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.
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
Within 2 years, 328 women and their infants will be enrolled from public hospitals in
Thailand and randomized to receive either tenofovir or 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.
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Infant's Hepatitis B infection status, defined as HBsAg positive confirmed by HBV DNA
6 months of age
Gonzague Jourdain, MD, PhD
Institut de Recherche pour le Developpement
Thailand: Ministry of Public Health