Clinical trial NCT01312012: The Antiviral Therapy in Pregnant Women to Reduce Mother-to-infant Transmission of Hepatitis B Virus-drug Test
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 type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Hepatitis B Virus Infection, Pregnancy
Keywords: hepatitis B virus,mother-infant transmission, nucleoside analog,pregnant women
Lead sponsor: National Taiwan University Hospital
Sponsor class: OTHER
First posted: 2011-03-10
Enrollment: 120
Sex: FEMALE
Minimum age (years): 20
Maximum age (years): 40
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Child-HBsAg
timeFrame: 6 months after delivery
Secondary outcomes:
measure: Child HBsAg
timeFrame: 12 months after birth
measure: Children growth parameters
timeFrame: 0-5 years after birth
measure: Children HBV status
timeFrame: 0-5 years after birth
measure: Children serum biochemistry
timeFrame: 0-5 years after birth
measure: Maternal HBeAg seroconversion rate
timeFrame: delivery to 5 years after delivery
measure: Maternal ALT elevation
timeFrame: delivery to 5 years after delivery
measure: Maternal HBV DNA
timeFrame: delivery to 5 years after delivery
measure: Children bone growth
timeFrame: 2-5 years after birth
Other outcomes:
Locations:
city: Taipei
country: Taiwan
facility: National Taiwan University Hospital
Study officials:
affiliation: National Taiwan University
name: Mei-Hwei Chang, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Wen WH, Chen HL, Shih TT, Wu JF, Ni YH, Lee CN, Zhao LL, Lai MW, Mu SC, Tung YC, Hsu HY, Chang MH; Taiwan Study Group for the Prevention of Mother-to-Infant Transmission of HBV (PreMIT study)(double dagger). Long-term growth and bone development in children of HBV-infected mothers with and without fetal exposure to tenofovir disoproxil fumarate. J Hepatol. 2020 Jun;72(6):1082-1087. doi: 10.1016/j.jhep.2020.01.021. Epub 2020 Feb 8.
citation: Chang KC, Chang MH, Lee CN, Chang CH, Wu JF, Ni YH, Wen WH, Shyu MK, Lai MW, Chen SM, Hu JJ, Lin HH, Hsu JJ, Mu SC, Lin YC, Liu CJ, Chen DS, Lin LH, Chen HL; Taiwan Study Group for the Prevention of Mother-to-Infant Transmission of HBV (PreMIT study). Decreased neonatal hepatitis B virus (HBV) viremia by maternal tenofovir treatment predicts reduced chronic HBV infection in children born to highly viremic mothers. Aliment Pharmacol Ther. 2019 Aug;50(3):306-316. doi: 10.1111/apt.15321. Epub 2019 Jul 4.