Tenofovir in Late Pregnancy to Prevent Vertical Transmission of Hepatitis B Virus

New Discovery LLC200 enrolled

Overview

Immunoprophylaxis failure of hepatitis B virus (HBV) leading to vertical transmission remains a concern and has been reported in approximately 8-15% of infants born to hepatitis B e antigen (HBeAg) positive mothers with high levels of HBV DNA. Maternal HBV DNA \> 6log10 copies/mL (or \>200,000 IU/mL) is the major risk for the mother-to-child transmission. Prior observational studies have shown that antiviral therapy including lamivudine or telbivudine use during late pregnancy can safely reduce the rate of vertical transmission in this special population compared to untreated patients. Tenofovir Disoproxil (TDF), a pregnancy category B medication, reduces HBV DNA and normalizes serum alanine aminotransferase (ALT) in chronic hepatitis B patients (CHB) with few adverse effects. Two aspects on tenofovir use in pregnancy will be evaluated prospectively in this study: 1. The data on its tolerability and safety in HBeAg+ pregnant women with HBV DNA \> 6log10 copies/mL (or \> 200,000 IU/mL) during late pregnancy and infants. 2. Its efficacy in the reduction of HBV vertical transmission rate.

Eligible mothers will be randomized (1:1) to either TDF-treated group or untreated group with about 100 subjects in each arm. The treatment group will receive TDF starting at week 30-32 of gestation until week 4 postpartum; follow up will continue until post-partum week 28 and infants age of 28 weeks. Untreated group will receive the standard of care with similar follow-up schedule as the treatment group.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

NONE

Enrollment

200

Conditions

Eligibility

Sex: FEMALEMin age: 20 YearsMax age: 35 Years

Medical Language ↔ Plain English

Inclusion Criteria: * documented CHB infection with HBsAg positive \> 6 months * HBeAg+ CHB pregnant women * gestational age between 30-32 weeks * HBV DNA \> 6 log10 copies/mL (or \>200,000 IU/mL) * both mother and father of the child are willing to consent for the study Major Exclusion Criteria: * co-infection with hepatitis A, C, D, E, HIV-1 or sexually transmitted disease (STD) * decompensated liver disease or significant co-morbidity * history of abortion, or diagnosis of fetal defect, or congenital malformation in prior pregnancy * antiviral used within six months prior to this pregnancy, or history of renal or tubular function impairment due to adefovir. * requirement for other medication during pregnancy to manage other chronic disease(s) or concurrent treatment with immune-modulators, cytotoxic drugs, or steroids * the biological father of the child had CHB * clinical signs of threatened miscarriage in early pregnancy * evidence of hepatocellular carcinoma * maternal alanine aminotransferase (ALT) \> or = 5 x upper limit of normal (U/mL), or Total Bilirubin \> or = 2, or glomerular filtration rate (GFR) \< 100, or Albumin \< 25 g/L * evidence of fetal deformity by ultrasound examination * patient is participating other clinical study

Locations (5)

Southwest Hospital

Chongqing, Chongqing Municipality, China

The Fifth Hospital of Shijiazhuang

Shijiazhuang, Hebei, China

Nanyang Central Hospital

Nanyang, Henan, China

The Second Affiliated Hospital of the Southeast University

Nanjing, Jiangsu, China

Hepatobiliary Disease Hospital of Jilin Province

Changchun, Jilin, China

Outcomes

Primary Outcomes

Measure the number of infants who have HBV infection at the age of 28 weeks

Time frame: From the date of birth to age of 28 weeks

Assessment of the safety and tolerability of TDF, measure the number of participants and paired infants with adverse events

Time frame: From the date of randomization until 28 weeks of postpartum.

Secondary Outcomes

Measure maternal HBV DNA reduction during the study period when compared to the baseline

Time frame: From the date of radomization to the time of delivery (upto 12 weeks from the radomization)