Reducing Vertical Transmission of Hepatitis B in Africa (REVERT-B Trial)

减少非洲乙型肝炎的垂直传播（REVERT-B 试验）

• 批准号: 10612859
• 负责人: Jodie Ann Dionne
• 金额: $ 39.66万
• 依托单位: UNIVERSITY OF ALABAMA AT BIRMINGHAM
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-05-18 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10612859
• 关键词: AIDS prevention; Address; Adherence; Adverse event; Africa; Africa South of the Sahara; Age Months; Alabama; American; Antigens; Antiviral Agents; Asia; Birth; Breast Feeding; Cameroon; China; Chronic Hepatitis B; Cirrhosis; Clinic; Clinical Trials Design; Cold Chains; Conduct Clinical Trials; Country; Data; Decision Modeling; Diphtheria-Tetanus-Pertussis Vaccine; Discipline of obstetrics; Disease; Dose; Effectiveness; Eligibility Determination; Enrollment; Equipoise; Flare; Follow-Up Studies; Fumarates; Goals; Guidelines; Gynecology; HIV; Health; Hepatitis B; Hepatitis B Infection; Hepatitis B Surface Antigens; Hepatitis B Transmission; Hepatitis B Vaccination; Hepatitis B Vaccines; Hepatitis B Virus; High Risk Woman; Immunoglobulins; Infant; Infection; Infection prevention; Intervention; Knowledge; Lamivudine; Liver diseases; Maternal and Child Health; Maternal-fetal medicine; Measures; Mother-to-child HIV transmission; Multi-Institutional Clinical Trial; National Institute of Child Health and Human Development; Neonatal; Newborn Infant; Oral; Outcome; Perinatal; Perinatal Infection; Perinatal transmission; Pharmaceutical Preparations; Pharmacy facility; Placebos; Policies; Population; Postpartum Period; Pregnancy; Pregnant Women; Prevalence; Prevention; Primary carcinoma of the liver cells; Productivity; Prophylactic treatment; Publishing; Randomized; Randomized, Controlled Trials; Recommendation; Reporting; Research; Research Design; Resource-limited setting; Risk; Risk Reduction; Role; Safety; Series; Social Values; Societies; Tenofovir; Testing; Thailand; Time; United States; United States National Institutes of Health; Universities; Vaccinated; Vaccination; Vaccines; Vertical Disease Transmission; Vertical Transmission; Viral; Viral Load result; Virus Diseases; Woman; World Health Organization; arm; college; design; effectiveness testing; efficacy testing; experience; high risk; infant infection; infection rate; innovation; medication compliance; neonatal infection; neonate; novel; novel strategies; nucleotide analog; perinatal HIV; perinatal intervention; phase III trial; pregnant; prenatal; prevent; primary endpoint; priority pathogen; randomized placebo controlled trial; randomized trial; response; safety assessment; standard care; standard of care; success; transmission process; treatment as usual; trial design; virus envelope

