Non-inferiority study of adjuvanted vs. high dose flu vaccine in residents of long term care

长期护理居民中佐剂与高剂量流感疫苗的非劣效性研究

• 批准号: 9412645
• 负责人: DAVID H CANADAY
• 金额: $ 79.99万
• 依托单位: CASE WESTERN RESERVE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-12-01 至 2020-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9412645
• 关键词: Adjuvant; Adjuvant Study; Adult; American; Antibodies; Antibody titer measurement; B-Lymphocytes; Biological Assay; Blinded; Blood; Blood specimen; Centers for Disease Control and Prevention (U.S.); Cessation of life; Clinical; Data; Diagnosis; Dose; Effectiveness; Elderly; Enrollment; FDA approved; Future; Guidelines; Head; Hemagglutinin; Hospitalization; Immune; Immunity; Immunologics; Individual; Industry; Infection; Inferior; Influenza; Influenza prevention; Laboratories; Licensure; Long-Term Care; Manufacturer Name; Methods; Neuraminidase; Nursing Homes; Persons; Pneumonia; Population; Randomized Clinical Trials; Research Design; Risk; Sampling; Scheme; Seasons; Serological; Serum; Skilled Nursing Facilities; Surrogate Endpoint; Testing; Time; Uncertainty; Vaccination; Vaccines; Virus; aged; anti-influenza; clinical research site; cohort; comparative efficacy; high risk; human old age (65+); immunogenicity; in vitro Bioassay; influenza virus vaccine; innovation; primary endpoint; protective efficacy; residential care facility; response; seasonal influenza; seroconversion; treatment group

Project Summary / Abstract Influenza and pneumonia are the most common infection-related and vaccine-preventable causes of hospitalization and death. Over 90% of influenza-related deaths occur among the 13% of adults aged >65 years. Over 2 million Americans reside in nursing homes, skilled nursing facilities, or long-term residential care facilities, a number the CDC projects will significantly grow in the coming decades. These seniors rank highest for risk of influenza complications. Two influenza vaccines now available are FDA approved specifically for persons over age 65: the newly approved adjuvanted seasonal influenza vaccine (Fluad®) and the increasingly used high dose (HD(FluzoneHD®)) vaccine approved in 2009. The absolute or relative clinical advantage to long-term care residents of Fluad vs. HD over non-adjuvanted standard dose (SD) vaccine remains unclear from existing immunologic and clinical evidence. Fluad and HD have not been compared head-to-head and an industry-sponsored study is unlikely to be conducted to evaluate relative efficacy or effectiveness due to uncertainty as to whether manufacturers will gain additional market advantage while risking uncovering relative inferiority. Both Fluad and HD vaccine have been shown individually to be more effective than SD vaccine in trials conducted in different cohorts and years. HD vaccine is more expensive than SD vaccine, and Fluad is less expensive than HD vaccine. As an adjuvanted vaccine, Fluad has been shown to have higher levels of heterologous immunity to drifted influenza strains than non-adjuvanted (SD) vaccine - another potential advantage of Fluad over HD vaccine, which is non-adjuvanted. Heterologous immunity is particularly important in bad match years when the CDC's strain choices for vaccine composition in that season are incorrect. Also, adjuvant is used in vaccines in general to maintain higher antibody titers for a longer period of time. This project's rationale and innovation derive from its ability to help determine the best use of these two vaccines in the setting of one of the most vulnerable elderly populations - those living in long-term care (LTC) settings such as nursing homes (NH). Overall the immunogenicity and clinical analyses they propose here are essential to provide support and rationale as to whether an enormously more expensive multi-site clinical endpoint RCT to compare these two vaccines is warranted. Hypothesis: Adjuvanted flu vaccine, Fluad, is not immunologically inferior to HD influenza vaccine in older persons living in long-term care. They propose a non-inferiority randomized clinical trial to enroll 558 NH residents age 65 and older to receive either Fluad or HD vaccine at 1:1 ratio. Blood will be sampled pre- and post-vaccine (1 mo after vaccination) and after the influenza season is over for blinded laboratory analysis. Aim 1. Primary objective: To determine if Fluad is immunologically non-inferior to HD influenza vaccine in NH residents over age 65. Aim 2: Secondary objective: To determine if Fluad has greater heterologous immunity than HD vaccine. Aim 3: Pilot clinical objective: To determine if Fluad has similar protective efficacy to HD vaccine.

项目总结/摘要 流感和肺炎是最常见的感染相关和疫苗可预防的原因， 住院和死亡。超过90%的流感相关死亡发生在13%的65岁以上的成年人中 年超过200万美国人居住在疗养院，专业护理设施或长期住宿护理 设施，一些疾病预防控制中心的项目将显着增长，在未来几十年。这些高年级学生的排名最高 流感并发症的风险。目前有两种流感疫苗已获FDA批准， 65岁以上人群：新批准的季节性流感佐剂疫苗（Fluad®）和 2009年批准的高剂量（HD（FluzoneHD®））疫苗使用率越来越高。绝对或相对临床 Fluad与HD相比，对长期护理居民的优势优于无佐剂标准剂量（SD）疫苗 从现有的免疫学和临床证据来看仍不清楚。未对Fluad和HD进行比较 不太可能进行头对头和行业申办的研究来评价相对疗效，或 由于不确定制造商是否会获得额外的市场优势， 冒着暴露相对劣势的风险 Fluad和HD疫苗在试验中均显示比SD疫苗更有效 在不同的队列和年份进行。HD疫苗比SD疫苗更贵，Fluad更便宜 比HD疫苗更贵。作为佐剂疫苗，Fluad已被证明具有更高水平的 与无佐剂（SD）疫苗相比，对漂移流感病毒株的异源免疫-另一种潜在的 Fluad相对于HD疫苗的优势，后者是无佐剂的。异种免疫尤其重要 当疾病预防控制中心在该季节疫苗组成的菌株选择不正确时，还有， 佐剂通常用于疫苗中以在较长时间内保持较高的抗体滴度。 这个项目的基本原理和创新来自于它帮助确定最佳使用这些 在最脆弱的老年人群体之一-那些长期接受护理的人-中接种两种疫苗 (LTC)如疗养院（Nursing Home）。总体而言，他们提出的免疫原性和临床分析 这里有必要提供支持和理由，以确定是否需要一个更加昂贵多站点 临床终点RCT比较这两种疫苗是必要的。 假设：佐剂流感疫苗Fluad在免疫学上不劣于HD流感疫苗， 接受长期护理的老年人。他们建议进行一项非劣效性随机临床试验， 65岁及以上的NH居民以1：1的比例接种Fluad或HD疫苗。血液样本将在 以及接种疫苗后（接种疫苗后1个月）和流感季节结束后进行盲法实验室分析。 目标1.主要目的：确定Fluad在免疫学上是否非劣效于HD流感病毒 65岁以上的居民接种疫苗。 目的2：次要目的：确定Fluad的异源免疫力是否高于HD 疫苗 目的3：初步临床目的：确定Fluad是否具有与HD疫苗相似的保护效力。