Tenofovir Disoproxil Fumarate in Late Pregnancy to Prevent Vertical Transmission of Hepatitis B Virus in Highly Viremic Mothers
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 200
- 试验地点
- 5
- 主要终点
- Measure the number of infants who have HBV infection at the age of 28 weeks
研究概览
简要总结
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:
- 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.
- Its efficacy in the reduction of HBV vertical transmission rate.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
入排标准
- 年龄范围
- 20 Years 至 35 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
TDF treatment arm
tenofovir from 30-32 weeks of pregnancy to the week 4 of postpartum for mothers and standard immunoprophylaxis to their infants
干预措施: TDF treatment (Drug)
结局指标
主要结局
Measure the number of infants who have HBV infection at the age of 28 weeks
时间窗: 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
时间窗: From the date of randomization until 28 weeks of postpartum.
次要结局
- 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.)
- Measure maternal HBV DNA reduction during the study period when compared to the baseline(From the date of radomization to the time of delivery (about 8 - 10 weeks from the radomization))