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: 10375537
• 负责人: Jodie Ann Dionne
• 金额: $ 40.35万
• 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/10375537
• 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; Enrollment; Equipoise; Flare; Follow-Up Studies; Fumarates; Goals; Guidelines; Gynecology; HIV; Health; Hepatitis B; Hepatitis B Infection; 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; Prophylactic treatment; Publishing; Randomized; Randomized Controlled Trials; Recommendation; Reporting; Research; Research Design; Resource-limited setting; Risk; 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; Viral Load result; Virus Diseases; Woman; World Health Organization; arm; base; 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; standard care; standard of care; success; 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/文摘