Immunoprophylaxis with two hepatitis B vaccinations following the hepatitis B immune globulin (HBIg) and hepatitis B vaccine at birth is largely effective in protecting infants from hepatitis B virus (HBV) infection. However, hepatitis B infection due to immunoprophylaxis failure often occurs in approximately 10% of infants who are born to highly viremic mothers with HBeAg-positive. Maternal HBV DNA \> 200,000 IU/mL is the major independent risk for mother-to-child transmission (MTCT). A recent randomized controlled trial has shown that Tenofovir Disoproxil Fumarate (TDF) use during the third trimester of pregnancy could safely reduce the rate of MTCT with few adverse effects when combined with the administration of the standard immunoprophylaxis to the infants. However, HBIg is expensive and not available in many developing countries, resulting approximately 30% of infant infection when they received only HBV vaccination. The present study aims to investigate if highly viremic mothers who are treated with TDF from the second trimester to delivery in combination of infant's standard series of HBV vaccinations (omission of HBIg) have a comparable MTCT rates, when compared to those of mothers who receive TDF at the third trimester in combination of infant's standard HBV vaccinations and a birth dose of HBIg.
This is a multicenter, prospective, randomized, open-label and parallel two arm study starting from week 14-16 of pregnancy to post-partum week 28. The enrollment from approximately 7 centers will be in blocks for sample balance. By using the randomized table, 280 HBeAg-positive pregnant women with chronic hepatitis B (CHB) will be randomized in a 1:1 ratio in to two arms. Group assignments will be also stratified by the maternal HBV DNA levels \>9 log10 versus ≤ 9 log10 IU/mL. Group A: This is the experimental group. Participating mothers will receive TDF (oral 300 mg tablet daily) starting at gestational weeks 14-16 and continue until delivery. The mothers will be followed together with their infants until postpartum week 28. Infants will receive hepatitis B vaccine at birth (within 12 hours) and additional hepatitis B vaccine at the age of week 4 and week 24. HBIg will be omitted for the infants in this group. However, the birth dose of HBIg will be provided to infants born to mothers who have poor control of maternal viremia (i.e. the levels of HBV DNA \>200,000 IU/mL before delivery). Group B: This is the comparative group. Participating mothers will receive TDF (oral 300 mg tablet daily) starting at gestational weeks 28 and continue until delivery. Patients in group B will have similar follow-up schedules as those in the experimental group. Infants will receive hepatitis B vaccine plus HBIg at birth (within 12 hours) and additional hepatitis B vaccine at the age of week 4 and week 24.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
PREVENTION
Masking
NONE
Enrollment
280
All mothers will receive TDF therapy. However, group A will initiate TDF at the gestational week of 14-16, while group B will initiate TDF at the gestational week of 28. All infants will receive a series of three hepatitis B vaccines (at birth, age of weeks 4 and 24). In addition, the infants in the group B will receive HBIg injection at birth.
Beijing Youan Hospital, Capital Medical University
Beijing, Beijing Municipality, China
RECRUITINGSouthwest Hospital
Chongqing, Chongqing Municipality, China
RECRUITINGGuangzhou Women and Children's Medical Center, Guangzhou Medical University
Guangzhou, Guangdong, China
RECRUITINGThe Fifth Hospital of Shijiazhuang
Shijiazhuang, Hebei, China
RECRUITINGShijiazhuang Maternal and Child Health Care Hospital
Shijiazhuang, Hebei, China
RECRUITINGDepartment of Infectious Diseases, the First Affiliated Hospital of Xi'an Jiaotong University
Xi'an, Shaanxi, China
RECRUITINGThe Third People's Hospital of Shenzhen
Shenzhen, Shenzhen, China
RECRUITINGAssessment on the proportion of infants who are infected with hepatitis B at the age of 28 weeks in the two groups
Compare MTCT rates between the two study groups and demonstrate non-inferiority in efficacy. MTCT rate is defined as the proportion of infants with serum HBV DNA \>20 IU/mL and/or HBsAg positivity at 28 weeks of age.
Time frame: From the date of birth to age of 28 weeks.
Assessment on congenital defects and/or malformation rates in each infant group for comparison
Congenital defects and/or malformation rates are defined as the proportion of infants with the aforementioned abnormalities discovered during the study period.
Time frame: From the date of birth to age of 28 weeks.
Assessment on the reduction of maternal HBV DNA levels at delivery
Assess the reduction of maternal HBV DNA levels at delivery when compared to the baseline before initiating TDF.
Time frame: From the date of randomization until delivery.
Maternal serological outcomes during the study: Percentage of mothers who loss/seroconversion of HBsAg or/and HBeAg during the study
Assess the percentage of mothers who loss/seroconversion of HBsAg or/and HBeAg during the study.
Time frame: From the date of randomization until postpartum week 28.
Adverse events of both mothers and infants
Assess the percentage of mothers or infants who have adverse events during the study.
Time frame: From the date of screening until postpartum week 28.
Tolerability of TDF therapy: Percentage of mothers who discontinue on TDF therapy due to the adverse event(s) during the study
Assess the percentage of mothers who discontinue on TDF therapy due to the adverse event(s) during the study.
Time frame: From the date of randomization until delivery.
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