrai
Thailand	Chonburi Hospital	Muang	Chonburi
Thailand	Kalasin Hospital	Muang	Kalasin
Thailand	Khon Kaen Hospital	Muang	Khon Kaen
Thailand	Maharaj Nakhon Si Thammarat Hospital	Muang	Nakhon Si Thammarat
Thailand	Mahasarakam Hospital	Muang	Mahasarakam
Thailand	Nakhonpathom Hospital	Muang	Nakhonpathom
Thailand	Nong Khai Hospital	Muang	Nong Kai
Thailand	Pathumthani Hospital	Muang	Pathumthani
Thailand	Pranangklao Hospital	Muang	Nonthaburi
Thailand	Prapokklao Hospital	Muang	Chantaburi
Thailand	Rayong Hospital	Muang	Rayong
Thailand	Samutsakhon Hospital	Muang	Samutsakhon
Thailand	Trat Hospital	Muang	Trat
Thailand	Lampang Hospital	Muang, Lampang	Lampang
Thailand	Songkhla Hospital	Muangsongkhla	Songkhla
Thailand	Phaholpolphayuhasena Hospital	Munag	Kanjanaburi
Thailand	Panasnikom Hospital	Panasnikom	Chonburi
Thailand	Phan Hospital	Phan	Chiang Rai
Thailand	Phayao Provincial Hospital	Phayao
Thailand	Vachira Phuket Hospital	Phuket
Thailand	Bhumibol Adulyadej Hospital	Saimai	Bangkok
Thailand	Samutprakarn Hospital	Samutprakarn
Thailand	Sanpatong Hospital	Sanpatong	Chiang Mai
Thailand	Ao Udom Hospital	Sri Racha	Chonburi
Thailand	Wiangpapao Hospital	Wiangpapao	Chiangrai

Sponsors (3)

Lead Sponsor	Collaborator
Institut de Recherche pour le Developpement	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), Harvard School of Public Health

Country where clinical trial is conducted

Thailand, 

References & Publications (5)

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/rit — View Citation

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. Epub 2004 Jul 9. — View Citation

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. Epub 2004 Jul 9. — View Citation

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 n — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes

External Links

•   Program for HIV Prevention and Treatment (Thailand)