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.
18 Years
N/A
Female
Hepatitis B Chronic Infection, Pregnancy
Trial Information
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
exacerbation.
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.
Inclusion Criteria:
- Pregnancy
- At least 18 years of age
- Negative Human Immunodeficiency Virus (HIV) serology
- Positive HBsAg and HBeAg tests
- Gestational age of 28 weeks (+ or - 10 days) as determined by obstetrician
- ALT ≤30 U/L
- Agreeing to bring their infants at the planned study visits at one study site until
one year after delivery and to inform the site investigators if they plan to move to
another place and not be able to return to the clinic.
- Understanding the need for adequate infant immunization and agreeing to the blood
draws from their infants and the need for close follow up to manage possible
exacerbation of hepatitis.
Exclusion Criteria:
- History of anti-HBV antiviral treatment
- Creatinine clearance <50 ml/min, calculated using the Cockcroft-Gault formula
- Dipstick proteinuria>1+ (>30 mg/dL) or normoglycemic glucosuria confirmed on two
separate occasions
- Positive serology for Hepatitis C infection less than 12 months prior to enrollment
- Evidence of pre-existing fetal anomalies incompatible with life
- Any concomitant condition or treatment that, in the view of the clinical site
investigator, would contraindicate participation or satisfactory follow up in the
study.
- Concurrent participation in any other clinical trial without written agreement of the
two study teams
Type of Study:
Interventional
Study Design:
Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention
Outcome Measure:
Infant's Hepatitis B infection status, defined as HBsAg positive confirmed by HBV DNA
Outcome Time Frame:
6 months of age
Safety Issue:
No
Principal Investigator
Gonzague Jourdain, MD, PhD
Investigator Role:
Principal Investigator
Investigator Affiliation:
Institut de Recherche pour le Developpement
Authority:
Thailand: Ministry of Public Health
Study ID:
U01HD071889
NCT ID:
NCT01745822
Start Date:
January 2013
Completion Date:
December 2016
Related Keywords:
- Hepatitis B Chronic Infection
- Pregnancy
- Hepatitis B
- Hepatitis B sAg
- Hepatitis B eAg
- pregnancy
- Hepatitis
- Hepatitis A
- Hepatitis B
- Hepatitis B, Chronic
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