Antiviral prophylaxis to prevent perinatal transmission of HBV in Thailand

泰国抗病毒预防措施预防围产期乙型肝炎病毒传播

• 批准号: 8538341
• 负责人: Gonzague Joseph Jourdain
• 金额: $ 45.77万
• 依托单位: INSTITUTE OF RESEARCH AND DEVELOPMENT
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-09-01 至 2016-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8538341
• 关键词: Active Immunization; Acute; Adult; Alanine Transaminase; American; Antigens; Antiviral Agents; Antiviral Therapy; Asia; Asians; Birth; Cancer Etiology; Cause of Death; Cessation of life; Child; Childhood; Chronic; Chronic Hepatitis B; Cirrhosis; Country; Detection; Disease; Double-Blind Method; Effectiveness; Enrollment; Epidemic; European; Flare; Goals; Guidelines; HIV; Hepatitis; Hepatitis B; Hepatitis B Surface Antigens; Hepatitis B Transmission; Hepatitis B Vaccination; Hepatitis B Vaccines; Hepatitis B Virus; Hepatitis B e Antigens; High Risk Woman; Immune; Immunization Programs; Immunoglobulins; Infant; Infection; Institute of Medicine (U.S.); Intervention; Lamivudine; Letters; Life; Liver; Liver Function Tests; Liver diseases; Malignant neoplasm of liver; Mothers; Neonatal; Outcome; Passive Immunization; Perinatal; Pharmaceutical Preparations; Phase; Placebo Control; Placebos; Policies; Postpartum Period; Practice Guidelines; Pregnancy; Pregnant Women; Prevalence; Prevention; Primary carcinoma of the liver cells; Prophylactic treatment; Public Health; Randomized; Randomized Clinical Trials; Recommendation; Risk; Risk Assessment; Safety; Site; Societies; Surface Antigens; Tenofovir; Tenofovir disoproxil fumarate; Testing; Thailand; Third Pregnancy Trimester; United States National Institutes of Health; Vaccination; Vertical Disease Transmission; Viral Load result; Virus; Virus Diseases; Virus Replication; Woman; anti-hepatitis B; comparative efficacy; discontinuation trial; experience; immunoprophylaxis; improved; in utero; intrapartum; liver injury; passive immunoprophylaxis; prevent; transmission process; viral DNA

DESCRIPTION (provided by applicant): The proposed study is a phase III, multicenter, controlled, double blind, randomized clinical trial in Thailand to compare the efficacy, safety and tolerance of each of two drugs, tenofovir and lamivudine, versus placebo, given to hepatitis B (HB) chronically infected pregnant women with a positive HBeAg test and normal liver function tests, from 28 weeks' gestation until two months postpartum to prevent perinatal transmission of hepatitis B virus (HBV). Chronic HBV, complicated by cirrhosis and hepatocellular carcinoma (HCC), is the 10th leading cause of death worldwide. About 7% of Thai adults are HBsAg carriers. Universal immunization programs have dramatically reduced the prevalence of infection wherever they have been implemented. Infant HBV immunization and HB immunoglobulin administered at birth effectively prevent most transmission from HBV infected mothers but, despite this active and passive immunization, about 12% of HBV highly viremic mothers transmit the virus to their infants. The antigen HBe (HBeAg) is a marker of high replication. Studies have suggested that antiviral treatment at the end of pregnancy and in the postpartum can reduce the risk of transmission to the child. A potential limitation to this approach is the risk of hepatic disease exacerbation (flare) following discontinuation of antiviral treatment, which has not been properly evaluated. No randomized clinical trials have adequately demonstrated the efficacy and safety of antiviral treatment and this approach is not recommended by the Associations for the Study of Liver Diseases. We hypothesize that tenofovir or lamivudine can decrease HBV viral load in HBV infected pregnant women and therefore the risk of in utero, intrapartum and postpartum transmission before infants are protected by passive-active immunization. We also hypothesize that only moderate flares will be observed after discontinuation of a short antiviral course (5 months). While the primary objective of the study is to assess the efficacy of tenofovir or lamivudine versus placebo for the prevention of perinatal transmission, an important secondary objective is the assessment of the risk of postpartum hepatic disease exacerbation. HBsAg positive women will be enrolled if they have an HBeAg positive test and ALT 30 U/L. They will be randomized to receive tenofovir or lamivudine or placebo from 28 weeks of pregnancy until 2 months postpartum. Within 2 years, 588 women and their infants will be enrolled in 8 sites of the PHPT network in Thailand, where the teams have gained considerable experience in conducting trials for the prevention of mother to child transmission of HIV over the past 15 years. Mothers and infants will be followed until one year postpartum. The primary endpoint will be the detection of HBsAg and HBV DNA at six months of life. An interim analysis will be conducted when half of the outcomes are available. The results of the study will help define policy to manage HBV infected pregnant women to prevent perinatal transmission.

描述（由申请人提供）：拟议的研究是泰国的III期，多中心，受控的，双盲，随机临床试验，以比较疗效，安全性和 对丙型肝炎（HB）持续感染的两种药物（替诺福韦和安慰剂）的耐受性，与安慰剂相对于安慰剂，持续感染了HBEAG阳性测试和正常肝功能测试，从28周的妊娠到产后两个月，以防止产后两个月丙型肝炎病毒（HBV）。慢性HBV因肝硬化和肝细胞癌（HCC）而复杂化，是全世界死亡的第十个主要原因。大约7％的泰国成年人是HBSAG载体。无论何处，通用免疫计划都大大降低了感染的流行。婴儿HBV免疫和出生时给药的HB免疫球蛋白有效地防止了HBV感染的母亲的大多数传播，但是，尽管采用了这种主动和被动的免疫，但大约12％的HBV高度病毒性母亲将病毒传播给婴儿。抗原HBE（HBEAG）是高复制的标记。研究表明，妊娠结束时和产后抗病毒药物可以降低向儿童传播的风险。这种方法的潜在局限性是抗病毒后肝病加剧（耀斑）的风险 治疗，尚未正确评估。没有足够的随机临床试验证明了抗病毒药物治疗的功效和安全性，并且不建议该方法进行肝病研究。我们假设Tenofovir或Lamivudine可以减少HBV感染孕妇的HBV病毒载量，因此在婴儿受到被动免疫保护的保护之前，在子宫内，肠内和产后传播的风险。我们还假设在停止短暂的抗病毒病程（5个月）后，只会观察到适度的耀斑。该研究的主要目的是评估替诺福韦或拉米夫定与安慰剂对预防的功效 围产期传播的一个重要的次要目标是评估产后肝病加剧的风险。如果HBSAG阳性妇女的HBEAG阳性测试和Alt 30 U/L，则将入学。从怀孕的28周到产后2个月，他们将被随机接收替诺福韦，拉米夫丁或安慰剂。在2年内，将有588名妇女及其婴儿在泰国的PHPT网络的8个地点中注册，在过去的15年中，团队在进行预防母亲传播HIV的试验方面获得了丰富的经验。母亲和婴儿将被遵循，直到产后一年。主要终点是在六个月生命的六个月内检测HBSAG和HBV DNA。当有一半的结果可用时，将进行临时分析。该研究的结果将有助于定义管理HBV感染孕妇以防止围产期传播的政策。