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

Sponsor

National Taiwan University Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT01312012

Collaborator

(none)

120

Enrollment

Location

Arms

131

Duration (Months)

0.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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.

Condition or Disease	Intervention/Treatment	Phase
Hepatitis B Virus Infection, Pregnancy	Drug: antiviral therapy	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

120 participants

Allocation:

Non-Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Study Start Date :

Jan 1, 2011

Anticipated Primary Completion Date :

Dec 1, 2021

Anticipated Study Completion Date :

Dec 1, 2021

Arms and Interventions

Arm	Intervention/Treatment
Experimental: The effectiveness and feasibility, using antiviral therapy 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 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)
No Intervention: Control Subjects receive no intervention, but with blood tests for mothers and infants before and after delivery, as a comparative group to experimental arm.

Arm

Intervention/Treatment

Experimental: The effectiveness and feasibility, using antiviral therapy

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

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)

No Intervention: Control

Subjects receive no intervention, but with blood tests for mothers and infants before and after delivery, as a comparative group to experimental arm.

Outcome Measures

Primary Outcome Measures

Child-HBsAg [6 months after delivery]
serum status of HBsAg of the infants at 6 months old( >180 days).

Secondary Outcome Measures

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

Eligibility Criteria

Criteria

Ages Eligible for Study:

20 Years to 40 Years

Sexes Eligible for Study:

Female

Accepts Healthy Volunteers:

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