Maternal Antiviral Prophylaxis to Prevent Perinatal Transmission of Hepatitis B Virus in Thailand (iTAP)
Chronic hepatitis B (CHB) infection is complicated by cirrhosis and liver cancer. In Thailand, 7% of adults are chronically infected by Hepatitis B virus (HBV). The risk of perinatal transmission of HBV is about 12% when a mother has a high HBV load in her plasma, even if her infant receive specific immunoglobulin and vaccine.
The hypothesis of this study is that a potent antiviral, tenofovir, can decrease HBV load in HBV infected pregnant women and therefore reduce the risk of perinatal transmission/ Pregnant women participating in this study will receive tenofovir or placebo during the last trimester of pregnancy and two months postpartum. The risk of perinatal transmission will be compared between the two groups.
The results of the study will help define policy to manage HBV infected pregnant women to prevent perinatal transmission.
Hepatitis B Chronic Infection
Drug: tenofovir disoproxil fumarate
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
|Official Title:||Phase 3, Randomized Clinical Trial to Assess the Efficacy and Safety of Tenofovir in Hepatitis B Virus Infected, s and e Antigen Positive, Pregnant Women to Prevent Perinatal Transmission Despite Infant Passive-active HBV Immunization.|
- Infant's Hepatitis B infection status at 6 months of age [ Time Frame: 6 months of age ] [ Designated as safety issue: No ]defined as HBsAg positive confirmed by HBV DNA
- Adverse events [ Time Frame: from enrollment (28 weeks' gestation) to 12 months postpartum ] [ Designated as safety issue: Yes ]Occurrence of maternal and infant adverse events, including maternal and infants Serious Adverse Events (as defined by the International Conference on Harmonization Good Clinical Practice) and NIH Division of AIDS grade 3/4 signs and symptoms, regardless of their relatedness to the study treatment.
- Flares after study treatment interruption [ Time Frame: Following planned discontinuation of study treatment up to 12 months postpartum ] [ Designated as safety issue: Yes ]Flare, or acute exacerbation of hepatitis B, after study treatment interruption is defined as an Alanine Aminotransferase plasma level above 300 IU/mL
- Infant's HBV infection status [ Time Frame: at or after 6 months through 12 months of age ] [ Designated as safety issue: No ]Infants will be considered HBV infected if at any time point at or after 6 months through 12 months of age, a sample tests positive for HBsAg and HBV DNA
- Infant growth related outcomes, including weight, height and HC Z-scores [ Time Frame: at 6 months and 12 months of age ] [ Designated as safety issue: Yes ]
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||October 2018|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Experimental: Tenofovir disoproxil fumarate
tenofovir disoproxil fumarate, 300 mg tablets
Drug: tenofovir disoproxil fumarate
administration: tablet 300 mg, once a day, from enrollment at 28 weeks' gestation until 2 months postpartum
Placebo Comparator: Placebo
matching placebo (of tenofovir disoproxil fumarate)
administration: one tablet, once a day, from enrollment at 28 weeks' gestation until 2 months postpartum
This is a phase III, placebo controlled, double blind, randomized clinical trial to assess the efficacy and safety of tenofovir disoproxil fumarate (TDF) given from 28 weeks' gestation until 2 months postpartum to pregnant women with Hepatitis B (HB) virus (HBV) chronic infection and positive for HB s and e antigen to prevent perinatal transmission of HBV to their infants. All infants will receive HBV passive (HB specific immunoglobulin) and active (vaccine) immunization.
Chronic hepatitis B (CHB) infection is complicated by cirrhosis and hepatocellular carcinoma (HCC), the 10th leading cause of death worldwide.
In 2011, about 7% of adults in Thailand were HBsAg carriers. Infant hepatitis B (HB) immunization and HB immune globulin (HBIg) administered at birth effectively prevent most mother-to-child transmission (MTCT) of HBV. However, about 12% of mothers with high load of HBV transmit the virus to their infants, despite active and passive immunization.
Studies have suggested that antiviral treatment at the end of pregnancy and during early postpartum can reduce the risk of transmission to the child. A potential limitation to this approach is the risk of hepatic disease exacerbation following discontinuation of antiviral treatment postpartum, and this risk has not been properly evaluated. No randomized clinical trials have adequately demonstrated the efficacy and safety of maternal antiviral treatment the prevention of mother to child transmission of HBV. This is the reason why this approach is not currently recommended by the Associations for the Study of Liver Diseases.
We hypothesize that a potent antiviral, tenofovir, can decrease HBV viral load in HBV infected pregnant women and therefore reduce the risk of perinatal transmission, before infants are definitely protected by passive-active immunization. We also hypothesize that only moderate exacerbations of liver disease will be observed after discontinuation of a short antiviral course (5 months). While the primary objective of the study is to assess the efficacy of tenofovir versus placebo for the prevention of perinatal transmission, an important secondary objective is the assessment of the risk of postpartum hepatic disease exacerbation.
Within 2 years, 328 women and their infants will be enrolled from public hospitals in Thailand and randomized to receive either tenofovir disoproxil fumarate or matching placebo from 28 weeks of pregnancy until 2 months postpartum. Mothers and infants will be followed until one year postpartum.
The primary endpoint will be the detection of HBsAg and HBV DNA in infants at six months of life. An interim analysis will be conducted when half of the outcomes are available.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01745822
|Mae Chan Hospital|
|Mae Chan, Chiangrai, Thailand, 57110|
|Banglamung, Chonburi, Thailand, 20150|
|Maharat Nakhon Ratchasima Hospital|
|Nakhon Ratchasima, Nakhon Ratchasrima, Thailand, 30000|
|Chiang Kham Hospital|
|Chiang Kham, Phayao, Thailand, 56110|
|Bhumibol Adulyadej Hospital|
|Bangkok, Thailand, 10220|
|Nopparat Rajathanee Hospital|
|Bangkok, Thailand, 10230|
|Chantaburi, Thailand, 22000|
|Health Promotion Center Region 10|
|Chiang Mai, Thailand, 50100|
|Chiang Mai, Thailand, 50180|
|Chiangrai Prachanukroh Hospital|
|Chiang Rai, Thailand, 57000|
|Chonburi Regional Hospital|
|Chonburi, Thailand, 20000|
|Khon Kaen Hospital|
|Khon Kaen, Thailand, 40000|
|Lampang, Thailand, 52000|
|Lamphun, Thailand, 51000|
|Phayao Provincial Hospital|
|Phayao, Thailand, 56000|
|Samutprakarn, Thailand, 10280|
|Samutsakorn, Thailand, 74000|
|Principal Investigator:||Gonzague Jourdain, MD, PhD||Institut de Recherche pour le Developpement|