PHPT-5: Perinatal Antiretroviral Intensification for PMTCT of HIV in Late Comers

Sponsor

Institut de Recherche pour le Developpement (Other)

Overall Status

Completed

CT.gov ID

NCT01511237

Collaborator

Harvard School of Public Health (HSPH) (Other), Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) (NIH)

379

Enrollment

Locations

Arm

Duration (Months)

10.5

Patients Per Site

0.2

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The purpose is to evaluate the efficacy of maternal and infant perinatal antiretroviral prophylaxis intensification for the prevention of mother-to-child intrapartum transmission of HIV-1 in women receiving less than 8 weeks of antiretroviral prophylaxis during pregnancy.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Drug: Nevirapine, zidovudine, lamivudine	Phase 3

Detailed Description

Design: a multicenter, phase III, single-arm trial.

Perinatal antiretroviral intensification (study treatment) is defined as the addition to the standard of care* for mothers and infants of:

Mothers: One NVP 200 mg tablet at onset of labor with continuation of HAART for four weeks postpartum
Newborn: AZT+3TC+ NVP for 2 weeks, followed by AZT+3TC for 2 weeks:
NVP syrup 2 mg/kg every 24 hours for seven days, followed by NVP syrup 4 mg/kg every 24 hours for seven days. Newborns less than 2500 g will be administered 2mg/kg NVP syrup at each intake
AZT syrup 4 mg/ kg will be given every 12 hours for four weeks (preterm infants less than 30 weeks will be administered 2 mg/kg every 12 hours; preterm 30-35 weeks will receive 2 mg/kg every 12 hours for the first 2 weeks, increased to 3 mg/kg for the next 2 weeks).
3TC syrup 2 mg/kg every 12 hours for four weeks.
The standard of care in Thailand is defined as:
Maternal antiretroviral treatment: ZDV 300 mg, 3TC 150mg and LPV/r 400/100 twice a day starting as soon possible after 14 weeks of pregnancy + ZDV 300 mg every 3 hours during labor; this treatment may be continued, stopped or modified after delivery upon the recommendation of the internist.
Newborn: ZDV 4 mg/kg every 12 hours for 4 weeks (ZDV dosing adjusted for premature infants).

Study Design

Study Type:

Interventional

Actual Enrollment :

379 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

PHPT-5 Second Phase: Perinatal Antiretroviral Intensification for the Prevention of Mother-to-child Transmission of HIV in Thai Women Having Received Less Than 8 Weeks of HAART During Pregnancy

Study Start Date :

Dec 1, 2011

Actual Primary Completion Date :

Jun 1, 2015

Actual Study Completion Date :

Mar 1, 2017

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Perinatal intensification Perinatal antiretroviral intensification (study treatment): Mothers: One NVP 200 mg tablet at onset of labor with continuation of HAART for four weeks postpartum Newborn: AZT+3TC+ NVP for 2 weeks, followed by AZT+3TC for 2 weeks The standard of care in Thailand is defined as: Maternal: ZDV 300 mg, 3TC 150mg and LPV/r 400/100 twice a day starting as soon possible after 14 weeks of pregnancy + ZDV 300 mg every 3 hours during labor Newborn: ZDV 4 mg/kg every 12 hours for 4 weeks (ZDV dosing adjusted for premature infants).	Drug: Nevirapine, zidovudine, lamivudine Mothers: One NVP 200 mg tablet at onset of labor with continuation of HAART for four weeks postpartum Newborn: AZT+3TC+ NVP for 2 weeks, followed by AZT+3TC for 2 weeks: NVP syrup 2 mg/kg every 24 hours for seven days, followed by NVP syrup 4 mg/kg every 24 hours for seven days. Newborns less than 2500 g will be administered 2mg/kg NVP syrup at each intake AZT syrup 4 mg/ kg will be given every 12 hours for four weeks (preterm infants less than 30 weeks will be administered 2 mg/kg every 12 hours; preterm 30-35 weeks will receive 2 mg/kg every 12 hours for the first 2 weeks, increased to 3 mg/kg for the next 2 weeks). 3TC syrup 2 mg/kg every 12 hours for four weeks.

Arm

Intervention/Treatment

Experimental: Perinatal intensification

Perinatal antiretroviral intensification (study treatment): Mothers: One NVP 200 mg tablet at onset of labor with continuation of HAART for four weeks postpartum Newborn: AZT+3TC+ NVP for 2 weeks, followed by AZT+3TC for 2 weeks The standard of care in Thailand is defined as: Maternal: ZDV 300 mg, 3TC 150mg and LPV/r 400/100 twice a day starting as soon possible after 14 weeks of pregnancy + ZDV 300 mg every 3 hours during labor Newborn: ZDV 4 mg/kg every 12 hours for 4 weeks (ZDV dosing adjusted for premature infants).

Drug: Nevirapine, zidovudine, lamivudine

Mothers: One NVP 200 mg tablet at onset of labor with continuation of HAART for four weeks postpartum Newborn: AZT+3TC+ NVP for 2 weeks, followed by AZT+3TC for 2 weeks: NVP syrup 2 mg/kg every 24 hours for seven days, followed by NVP syrup 4 mg/kg every 24 hours for seven days. Newborns less than 2500 g will be administered 2mg/kg NVP syrup at each intake AZT syrup 4 mg/ kg will be given every 12 hours for four weeks (preterm infants less than 30 weeks will be administered 2 mg/kg every 12 hours; preterm 30-35 weeks will receive 2 mg/kg every 12 hours for the first 2 weeks, increased to 3 mg/kg for the next 2 weeks). 3TC syrup 2 mg/kg every 12 hours for four weeks.

