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)
26 januari 2016 uppdaterad av: Marc Lallemant, Institut de Recherche pour le Developpement
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.
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.
Studieöversikt
Status
Avslutad
Betingelser
Detaljerad beskrivning
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.
Studietyp
Interventionell
Inskrivning (Faktisk)
435
Fas
- Fas 3
Kontakter och platser
Det här avsnittet innehåller kontaktuppgifter för dem som genomför studien och information om var denna studie genomförs.
Studieorter
-
-
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Bangkok, Thailand, 10220
- Health Promotion Hospital Regional Center I
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Chiang Mai, Thailand, 50100
- Health Promotion Center Region 10,
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Chiang Mai, Thailand, 50110
- Fang Hospital
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Chiang Mai, Thailand, 50160
- Chomthong hospital
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Chonburi, Thailand, 20180
- Somdej Pranangchao Sirikit Hospital
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Khon Kaen, Thailand, 40000
- Regional Health Promotion Centre 6,
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Lamphun, Thailand, 51000
- Lamphun Hospital
-
Phayao, Thailand, 56000
- Phayao Provincial Hospital
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Phuket, Thailand, 83000
- Vachira Phuket Hospital
-
Samutprakarn, Thailand, 10280
- Samutprakarn Hospital
-
-
Bangkok
-
Kannayao, Bangkok, Thailand, 10230
- Nopparat Rajathanee Hospital
-
Saimai, Bangkok, Thailand
- Bhumibol Adulyadej Hospital
-
-
Chachoengsao
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Muang, Chachoengsao, Thailand, 24000
- Chachoengsao Hospital
-
-
Chantaburi
-
Muang, Chantaburi, Thailand, 22000
- Prapokklao Hospital
-
-
Chiang Mai
-
Mae Rim, Chiang Mai, Thailand, 50180
- Nakornping Hospital
-
Sanpatong, Chiang Mai, Thailand
- Sanpatong Hospital
-
-
Chiang Rai
-
Mae Chan, Chiang Rai, Thailand
- Mae Chan Hospital
-
Mae Sai, Chiang Rai, Thailand
- Mae Sai Hospital
-
Phan, Chiang Rai, Thailand
- Phan Hospital
-
-
Chiangrai
-
Chiang Saen, Chiangrai, Thailand, 57150
- Chiang Saen Hospital
-
Muang, Chiangrai, Thailand, 57000
- Chiangrai Prachanukroh Hospital
-
Wiangpapao, Chiangrai, Thailand, 57170
- Wiangpapao Hospital
-
-
Chonburi
-
Banglamung, Chonburi, Thailand, 20150
- Banglamung Hospital
-
Muang, Chonburi, Thailand, 20000
- Chonburi hospital
-
Panasnikom, Chonburi, Thailand, 20140
- Panasnikom Hospital
-
Sri Racha, Chonburi, Thailand, 20230
- Ao Udom Hospital
-
-
Kalasin
-
Muang, Kalasin, Thailand, 46000
- Kalasin Hospital
-
-
Kanjanaburi
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Munag, Kanjanaburi, Thailand, 71000
- Phaholpolphayuhasena Hospital
-
-
Khon Kaen
-
Muang, Khon Kaen, Thailand
- Khon Kaen Hospital
-
-
Lampang
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Muang, Lampang, Lampang, Thailand, 52000
- Lampang Hospital
-
-
Mahasarakam
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Muang, Mahasarakam, Thailand, 44000
- Mahasarakam Hospital
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Nakhon Si Thammarat
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Muang, Nakhon Si Thammarat, Thailand, 80000
- Maharaj Nakhon Si Thammarat Hospital
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Nakhonpathom
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Muang, Nakhonpathom, Thailand
- Nakhonpathom Hospital
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Nong Kai
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Muang, Nong Kai, Thailand, 43000
- Nong Khai Hospital
-
-
Nonthaburi
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Muang, Nonthaburi, Thailand
- Pranangklao Hospital
-
-
Pathumthani
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Muang, Pathumthani, Thailand, 12000
- Pathumthani Hospital
-
-
Phayao
-
Chiang Kham, Phayao, Thailand, 56110
- Chiang Kham Hospital
-
-
Pitsanulok
-
Muang, Pitsanulok, Thailand
- Buddhachinaraj Hospital
-
-
Rayong
-
Muang, Rayong, Thailand, 21000
- Rayong Hospital
-
-
Samutsakhon
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Muang, Samutsakhon, Thailand, 74000
- Samutsakhon Hospital
-
-
Songkhla
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Muangsongkhla, Songkhla, Thailand, 90100
- Songkhla Hospital
-
-
Songkla
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Hat Yai, Songkla, Thailand, 90110
- Hat Yai hospital
-
-
Trat
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Muang, Trat, Thailand, 23000
- Trat Hospital
-
-
Deltagandekriterier
Forskare letar efter personer som passar en viss beskrivning, så kallade behörighetskriterier. Några exempel på dessa kriterier är en persons allmänna hälsotillstånd eller tidigare behandlingar.
