The Antiviral Therapy in Pregnant Women to Reduce Mother-to-infant Transmission of Hepatitis B Virus-drug Test

Study Overview
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Brief Summary
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Since the implementation of universal vaccination in 1984, the chronic HBV carier rate in our general population reduced from 15-20%, down to < 1% in the post-vaccination population. However, children born to HBeAg positive mothers still may be infected with HBV despite immunization. To further reducing the HBV infection in our people, strategies in reducing infection rate in this high risk group are mandatory. Previous small scale studies using lamivudine treatment in pregnant woman in the third trimester has proved effective in reducing children infection rate. The aims of the present study are to conduct a clinical trial in using Tenofovir (category B) to reduce mother-to-infant transmission, and to monitor the hepaitits B viral status and mother hepatitis occurrence. The clinical trials will screen cases of HBsAg positive pregnant women aged 20 to 40 years at gestational at 20-32 weeks. They will be tested for HBsAg and HBeAg. In whom both markers are positive, HBV viral load will be tested. An estimated 180 pregnant women with high HBV viral load (>10^8 copies/mL) will be recruited in the study; including 80-100 subjects treated with Tenofovir 300 mg daily starting from 30-32 weeks of gestation (3rd trimester) and continued to 1 month after delivery; and 80-100 pregnant women are enrolled as controls with no drug given to the mother. The newborn babies are given with HBIG within 24 hours after delivery, and HBV vaccines at 0, 1 and 6 months. Maternal complete blood count (CBC) data tested in the first prenatal examination will be recorded. Plasma AST、ALT levels and HBV DNA are tested before Tenofovir treatment, 1 month after treatment, at the time of delivery, and at 1, 2, 4 and 6 months after delivery. HBsAg、HBeAg、anti-HBs and AST、ALT are tested in the children at day 1, 6 moths and 1 year after birth. The primary outcome is reduction of the HBsAg carrier rate of the children at 6 months of age. The secondary outcome is HBsAg carrier rate of the children at 12 months of age, the change of liver function, HBeAg, and viral load in pregnant mother after treatment. A follow-up study for investigating safety of mothers and children that has been exposed to maternal tenofovir disoproxil fumarate (TDF) during pregnancy in reducing mother-to-infant hepatitis B virus (HBV) transmissions is conducted. The follow-up study included mother-children pairs 2-4 years after delivery of the children.

Official Title
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The Effectiveness and Feasibility of Using Antiviral Therapy in Pregnant Women to Reduce Mother-to-infant Transmission of Hepatitis B Virus-drug Test and Follow-up Study

Conditions
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Hepatitis B Virus Infection, Pregnancy

Intervention / Treatment
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* Drug: antiviral therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: - pregnant women in 30 to 32 weeks of gestation, with positive HBsAg and HBeAg,serum viral load above 8log10 copies per mL Exclusion Criteria: major systemic disease Pregnant woman with infection of human immunodeficiency virus or hepatitis C virus Pregnant woman is receiving any drug with antiviral activity or any form of drug therapy for hepatitis B virus Pregnant woman whose ultrasonographic examination reveals congenital anomaly of the fetus Pregnant woman whose amniocentesis reveals any genetic abnormality

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: The effectiveness and feasibility, using antiviral therapy<br>Experimental: Subjects receive tenofovir disoproxil fumarate (TDF) oral use prior to delivery in pregnant women with positive serum HBeAg and HBsAg and high HBV DNA levels > 10^8copies / mL, to reduce the rate of mother to infant transmission of HBV infection, and also to monitor the safety of the therapy. | Drug: antiviral therapy<br>* 100-120 pregnant women seropositive for both HBeAg and HBsAg and with hepatitis B viral DNA level > 10 8 copies/mL. Among them, 55-65 pregnant women will receive TDF therapy 300 mg once daily, starting from the gestational age 30-32 (the 3rd trimester) until 4 weeks after delivery of the neonate under informed consent. The total treatment duration will be 3-4 months. Another 45-55 pregnant women with the same serum HBAg and HBsAg and HBV DNA status will be enrolled as the control group with no TDF therapy ( An open-labeled study)<br>|
| No Intervention: Control<br>Subjects receive no intervention, but with blood tests for mothers and infants before and after delivery, as a comparative group to experimental arm. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Child-HBsAg | serum status of HBsAg of the infants at 6 months old( >180 days). | 6 months after delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Child HBsAg | Serum HBsAg positivity of the infants at 12 months old, to see whether this child indeed becomes a chronic carrier of HBV. | 12 months after birth | 
| Children growth parameters | body weight and length Z score according to age | 0-5 years after birth | 
| Children HBV status | HBsAg and anti-HBs positivity rates | 0-5 years after birth | 
| Children serum biochemistry | Rates of abnormal levels of serum ALT(U/L), creatinine (mg/dL) and calcium (mmol/L) | 0-5 years after birth | 
| Maternal HBeAg seroconversion rate | Maternal HBeAg seroconversion rate, the time of HBeAg (+) to convert to HBeAg(-) after delivery | delivery to 5 years after delivery | 
| Maternal ALT elevation | The extent (folds of upper limit of normal, ULN) of ALT elevation and duration. | delivery to 5 years after delivery | 
| Maternal HBV DNA | Change of levels of HBV DNA (log IU/mL) from baseline | delivery to 5 years after delivery | 
| Children bone growth | comparisons of BAP levels(U/L) and bone density (DEXA) between control and treatment group | 2-5 years after birth | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hepatitis B virus,mother-infant transmission, nucleoside analog,pregnant women