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.

项目概要/摘要 乙型肝炎病毒 (HBV) 感染在非洲孕妇中流行，但大多数妇女没有症状 并且不知道他们的婴儿处于危险之中。百分之九十出生时感染的婴儿会发展为慢性乙型肝炎 具有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 年消除乙肝病毒的目标，但非洲目前的围产期预防措施还很有限 不足。这是降低人口疾病患病率的一个关键障碍。从出生起就接种乙肝疫苗 75-95% 有效率，但设施交付率低和疫苗冷链要求阻碍了这一成功 单管齐下。非洲大多数接触 HBV 的婴儿在 2-3 个月大时接种第一次 HBV 疫苗 错过了围产期预防窗口。为了解决这个紧迫的问题，这个 R01 应用程序描述了 考虑到潜在功效，推进围产期乙型肝炎预防所需的科学知识存在差距 替诺福韦疗法降低 HBV 病毒载量基于两项在亚洲发表的随机试验以及潜在的 拉米夫定在新生儿预防中的作用。该提案的中心目标是确定一种新颖的干预措施 在非洲预防围产期乙型肝炎病毒传播方面是有效、安全和务实的。这是开发于 对 PA-18-031 中引用的 NICHD 优先事项的响应。为了实现这一目标，一项名为 “REVERT-B：减少非洲乙型肝炎的垂直传播”旨在由 阿拉巴马大学伯明翰分校 (UAB) 的协作、高效且经验丰富的研究团队 在喀麦隆。它将检验以下假设：孕产妇和新生儿抗病毒预防显着减少 与优化护理标准（4 剂）相比，非洲高危女性中的 HBV 垂直传播 从出生时就开始接种乙肝疫苗）。该假设将通过追求两个共同的主要目标得到有效检验 采用析因试验设计。在目标 1 中，将在四个产前进行一项随机、安慰剂对照试验 喀麦隆诊所测试替诺福韦对 480 名 HBV 孕妇减少围产期感染的功效 传播。女性将被随机分配每日服用替诺福韦或安慰剂，并具有优化标准的背景 护理（婴儿疫苗接种）。在目标 2 中，新生儿将被随机分配口服拉米夫定或安慰剂，为期六周 测试新生儿预防的效果。这两个目标的主要终点都是定义的围产期传播 6 个月时患有活动性 HBV 感染 (HBsAg+) 的婴儿比例。子目标将评估 预防和药物依从性的安全性。该 III 期试验的数据将用于支持后续行动 测试孕产妇和/或新生儿抗病毒预防联合治疗的有效性和可行性的研究 对资源有限环境中孕妇的多国研究。预期结果是扩大 为患有 HBV 的孕妇提供科学工具包（类似于围产期 HIV 预防）并推动 消除全球围产期乙肝病毒传播的长期目标。