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

NCT ID: NCT01312012

Last Updated: 2020-11-27

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE4
• Total Enrollment: 120 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-01-31
• Study Completion Date: 2021-12-31

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.

Conditions

Hepatitis B Virus Infection, Pregnancy

Keywords

hepatitis B virus,mother-infant transmission, nucleoside analog,pregnant women

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

antiviral therapy

Intervention Type: DRUG

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)

Control

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

Group Type: NO_INTERVENTION

No interventions assigned to this group

Interventions

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)

Intervention Type: DRUG

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

• Minimum Eligible Age: 20 Years
• Maximum Eligible Age: 40 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

National Taiwan University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Mei-Hwei Chang, PhD

Role: PRINCIPAL_INVESTIGATOR

National Taiwan University

Locations

National Taiwan University Hospital

Taipei, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Mei-Hwei Chang, PhD

Role: CONTACT

Phone: 886-02-23123456

Email: changmh@ntu.edu.tw

Huey-Ling Chen, PhD

Role: CONTACT

Phone: 886-02-23123456

Email: hueyling@ntu.edu.tw

Facility Contacts

Mei-Hwei Chang, PhD

Role: primary

Huey-Ling Chen, PhD

Role: backup

References

Hsu HY, Chen HL, Chiang CL, Lai MW, Mu SC, Wen WH, Cheng SW, Hu JJ, Chang KC, Lee CN, Liu CJ, Wu JF, Ni YH, Chang MH; Taiwan Study Group for the Prevention of Mother-to-Infant Transmission of HBV (PreMIT study). Characterization of Hepatitis B Virus in Tenofovir-Treated and Untreated Chronically Infected Mothers and Their Immunoprophylaxis Failure Infants. Clin Infect Dis. 2023 Feb 8;76(3):e783-e790. doi: 10.1093/cid/ciac539.

Reference Type: DERIVED

PMID: 35789261 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 32044401 (View on PubMed)

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.

Reference Type: DERIVED

PMID: 31271463 (View on PubMed)

Other Identifiers

201010078M, 201507025RINC

Identifier Type: -

Identifier Source: org_study_id