Clinical trial NCT00409591: 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
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.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: HIV Infections
Pregnancy
Keywords: Thailand
Developing Countries
Prophylaxis
Mother-to-child transmission
HIV-1
HIV-1 infection
HIV Seronegativity
Lead sponsor: Institut de Recherche pour le Developpement
Sponsor class: OTHER_GOV
Collaborators: name: Harvard School of Public Health (HSPH)
name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
First posted: 2006-12-11
Enrollment: 435
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

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.

Eligibility 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.

Primary outcomes:
measure: Definitive HIV infection in infants as assessed by positive HIV DNA PCR on two peripheral blood samples
timeFrame: At birth, 7-10 days, 1, 2, 4 and 6 months of age
Secondary outcomes:
measure: 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.
timeFrame: From randomization during pregnancy until 24 months after delivery
Other outcomes:
Locations:
city: Kannayao
country: Thailand
facility: Nopparat Rajathanee Hospital
state: Bangkok
city: Saimai
country: Thailand
facility: Bhumibol Adulyadej Hospital
state: Bangkok
city: Muang
country: Thailand
facility: Chachoengsao Hospital
state: Chachoengsao
city: Muang
country: Thailand
facility: Prapokklao Hospital
state: Chantaburi
city: Mae Rim
country: Thailand
facility: Nakornping Hospital
state: Chiang Mai
city: Sanpatong
country: Thailand
facility: Sanpatong Hospital
state: Chiang Mai
city: Mae Chan
country: Thailand
facility: Mae Chan Hospital
state: Chiang Rai
city: Mae Sai
country: Thailand
facility: Mae Sai Hospital
state: Chiang Rai
city: Phan
country: Thailand
facility: Phan Hospital
state: Chiang Rai
city: Chiang Saen
country: Thailand
facility: Chiang Saen Hospital
state: Chiangrai
city: Muang
country: Thailand
facility: Chiangrai Prachanukroh Hospital
state: Chiangrai
city: Wiangpapao
country: Thailand
facility: Wiangpapao Hospital
state: Chiangrai
city: Banglamung
country: Thailand
facility: Banglamung Hospital
state: Chonburi
city: Muang
country: Thailand
facility: Chonburi Hospital
state: Chonburi
city: Panasnikom
country: Thailand
facility: Panasnikom Hospital
state: Chonburi
city: Sri Racha
country: Thailand
facility: Ao Udom Hospital
state: Chonburi
city: Muang
country: Thailand
facility: Kalasin Hospital
state: Kalasin
city: Munag
country: Thailand
facility: Phaholpolphayuhasena Hospital
state: Kanjanaburi
city: Muang
country: Thailand
facility: Khon Kaen Hospital
state: Khon Kaen
city: Muang, Lampang
country: Thailand
facility: Lampang Hospital
state: Lampang
city: Muang
country: Thailand
facility: Mahasarakam Hospital
state: Mahasarakam
city: Muang
country: Thailand
facility: Maharaj Nakhon Si Thammarat Hospital
state: Nakhon Si Thammarat
city: Muang
country: Thailand
facility: Nakhonpathom Hospital
state: Nakhonpathom
city: Muang
country: Thailand
facility: Nong Khai Hospital
state: Nong Kai
city: Muang
country: Thailand
facility: Pranangklao Hospital
state: Nonthaburi
city: Muang
country: Thailand
facility: Pathumthani Hospital
state: Pathumthani
city: Chiang Kham
country: Thailand
facility: Chiang Kham Hospital
state: Phayao
city: Muang
country: Thailand
facility: Buddhachinaraj Hospital
state: Pitsanulok
city: Muang
country: Thailand
facility: Rayong Hospital
state: Rayong
city: Muang
country: Thailand
facility: Samutsakhon Hospital
state: Samutsakhon
city: Muangsongkhla
country: Thailand
facility: Songkhla Hospital
state: Songkhla
city: Hat Yai
country: Thailand
facility: Hat Yai Hospital
state: Songkla
city: Muang
country: Thailand
facility: Trat Hospital
state: Trat
city: Bangkok
country: Thailand
facility: Health Promotion Hospital Regional Center I
city: Chiang Mai
country: Thailand
facility: Health Promotion Center Region 10,
city: Chiang Mai
country: Thailand
facility: Fang Hospital
city: Chiang Mai
country: Thailand
facility: Chomthong Hospital
city: Chonburi
country: Thailand
facility: Somdej Pranangchao Sirikit Hospital
city: Khon Kaen
country: Thailand
facility: Regional Health Promotion Centre 6,
city: Lamphun
country: Thailand
facility: Lamphun Hospital
city: Phayao
country: Thailand
facility: Phayao Provincial Hospital
city: Phuket
country: Thailand
facility: Vachira Phuket Hospital
city: Samutprakarn
country: Thailand
facility: Samutprakarn Hospital
Study officials:
affiliation: Institut de Recherche pour le Developpement
name: Marc Lallemant, MD
role: PRINCIPAL_INVESTIGATOR
References:
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. doi: 10.1056/NEJMoa033500. Epub 2004 Jul 9.
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. doi: 10.1056/NEJMoa041305. Epub 2004 Jul 9.
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. doi: 10.1097/01.aids.0000232236.26630.35.
citation: 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.
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 nevirapine-sparing regimens to prevent perinatal HIV in Thailand. AIDS. 2015 Nov 28;29(18):2497-507. doi: 10.1097/QAD.0000000000000865.
citation: 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.