Safety and Efficacy of Tenofovir Alafenamide to Prevent Mother-to-child Transmission of Hepatitis B Virus in Middle/Late Pregnancies With High Hepatitis B Virus DNA Load: A Prospective Multicenter Cohort Study
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 发起方
- 入组人数
- 200
- 试验地点
- 2
- 主要终点
- The proportion of interrupting MTCT
研究概览
简要总结
Mother-to-child transmission (MTCT) is still the main transmission route of HBV in high-endemic areas, such as China, sub-Saharan Africa, etc. Some infants born of mothers with high HBV DNA load (≥2×10^5 IU/ml) are still infected with HBV even if these infants receive the combined immunization on time. Therefore, guidelines including AASLD and EASL recommend that pregnant women with high HBV DNA load should take antiviral drugs (tenofovir disoproxil fumarate or telbivudine) to reduce MTCT of HBV from gestation 24-28 weeks.
However, side effects of TDF on infants are reported. For example, neutropenia and the decrease of bone mineral density are found in early age infants who are ever exposed to TDF during their fetal life.
Tenofovir alafenamide (TAF), a new prodrug of tenofovir (TFV), has a higher antiviral potency, a higher peripheral blood mononuclear cell (PBMC) intracellular tenofovir diphosphate (TFV pp) level and a lower plasma TFV concentration. As the successor of TDF, the dose of TAF that is took orally every day is approximately 1/10 of TDF. TAF has a much lower risk of kidney toxicity and has almost no effect on the bone mineral density. TAF has been approved and recommended as the first-line drug to treat patients with chronic hepatitis B (CHB) by AASLD, EASL, etc. However, there are relatively few data of TAF on pregnancies with high HBV DNA load. It is urgently to clarify the safety and efficacy of TAF on interrupting MTCT of HBV in pregnancies with high HBV DNA load.
In the present study, the investigators enroll middle/late pregnancies with high HBV DNA load(≥2×10^5 IU/ml). The participants are randomly divided into two groups. Then the participants are treated with TAF or TDF respectively. All enrolled participants are followed-up for 2 years. Objectives of the present study are as follows:
A. To clarify safety and efficacy of TAF on interrupting MTCT of HBV in middle/late pregnancies with high HBV DNA load.
B. To clarify effects of TAF on obstetric complications in middle/late pregnancies with CHB.
C. To clarify effects of TAF on birth defects of infants born in mothers with CHB.
D. To clarify the change of virology and biochemistry indexes in women with CHB during pregnancy and postpartum.
E. To clarify effects of TAF treatment on participants. F. To clarify growth parameters of the infants exposed to TAF during their fetal life.
G. To clarify the pharmacokinetics of TAF in pregnant populations.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 20 Years 至 40 Years（Adult）
- 性别
- Female
- 接受健康志愿者
- 否
入选标准
- •Age of 20-40 years.
- •Positive for HBsAg ≥6 months.
- •HBV DNA load of ≥ 2×10^5 IU/ml.
- •Gestation 24-28 weeks .
- •Pregnancies are orally administrated with TAF (25mg/day) or TDF (300mg/day) from 24-28 weeks of gestation.
- •The good compliance of patients.
排除标准
- •Patients with antibodies against HIV, HCV, HDV, or other forms of chronic liver disease.
- •Evidence of hepatocellular carcinoma, decompensated liver disease, auto-immune hepatitis, or significant renal, cardiovascular, respiratory or neurological comorbidity.
- •Concurrent treatment with nephrotoxic drugs, glucocorticoids, cytotoxic drugs, nonsteroidal anti-inflammatory drugs, or immune modulators.
- •Ultra-sonographic evidence of fetal deformity, abnormal fetal development or placental abnormality.
- •Clinical signs of threatened miscarriage.
- •History of complication of pregnancy.
- •History of nucleoside analogues (NA) treatment.
研究组 & 干预措施
TAF group
Patients who take TAF during pregnancy.
TDF group
Patients who take TDF during pregnancy.
结局指标
主要结局
The proportion of interrupting MTCT
时间窗: During 7-12 months after birth
The proportion of HBV infection in the infants at 1 year of age. Testing for HBsAg in the infants between 7 and 12 months of age.
ALT levels in pregnancies
时间窗: After enrollment and up to delivery
ALT levels are measured every month during pregnancy.
HBeAg conversion rate in pregnancies
时间窗: After enrollment and up to delivery
HBeAg is measured every 6 months during pregnancy.
HBV DNA load in pregnancies
时间窗: After enrollment and up to delivery
HBV DNA load is measured during 24-28 weeks of gestation and at birth, respectively.
次要结局
- The proportion of birth defects in the infants at 1 month age.(Up to 1 month after birth)
- Liver function of women with CHB(Up to 2 years after delivery)
- The blood drug concentration of TAF in pregnancies(Day 5 up to day 40 after the administration of TAF)
- Head circumferences of infants(Once a year up to 3 years old after birth)
- Denver Developmental Screening Test of infants(Once a year up to 3 years after birth)
- Mode of delivery.(At the time of delivery)
- Weights of infants(Once a year up to 3 years after birth)
- HBV DNA load in postpartum mothers(Up to 2 years after delivery)
- Heights of the infants(Once a year up to 3 years after birth)
- ALT levels in postpartum mothers(Up to 2 years after delivery)
- HBeAg conversion rate in postpartum mothers(Up to 2 years after delivery)
- Liver ultrasound test of women with CHB(Up to 2 years after delivery)
研究者
Xingfei Pan
Director of Department of Infectious Diseases
The Third Affiliated Hospital of Guangzhou Medical University