Project Summary/Abstract Hepatitis B virus (HBV) infection is endemic among pregnant women in Africa yet most women are asymptomatic and unaware that their infants are at risk. Ninety percent of infants infected at birth will develop chronic HBV infection with late manifestations of disease that include cirrhosis and hepatocellular carcinoma. The World Health Organization set a goal of HBV elimination by 2030 but current perinatal prophylaxis in Africa is inadequate. This is a key barrier to reducing the population prevalence of disease. HBV vaccination from birth is 75-95% effective but low facility delivery rates and vaccine cold chain requirements hinder the success of this one-pronged approach. Most HBV-exposed infants in Africa receive their first HBV vaccine at 2-3 months of age which misses the perinatal prevention window. To address this pressing problem, this R01 application describes gaps in scientific knowledge needed to advance perinatal HBV prevention considering the potential efficacy of tenofovir therapy in reducing HBV viral load based on two published randomized trials in Asia and a potential role for neonatal lamivudine prophylaxis. The central goal of this proposal is to identify a novel intervention that is effective, safe and pragmatic in preventing perinatal transmission of HBV in Africa. This was developed in response to NICHD priorities cited in PA-18-031. To meet this goal, an innovative, multicenter clinical trial titled “REVERT-B: Reducing Vertical Transmission of Hepatitis B in Africa” was designed to be carried out by a collaborative, productive and experienced research team at the University of Alabama at Birmingham (UAB) and in Cameroon. It will test the hypothesis that maternal and neonatal antiviral prophylaxis significantly reduces HBV vertical transmission among high-risk women in Africa compared to optimized standard of care (4-dose HBV vaccination beginning at birth). The hypothesis will be efficiently tested by pursuing two co-primary aims with a factorial trial design. In Aim 1, a randomized, placebo-controlled trial will be conducted in four prenatal clinics in Cameroon to test the efficacy of tenofovir in 480 pregnant women with HBV in reducing perinatal transmission. Women will be randomized to daily tenofovir or placebo with a background of optimized standard of care (infant vaccination). In Aim 2, neonates will be randomized to oral lamivudine or placebo for six weeks to test the efficacy of neonatal prophylaxis. The primary endpoint for both aims is perinatal transmission defined as the proportion of infants with active HBV infection (HBsAg+) at 6 months of age. Sub-aims will assess the safety of prophylaxis and medication adherence. Data from this Phase III trial will be used to support follow up studies to test the effectiveness and feasibility of combination maternal and/or neonatal antiviral prophylaxis in a multi-country study of pregnant women in resource-limited settings. The expected outcome is to expand the scientific toolkit for pregnant women with HBV (analogous to perinatal HIV prevention) and advance toward the long-term goal of eliminating perinatal HBV transmission worldwide.

项目摘要/摘要 乙型肝炎病毒（HBV）感染是非洲孕妇的地方性，但大多数妇女无症状 并且不知道自己的婴儿有危险。 90％的婴儿在出生时感染的婴儿将发展慢性HBV 疾病晚期表现的感染，包括肝硬化和肝细胞癌。世界 卫生组织设定了到2030年消除HBV的目标，但目前在非洲的围产期预防是 不足。这是降低疾病流行率的关键障碍。 HBV出生时的疫苗接种是 75-95％有效但设施较低的交付率和疫苗冷链要求阻碍了这一成功 一方面的方法。非洲大多数暴露于HBV的婴儿在2-3个月大时接受其首次HBV疫苗 错过了围产期预防窗口。为了解决此紧迫问题，此R01应用程序说明 考虑到预防围产期HBV所需的科学知识差距，考虑到了潜在的有效性 基于亚洲的两个已发表的随机试验，替诺福韦治疗减少HBV病毒负荷和潜力 新生儿腹膜预防的作用。该提案的核心目标是确定一种新颖的干预措施 在防止非洲的HBV围产期传播方面是有效，安全和务实的。这是在 PA-18-031中引用的NICHD优先级的响应。为了实现这一目标，一项创新的多中心临床试验标题为 “恢复B：减少非洲丙型肝炎的垂直传播”，旨在通过A进行 伯明翰（UAB）的阿拉巴马大学的合作，生产和经验丰富的研究团队和 在喀麦隆。它将检验以下假设：材料和新生儿抗病毒预防可显着降低 与优化的护理标准相比，非洲高风险女​​性的HBV垂直传播（4剂量 HBV疫苗接种从出生开始）。该假设将通过追求两个共同主要目标来有效检验 带有阶乘试验设计。在AIM 1中，将在四个产前进行随机的安慰剂对照试验 喀麦隆的诊所测试480名HBV孕妇替诺福韦的效率 传播。妇女将被随机分配到具有优化标准背景的每日替诺福韦或安慰剂 护理（婴儿疫苗）。在AIM 2中，新生儿将被随机分配到口服lamivudine或安慰剂六个星期 测试新生儿预防的效率。这两个目标的主要终点是定义的围产期传输 作为6个月大的活性HBV感染（HBSAG+）的婴儿的比例。子iams将评估 预防和药物依从性的安全。该阶段III试验的数据将用于支持后续行动 研究结合材料和/或新生儿抗病毒预防的有效性和可行性 在资源有限的环境中对孕妇的多国研究。预期的结果是扩大 HBV孕妇的科学工具包（类似于围产期艾滋病毒的艾滋病毒），并朝着朝向 消除全球围产期HBV传播的长期目标。