Protein Therapeutics to Prevent Heart Failure Post Myocardial Infarction

预防心肌梗塞后心力衰竭的蛋白质疗法

• 批准号: 7867072
• 负责人: John C Burnett
• 金额: $ 75.03万
• 依托单位: MAYO CLINIC ROCHESTER
• 依托单位国家: 美国
• 财政年份: 2010
• 资助国家: 美国
• 起止时间: 2010-04-01 至 2012-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7867072
• 关键词: Acute myocardial infarction; Address; American Heart Association; Biology; Brain natriuretic peptide; Cardiac; Cardiac Myocytes; Cells; Chronic; Clinical; Clinical Research; Clinical Trials Data Monitoring Committees; Data; Functional disorder; Future; Health; Healthcare; Heart Injuries; Heart failure; Human; Incidence; Instruction; Kidney; Morbidity - disease rate; Myocardial; Myocardial Infarction; Natriuretic Peptides; Outcome; Peptides; Prevalence; Prevention; Property; Reporting; Research; Research Personnel; Safety; Sample Size; Scientist; Site; Specialized Center; Structure; Syndrome; Therapeutic; Translational Research; Translations; base; cost; efficacy trial; follow-up; human study; meetings; mortality; novel; novel therapeutic intervention; peptide B; prevent; programs; repaired; therapeutic protein

DESCRIPTION (provided by applicant): The broad objective of this application is to establish that the endogenous cardiac peptide B-type natriuretic peptide (BNP) is a novel and efficacious protein therapeutic for human acute myocardial infarction (AMI) to preserve myocardial structure and function reducing ultimately the burden of human heart failure (HP). This highly translational research builds upon ongoing basic and clinical research pursued by the applicants and currently supported by HL83231 (Cardiac Peptides in Myocardial Infarction). Our application specifically takes advantage of the cardioprotective properties of this small and endogenous myocardial peptide in protecting the heart from injury and promoting cardiac repair. Our therapeutic strategy is based upon the emerging biology of BNP, which goes beyond renal actions and includes direct actions on cardiomyocytes and non-myocyte cardiac cells. The Specific Aims are as follows: Aim 1: To collect clinical outcome data beyond the 30 days follow up in the pilot human study supported by HL83231 so as to use this data to calculate sample size and power calculation for the multicenter "Prevention of Post Myocardial Infarction Heart Failure Safety and Efficacy Trial" to be supported by the P50 program. Aim 2: Organize the Scientific Advisory Board and Steering Committee consisting of both scientists and clinical experts to draft the plan for the multicenter "Prevention of Post Myocardial Infarction Heart Failure Safety and Efficacy Trial." We will also organize the Data and Safety Monitoring Board (DSMB). Aim 3: Engage a clinical research organization (CRO) to begin plans for site recruitment and regulatory management of the proposed multicenter "Prevention of Post Myocardial Infarction Heart Failure Safety and Efficacy Trial" that will be supported by the F50 program. Aim 4: To engage the FDA in amending our investigator held IND for the use of BNP in human myocardial infarction to include our multicenter "Prevention of Post Myocardial Infarction Heart Failure Safety and Efficacy Trial" to be supported by the P50 program. We believe that our proposal meets the objectives of the C-TRIF P20 Program and accelerates translation of promising new therapeutic interventions such as BNP for AMI to reduce the burden of future HF. RELEVANCE (See instructions): Chronic heart failure (CHF) is a clinical syndrome with significant mortality and morbidity despite recent advances in the understanding of the pathophysiology and treatment. The latest figures from the American Heart Association reports a prevalence of 5 million with incidence of 550,000 cases, annual mortality of 52,000 and a total cost of 28 billion dollars in healthcare expense per year in the US. This research will aid in addressing this health challenge.

描述（由申请人提供）： 本申请的主要目标是确定内源性心脏肽 B 型利尿钠肽 (BNP) 是一种新型有效的蛋白质治疗剂，用于治疗人类急性心肌梗塞 (AMI)，以保护心肌结构和功能，最终减轻人类心力衰竭 (HP) 的负担。这项高度转化性的研究建立在申请人正在进行的基础和临床研究的基础上，目前得到 HL83231（心肌梗塞中的心肌肽）的支持。我们的应用特别利用了这种小内源性心肌肽的心脏保护特性，以保护心脏免受损伤并促进心脏修复。我们的治疗策略基于 BNP 的新兴生物学，它超越了肾脏作用，还包括对心肌细胞和非肌细胞心肌细胞的直接作用。具体目标如下： 目标1：收集HL83231支持的试点人体研究超过30天随访的临床结果数据，以便利用这些数据计算P50计划支持的多中心“预防心肌梗死后心力衰竭安全性和有效性试验”的样本量和功效计算。目标2：组织由科学家和临床专家组成的科学顾问委员会和指导委员会，起草多中心“预防心肌梗死后心力衰竭安全性和有效性试验”计划。我们还将组织数据和安全监控委员会（DSMB）。目标 3：聘请临床研究组织 (CRO) 开始计划对拟议的多中心“预防心肌梗死后心力衰竭安全性和有效性试验”进行现场招募和监管管理，该试验将由 F50 计划支持。目标 4：让 FDA 参与修改我们的研究者持有的 BNP 在人类心肌梗塞中使用的 IND，将我们的多中心“预防心肌梗塞后心力衰竭安全性和有效性试验”纳入 P50 计划的支持。我们相信，我们的提案符合 C-TRIF P20 计划的目标，并加速了有前景的新治疗干预措施的转化，例如用于 AMI 的 BNP，以减轻未来心力衰竭的负担。 相关性（参见说明）：慢性心力衰竭（CHF）是一种具有显着死亡率和发病率的临床综合征，尽管最近对病理生理学和治疗的理解取得了进展。美国心脏协会的最新数据报告称，美国每年的患病人数为 500 万，发病人数为 55 万例，年死亡率为 52,000 人，医疗费用总额为 280 亿美元。这项研究将有助于解决这一健康挑战。