Outcome Measures

Primary Outcome Measures

Rate of perinatal HIV transmission [6 months]
HIV DNA PCR analysis at birth, 2 weeks, 1, 2, 4 and 6 months of age

Secondary Outcome Measures

Safety for women and neonates [Up to 12 Months]
All grade 3 and 4 clinical adverse events and abnormal laboratory values in women will be recorded and graded according to the toxicity tables developed by the DAIDS
Pregnancy outcomes [Up to 12 Months]
Evaluation of the rates of live births and stillbirths, as well as birth weight, gestational age at delivery according to the results of the sonogram at first prenatal visit, newborn maturity (Ballard score).

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

Eligibility. Pregnant women presenting at the prenatal clinics will be eligible if they are confirmed HIV-infected, intend to deliver and bring their infant to a study site for postnatal care for at least 6 months; at least 18 years old; and have given written informed consent to participate in the study, regardless of their CD4 cell count.

Maternal inclusion criteria:

Evidence of HIV infection, as documented by two serology tests obtained at two different dates;
All HIV infected pregnant women will be enrolled, either in the intervention arm or an observational study group.
Women more than 30 weeks gestational age at start of antiretroviral treatment will be eligible for the intervention. They will actually receive the study intervention if they present in labor after less than 8 weeks of treatment duration;
Women with no ANC will receive standard care and will be enrolled in an observational study group(and their infant will receive standard of care perinatal antiretroviral intensification)
Women with less than 30 weeks gestational age at start of treatment will receive standard care and will also be enrolled in the Observational Reference group;
Agreement not to breastfeed;
Consent to participate and to be followed for the duration of the study

Exclusion Criteria:

Evidence of pre-existing fetal anomalies incompatible with life;
Concurrent participation to any other clinical trial without prior agreement of the two study teams

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Prapokklao Hospital	Chanthaburi	Chantaburi	Thailand	22000
2	Chomthong Hospital	Chom Thong	Chiang Mai	Thailand	50160
3	Fang Hospital	Fang	Chiang Mai	Thailand	50110
4	Nakornping Hospital	Mae Rim	Chiang Mai	Thailand	50180
5	Sanpatong Hospital	San Pa Tong	Chiang Mai	Thailand	50120
6	Mae Chan Hospital	Mae Chan	Chiang Rai	Thailand	57110
7	Phan Hospital	Phan	Chiang Rai	Thailand	57120
8	Chiangrai Prachanukroh Hospital	Chiang Rai	Chiangrai	Thailand	57000
9	Wiangpapao Hospital	Chiang Rai	Chiangrai	Thailand	57170
10	Chiang Saen Hospital	Chiang Saen	Chiangrai	Thailand	57150
11	Banglamung Hospital	Bang Lamung	Chonburi	Thailand	20150
12	Chonburi Hospital	Chon Buri	Chonburi	Thailand	20000
13	Panasnikom Hospital	Chon Buri	Chonburi	Thailand	20140
14	Mahasarakam Hospital	Maha Sarakham	Mahasarakam	Thailand	44000
15	Nakhonpathom Hospital	Nakhon Pathom	Nakhonpathom	Thailand	73000
16	Chiang Kham Hospital	Chiang Kham	Phayao	Thailand	56110
17	Buddhachinaraj Hospital	Phitsanulok	Pitsanuloke	Thailand	65000
18	Samutprakarn Hospital	Samut Prakan	Samutprakarn	Thailand	10280
19	Samutsakhon Hospital	Samut Sakhon	Samutsakhon	Thailand	74000
20	Hat Yai Hospital	Hat Yai	Songkla	Thailand	90110
21	Bhumibol Adulyadej Hospital	Bangkok		Thailand	10220
22	Nopparat Rajathanee Hospital	Bangkok		Thailand	10230
23	Bhuddasothorn Hospital	Chachoengsao		Thailand	24000
24	Health Promotion Center Region 10, Chiang Mai	Chiang Mai		Thailand	50100
25	Kalasin Hospital	Kalasin		Thailand	46000
26	Khon Kaen Hospital	Khon Kaen		Thailand	40000
27	Regional Health Promotion Centre 6, Khon Kaen	Khon Kaen		Thailand	40000
28	Lampang Hospital	Lampang		Thailand	52000
29	Lamphun Hospital	Lamphun		Thailand	51000
30	Maharaj Nakhon Si Thammarat Hospital	Nakhon Si Thammarat		Thailand	80000
31	Nong Khai Hospital	Nong Khai		Thailand	43000
32	Pranangklao Hospital	Nonthaburi		Thailand	11000
33	Phayao Provincial Hospital	Phayao		Thailand	56000
34	Vachira Phuket Hospital	Phuket		Thailand	83000
35	Rayong Hospital	Rayong		Thailand	21000
36	Songkhla Hospital	Songkhla		Thailand	90100

Sponsors and Collaborators

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