Urvalskriterier
Åldrar som är berättigade till studier
- Barn
- Vuxen
- Äldre vuxen
Tar emot friska volontärer
Nej
Kön som är behöriga för studier
Allt
Beskrivning
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.
Studieplan
Det här avsnittet ger detaljer om studieplanen, inklusive hur studien är utformad och vad studien mäter.
Hur är studien utformad?
Designdetaljer
- Primärt syfte: Förebyggande
- Tilldelning: Randomiserad
- Interventionsmodell: Parallellt uppdrag
- Maskning: Ingen (Open Label)
Vapen och interventioner
Deltagargrupp / Arm |
Intervention / Behandling |
|---|---|
|
Aktiv komparator: 1
NVP-NVP:
|
In addition, all women and infants in the 3 arms will receive standard ZDV prophylaxis, as per Thai and WHO guidelines.
|
|
Experimentell: 2
PL-NVP:
|
In addition, all women and infants in the 3 arms will receive standard ZDV prophylaxis, as per Thai and WHO guidelines.
Comparison between Arms 1 and 2 is double-blinded. |
|
Experimentell: 3
LPV/r:
|
In addition, all women and infants in the 3 arms will receive standard ZDV prophylaxis, as per Thai and WHO guidelines.
- In women, LPV/r 400/100 mg bid from 28 weeks' gestation until delivery
|
Vad mäter studien?
Primära resultatmått
Resultatmått |
Tidsram |
|---|---|
|
Definitive HIV infection in infants as assessed by positive HIV DNA PCR on two peripheral blood samples
Tidsram: At birth, 7-10 days, 1, 2, 4 and 6 months of age
|
At birth, 7-10 days, 1, 2, 4 and 6 months of age
|
Sekundära resultatmått
Resultatmått |
Tidsram |
|---|---|
|
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.
Tidsram: From randomization during pregnancy until 24 months after delivery
|
From randomization during pregnancy until 24 months after delivery
|
Samarbetspartners och utredare
Det är här du hittar personer och organisationer som är involverade i denna studie.
Samarbetspartners
Utredare
- Huvudutredare: Marc Lallemant, MD, Institut de Recherche pour le Developpment
Publikationer och användbara länkar
Den som ansvarar för att lägga in information om studien tillhandahåller frivilligt dessa publikationer. Dessa kan handla om allt som har med studien att göra.
Allmänna publikationer
- 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.
- 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.
- 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.
- 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.
- 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.
- 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;10(6):e0130917. PLoS One. 2015;10(8):e0137368.
Användbara länkar
Studieavstämningsdatum
Dessa datum spårar framstegen för inlämningar av studieposter och sammanfattande resultat till ClinicalTrials.gov. Studieposter och rapporterade resultat granskas av National Library of Medicine (NLM) för att säkerställa att de uppfyller specifika kvalitetskontrollstandarder innan de publiceras på den offentliga webbplatsen.
Studera stora datum
Studiestart
1 juli 2008
Primärt slutförande (Faktisk)
1 november 2010
Avslutad studie (Faktisk)
1 juni 2015
Studieregistreringsdatum
Först inskickad
8 december 2006
Först inskickad som uppfyllde QC-kriterierna
8 december 2006
Första postat (Uppskatta)
11 december 2006
Uppdateringar av studier
Senaste uppdatering publicerad (Uppskatta)
28 januari 2016
Senaste inskickade uppdateringen som uppfyllde QC-kriterierna
26 januari 2016
Senast verifierad
1 januari 2016
Mer information
Termer relaterade till denna studie
Nyckelord
Ytterligare relevanta MeSH-villkor
- RNA-virusinfektioner
- Virussjukdomar
- Infektioner
- Blodburna infektioner
- Smittsamma sjukdomar
- Sexuellt överförbara sjukdomar, virala
- Sexuellt överförbara sjukdomar
- Lentivirusinfektioner
- Retroviridae-infektioner
- Immunologiska bristsyndrom
- Immunsystemets sjukdomar
- HIV-infektioner
- Molekylära mekanismer för farmakologisk verkan
- Anti-infektionsmedel
- Antivirala medel
- Omvända transkriptashämmare
- Nukleinsyrasynteshämmare
- Enzyminhibitorer
- Anti-HIV-medel
- Antiretrovirala medel
- Antimetaboliter
- Proteashämmare
- Cytokrom P-450 CYP3A-hämmare
- Cytokrom P-450 enzymhämmare
- Cytokrom P-450 enzyminducerare
- Cytokrom P-450 CYP3A-inducerare
- HIV-proteashämmare
- Virala proteashämmare
- Nevirapin
- Ritonavir
- Lopinavir
- Zidovudin
Andra studie-ID-nummer
- PHPT-5 First Phase
- R01HD052461 (U.S.S. NIH-anslag/kontrakt)
- R01HD056953 (U.S.S. NIH-anslag/kontrakt)
Läkemedels- och apparatinformation, studiedokument
Studerar en amerikansk FDA-reglerad läkemedelsprodukt
Nej
Studerar en amerikansk FDA-reglerad produktprodukt
Nej
produkt tillverkad i och exporterad från U.S.A.
Nej
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