The Safety of Anti-viral Therapy in Preventing HBV MTCT in Pregnant Women After Discontinuation
2018年8月27日 更新者：Chao-Shuang Lin、Third Affiliated Hospital, Sun Yat-Sen University
The Safety of Anti-viral Therapy in Preventing Mother-to-child Transmission of Hepatitis B Virus in Pregnant Women After Discontinuation
Mother-to-child transmission (MTCT) is the most common mode of perpetuating chronic hepatitis B virus (HBV) infection in endemic countries.
Many studies have demonstrated antepartum anti-viral therapy (AVT) is a advisable option to reduce mother-to-child transmission and the risk of vaccination breakthrough in infants who received passive-active immunoprophylaxis.
However, several controversies over antiviral treatment have not been resolved, that is, optimal duration, effect of postpartum therapy, and risk of postpartum alanine aminotransferase (ALT) flare after withdrawal.
Will the risk of postpartum hepatitis flares increase after short-term AVT in late pregnancy for maternal HBV infection is discontinued?
Is there any correlation between postpartum hepatitis flares and withdrawal time?
Will the proportion of postpartum flares be reduced if extending the duration of AVT after delivery?
There is an urgent need in this area.
This study mainly investigated the safety of antiviral therapy in preventing HBV mother-to-child transmission in pregnant women after discontinuation.
研究概览
详细说明
Between June 2015 and December 2017, 111 mothers were enrolled during their visit to the Department of Gynecology and Obstetrics or the Department of Infectious Diseases of the Third Affiliated Hospital of Sun Yat-Sen University in Guangzhou, Guangdong province, China.
Pregnant women fulfilling the inclusion and exclusion criteria were offered participation in the study.
All pregnant women who opted for AVT need to sign a consent form and started on oral telbivudine (LDT) 600 mg or tenofovir disoproxil fumarate (TDF) 300 mg (as per patients' wishes) daily between gestational weeks 24 and 28.
Serum levels of HBV DNA, HBsAg, HBsAb, HBeAg, HBeAb, liver function tests, haematology and renal biochemistry were measured at baseline(i.e. at screening), every 4 weeks after treatment begins, at the time of delivery, and at 1, 2, 3, 6, 12 month postpartum.
After delivery, treatment with LDT or TDF was immediately withdrew to the patients with an intention of breastfeeding, while the other patients, without desire of breastfeeding, would subsequently extend antiviral treatment duration to postpartum 6 weeks.
All infants were vaccinated with genetically engineered HBV vaccine 20 ug according to a standard vaccination regimen (i.e.
within 12h of birth, at week 4 and at week 24) and 200 IU doses of hepatitis B immunoglobulin immediately (within 2h) after birth and at day 15.
The infant's HBV serologic status and HBV DNA were tested at birth (before immunization) and again at 7 months.
The investigators discussed the postpartum liver function after withdrawal and evaluated the impact of extending the postpartum duration of AVT administered for the prevention of perinatal transmission.
研究类型
介入性
注册 (实际的)
111
阶段
- 第四阶段
参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 45年 (成人)
接受健康志愿者
不
有资格学习的性别
女性
描述
Inclusion Criteria:
- Gestational age between 24 and 28 weeks
- Detectable serum HBsAg at the Screening visit and at least 6 months prior
- Serum HBV DNA level >1,000,000 IU/mL at Screening visit
- Alanine aminotransferase (ALT) below the upper limit of normal (ULN; 40 IU/mL)
Exclusion Criteria:
- Patient is co-infected with hepatitis A virus, hepatitis C virus, hepatitis delta virus, hepatitis E virus or HIV.
- Patient has a history of antiviral treatment or concurrent treatment with immunomodulators, cytotoxic drugs, or steroids.
- Patient has clinical signs of threatened miscarriage in early pregnancy.
- Patient has evidence of hepatocellular carcinoma or cirrhosis.
- Patient has evidence of fetal deformity by 3-dimensional ultrasound examination.
- Patient has a husband infected with HBV.
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：预防
- 分配：非随机化
- 介入模型：并行分配
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
|
实验性的：Early cessation
Pregnant mothers who opted for antiviral therapy would start on oral LDT 600 mg or TDF 300 mg (as per patients' wishes) daily between gestational weeks 24 and 28.
Antiviral therapy was discontinued in intrapartum.
|
Pregnant mothers who opted for antiviral therapy would start on oral LDT 600 mg daily between gestational weeks 24 and 28.
其他名称：
Pregnant mothers who opted for antiviral therapy would start on oral TDF 300 mg daily between gestational weeks 24 and 28.
其他名称：
|
|
实验性的：Late cessation
Pregnant mothers who opted for antiviral therapy would start on oral LDT 600 mg or TDF 300 mg (as per patients' wishes) daily between gestational weeks 24 and 28.
After delivery, mothers ceased antiviral treatment at postpartum 6 weeks.
|
Pregnant mothers who opted for antiviral therapy would start on oral LDT 600 mg daily between gestational weeks 24 and 28.
其他名称：
Pregnant mothers who opted for antiviral therapy would start on oral TDF 300 mg daily between gestational weeks 24 and 28.
