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）

基本信息

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
项目类别：
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

项目摘要

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有 90% 出生时感染的婴儿会患上慢性乙型肝炎。感染后出现疾病的晚期表现，包括肝硬化和肝细胞癌。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这是降低人群出生后乙型肝炎疫苗接种率的一个关键障碍。 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非洲大多数接触乙肝病毒的婴儿在 2-3 个月大时接受第一次乙肝疫苗接种。为了解决这个紧迫的问题，这个 R01 应用程序描述了错过围产期预防窗口的情况。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该提案的中心目标是确定一种新的干预措施，该干预措施可用于新生儿拉米夫定预防。在非洲预防围产期乙型肝炎病毒传播是有效、安全和务实的。响应 PA-18-031 中提到的 NICHD 优先事项，为了实现这一目标，开展了一项名为“创新”的多中心临床试验。 “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它将检验孕产妇和新生儿抗病毒预防显着减少的假设。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）这一假设将通过追求两个共同的主要目标得到有效检验。在目标 1 中，将在四个产前进行随机、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女性将被随机分配每日服用替诺福韦或安慰剂，并以优化标准为背景。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。测试新生儿预防的有效性，这两个目标的主要终点都是围产期传播。子目标将评估 6 个月大时患有活动性 HBV 感染 (HBsAg+) 的婴儿比例。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下的孕妇进行的一项多国研究的预期结果是扩大研究范围。为感染 HBV 的孕妇提供科学工具包（类似于围产期 HIV 预防）并推进消除全球围产期乙肝病毒传播的长期目标。