Chronic Infection, Hepatitis B Infection, Viremia
Conditions
Keywords
Hepatitis B, Vertical transmission, Pregnancy, Antiviral treatment
Brief summary
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.
Detailed description
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.
Interventions
DRUGTDF treatment
About 100 mothers treated with tenofovir from 30-32 weeks of pregnancy to the week 4 of postpartum, then observed to the end of the study at post-partum week 28, paired infants received standard HBV prophylaxis.
Sponsors
Gilead Sciences
New Discovery LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
20 Years to 35 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Measure the number of infants who have HBV infection at the age of 28 weeks | 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 | From the date of randomization until 28 weeks of postpartum. |
Secondary
| Measure | Time frame |
|---|---|
| Measure maternal HBV DNA reduction during the study period when compared to the baseline | From the date of radomization to the time of delivery (upto 12 weeks from the radomization) |
| percentage of mothers with sero-negativity or sero-conversion of HBsAg and/or HBeAg in each group for comparison | From the date of randomization until 28 weeks of postpartum. |
Countries
China
Outcome results
None listed