其他名称：
|
|
无干预：Control
Eligible patients who refused antiviral therapy but consented to the study were assigned to the control arm.
|
研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Postpartum flare incidence
大体时间：From baseline to postpartum 12 months.
|
Time-to-event measures.
Postpartum flare was defined as an alanine aminotransferase (ALT) rise to three times baseline level or five times ULN (40U/L) within 12 months post-delivery.
Maternal would be recorded if postpartum flare occured.
At the end of postpartum 12-month follow-up period, postpartum flare incidence was measured.
|
From baseline to postpartum 12 months.
|
次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
|
Time of flare onset
大体时间：Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.
|
Time-to-event measures.
Time of the onset of postpartum liver damage.
|
Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.
|
|
Proportion of severe flares
大体时间：Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.
|
As per protocol, ALT flares (>5 times baseline level or >10 times ULN) were considered severe adverse events (SAEs).
|
Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.
|
|
Peak ALT during flare
大体时间：Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.
|
Peak ALT during postpartum flare.
|
Baseline (i.e. at screening); at the time of delivery; at 1,2,3,6,12 month postpartum.
|
|
The rate of perinatal transmission
大体时间：7 months after birth.
|
Perinatal transmission was established by detectable HBV DNA and HBsAg levels in the peripheral blood of infants at 7 months.
|
7 months after birth.
|
|
HBV kinetics in patients
大体时间：Baseline (i.e. at screening); at 4-week intervals after treatment was begun up to delivery; at the time of delivery; at 1,2,3,6,12 month postpartum.
|
Changes of HBV viral load in patients treated and not treated with antiviral agents.
|
Baseline (i.e. at screening); at 4-week intervals after treatment was begun up to delivery; at the time of delivery; at 1,2,3,6,12 month postpartum.
|
|
The liver function normalization rate
大体时间：Baseline (i.e. at screening); at 4-week intervals after treatment was begun up to delivery; at the time of delivery; at 1,2,3,6,12 month postpartum.
|
Normal liver function was defined as the value of ALT level lower 40U/L.
|
Baseline (i.e. at screening); at 4-week intervals after treatment was begun up to delivery; at the time of delivery; at 1,2,3,6,12 month postpartum.
|
|
Maternal HBsAg loss/seroconversion rate
大体时间：Baseline (i.e. at screening); at 4-week intervals after treatment was begun up to delivery; at the time of delivery; at 1,2,3,6,12 month postpartum.
|
Measurement of the proportion of maternal hepatitis B surface antigen loss and seroconversion.
|
Baseline (i.e. at screening); at 4-week intervals after treatment was begun up to delivery; at the time of delivery; at 1,2,3,6,12 month postpartum.
|
|
Incidence of perinatal and partum complications
大体时间：Baseline (i.e. at screening); at 4-week intervals after treatment was begun up to delivery; at the time of delivery; at 1,2,3,6,12 month postpartum.
|
Perinatal and partum complications included hypertensive disorders in pregnancy, gestational diabetes mellitus, fetal growth retardation, premature delivery, premature rupture of membrane, and postpartum hemorrhage.
|
Baseline (i.e. at screening); at 4-week intervals after treatment was begun up to delivery; at the time of delivery; at 1,2,3,6,12 month postpartum.
|
|
Birth height
大体时间：At the time of delivery.
|
Measurement of infants' height at the time of delivery.
|
At the time of delivery.
|
|
Birth weight
大体时间：At the time of delivery.
|
Measurement of infants' weight at the time of delivery.
|
At the time of delivery.
|
|
Neonate apgar score at 1 minute
大体时间：At 1 minute after birth.
|
Apgar scores of neonates included activity, pulse, grimace, appearance and respiration.
|
At 1 minute after birth.
|
|
Neonate apgar score at 5 minutes
大体时间：At 5 minutes after birth.
|
Apgar scores of neonates included activity, pulse, grimace, appearance and respiration.
|
At 5 minutes after birth.
|
|
Incidence of deformity
大体时间：At the time of delivery; at 1, 7, 12 month postpartum.
|
The incidence of baby deformity was recorded during the postpartum follow-up period.
|
At the time of delivery; at 1, 7, 12 month postpartum.
|
|
Breastfeeding rate
大体时间：At birth, at 1 and 7 month follow-up.
|
Breast feeding status was assessed in all infants during the postpartum follow-up period.
|
At birth, at 1 and 7 month follow-up.
|
合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
调查人员
- 学习椅：Zhi-liang Gao, PhD、Third Affiliated Hospital, Sun Yat-Sen University
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2015年6月1日
初级完成 (实际的)
2017年12月31日
研究完成 (实际的)
2017年12月31日
研究注册日期
首次提交
2018年1月21日
首先提交符合 QC 标准的
2018年3月12日
首次发布 (实际的)
2018年3月19日
研究记录更新
最后更新发布 (实际的)
2018年8月29日
上次提交的符合 QC 标准的更新
2018年8月27日
最后验证
2018年8月1日
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- Safety of anti-viral agents
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
不
IPD 计划说明
Individual participant data (IPD) is not available to other researchers.
药物和器械信息、研究文件
研究美国 FDA 监管的药品
不
研究美国 FDA 监管的设备产品
不
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.
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Telbivudine 600mg的临床试验
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