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.

项目总结/摘要 B型肝炎病毒（HBV）感染在非洲孕妇中流行，但大多数妇女无症状 却不知道自己的孩子有危险出生时感染的婴儿中有90%会发展成慢性HBV 感染，晚期表现为疾病，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，但非洲目前的围产期预防措施 不足这是降低人口疾病流行率的一个关键障碍。从出生开始接种乙肝疫苗是 75-95%有效，但设施交付率低和疫苗冷链要求阻碍了这一成功 one pronged管弦乐approach方法.非洲大多数接触HBV的婴儿在2-3个月大时接受第一次HBV疫苗接种 错过了围产期预防窗口期为了解决这个紧迫的问题，此R 01应用程序描述了 考虑到以下因素的潜在疗效，推进围产期HBV预防所需的科学知识存在差距： 基于两项已发表的亚洲随机试验和一项潜在的 拉米夫定对新生儿的预防作用。该提案的中心目标是确定一种新的干预措施， 在非洲预防HBV的围产期传播是有效、安全和实用的。这是在 响应PA-18-031中引用的NICHD优先事项。为了实现这一目标，一项创新的多中心临床试验， “REVERT-B：减少非洲B型肝炎的垂直传播”旨在由一个 伯明翰亚拉巴马大学（UAB）的合作，富有成效和经验丰富的研究团队， 在喀麦隆。它将检验这样一个假设，即母亲和新生儿的抗病毒预防可以显著降低 与最佳护理标准（4剂）相比，非洲高危妇女中HBV垂直传播 乙肝疫苗从出生时就开始接种。通过追求两个共同的主要目标， 采用析因试验设计。在目标1中，将在4个产前检查中进行随机、安慰剂对照试验。 在喀麦隆的一家诊所，测试替诺福韦在480名乙型肝炎孕妇中减少围产期死亡率的疗效。 传输妇女将被随机分配到每日替诺福韦或安慰剂与优化标准的背景 婴儿疫苗（Infant Vaccination）在目标2中，新生儿将随机接受口服拉米夫定或安慰剂治疗6周 来测试新生儿预防的效果这两个目标的主要终点是围产期传播定义 以6个月龄时活动性HBV感染（HBsAg+）婴儿的比例表示。次级目标将评估 预防和药物依从性的安全性。本III期试验的数据将用于支持随访 研究，以测试联合母亲和/或新生儿抗病毒预防的有效性和可行性， 对资源有限环境中的孕妇进行的多国研究。预期的结果是扩大 为HBV感染孕妇提供科学工具包（类似于围产期艾滋病毒预防）， 长期目标是在全球范围内消除围产期HBV传播。