TRANSFORM-HF DCC

变换-HF DCC

• 批准号: 9310535
• 负责人: Kevin J Anstrom
• 金额: $ 84.25万
• 依托单位: DUKE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-08-15 至 2022-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9310535
• 关键词: Acute; Address; American; American Heart Association; Ancillary Study; Applications Grants; Belief; Biomedical Research; Cardiology; Cardiovascular system; Caring; Clinical; Clinical Research; Clinical Trials; Clinical Trials Data Monitoring Committees; Clinical effectiveness; Collaborations; Companions; Complement; Congestive; Data; Data Collection; Data Coordinating Center; Data Element; Data Quality; Development; Diuretics; Doctor of Philosophy; Economic Burden; Enrollment; Environment; Equipoise; Formulation; Fostering; Furosemide; Future; Generic Drugs; Guidelines; Heart failure; Hospitalization; Hospitals; Leadership; Liquid substance; Mission; Monitor; Monitoring Clinical Trials; Morbidity - disease rate; National Heart, Lung, and Blood Institute; Oral; Organization and Administration; Outcome; Patients; Pharmacodynamics; Phase; Phase III Clinical Trials; Population; Pragmatic clinical trial; Procedures; Productivity; Protocols documentation; Randomized; Recruitment Activity; Research; Research Institute; Research Personnel; Risk; Site; Statistical Data Interpretation; Symptoms; Testing; Time; Treatment Failure; United States; Validation; Vital Status; Woman; aged; arm; base; clinical practice; college; comparative effectiveness; cost; data acquisition; data integration; data management; design; dissemination research; ethnic minority population; experience; flexibility; follow-up; health related quality of life; improved; improved outcome; innovation; medication compliance; mortality; operation; payment; programs; prospective; prototype; racial minority; tool; treatment duration; treatment effect; treatment strategy

Heart Failure (HF) is the most frequent cause of hospitalization among patients aged 65 or greater and leads to an enormous personal, societal and economic burden for the US population. Loop diuretics such as torsemide and furosemide are a cornerstone of HF therapy utilized to improve congestive symptoms. Prior data suggest that torsemide compared to furosemide advantageously alters pathophysiological mechanisms associated with progression, has a favorable pharmacodynamic profile and may decrease HF morbidity and mortality. Yet, furosemide is overwhelmingly utilized in daily practice which highlights clinical equipoise and an unmet need for an adequately powered study to definitively determine whether torsemide compared to furosemide improves outcomes to guide clinical practice. The ToRsemide compArisoN with furoSemide FOR Management of HF (TRANSFORM-HF) trial is a robustly-powered, prospective, randomized, comparative-effectiveness study which will change guidelines and have immediate clinical implications for the management of millions of patients with HF. The primary hypothesis of the TRANSFORM-HF trial is that torsemide will reduce all-cause mortality by a relative 15% compared with furosemide over a period of 12 months. Important secondary hypotheses include that torsemide compared to furosemide will 1) reduce 1-year all-cause mortality and first HF re-hospitalization; 2) improve health-related quality of life; and 3) increase survival time and decrease total cardiovascular hospitalizations compared with furosemide. The specific aims of the TRANSFORM-HF Clinical Coordinating Center (CCC) and Data Coordinating Center (DCC) are to (1) Develop and administrate a clinical trial organization to efficiently coordinate study conduct and analysis; (2) Implement and monitor a “real-world”, large-scale, pragmatic, clinical-effectiveness study using streamlined data acquisition with call center follow-up, and (3) Disseminate the trial results and implications to a broad audience and serve as a prototype for future pragmatic clinical trials. Our prospective, unblinded, 2-arm, phase III clinical trial of 6,000 hospitalized HF patients targeting robust enrollment of racial and ethnic minorities and women will randomize subjects 1:1 to either oral torsemide or furosemide prior to discharge. Enrollment will occur at 50 US hospital sites with established HF clinical excellence. A systematic data acquisition approach will minimize investigator and subject burden and use a call center at 6 and 12 months to document vital status, medication adherence, and health-related quality of life, and to acquire hospitalization information. The TRANSFORM-HF trial will be led by investigators and an operations team with substantial experience and expertise in HF care, clinical trials, data integration and administration working within the highly proven environment of the Duke Clinical Research Institute. This application is submitted as two clustered R01 grant proposals which detail a CCC (PI-Dr. Velazquez) and a DCC (PIs-Drs. Anstrom and Eisenstein). This proposal presents the DCC application.

心力衰竭（HF）是65岁或以上患者住院的最常见原因， 给美国人民带来巨大的个人、社会和经济负担。髓袢利尿剂，如 托拉塞米和呋塞米是用于改善充血症状的HF治疗的基础。之前 数据表明，与呋塞米相比，托拉塞米有利地改变了病理生理机制， 与疾病进展相关，具有良好的药效学特征，可降低HF发病率， mortality.然而，呋塞米在日常实践中被压倒性地使用，这突出了临床平衡和 一项充分把握度研究的未满足需求，以明确确定托拉塞米与 呋塞米改善预后以指导临床实践。托拉塞米与呋塞米的比较 FOR HF管理（TRANSFORM-HF）试验是一项具有强大把握度的前瞻性随机试验， 比较有效性研究，这将改变指导方针，并立即临床 这对数百万HF患者的管理具有重要意义。的主要假设 TRANSFORM-HF试验表明，与对照组相比， 在12个月的时间里服用呋塞米。重要的次要假设包括，与 呋塞米将1）降低1年全因死亡率和首次HF再住院率; 2）改善健康相关 生活质量;和3）与对照组相比， 呋塞米。TRANSFORM-HF临床协调中心（CCC）的具体目标和数据 协调中心（DCC）的职责是（1）建立和管理临床试验组织， 协调研究的进行和分析;（2）实施和监测一个“现实世界”，大规模，务实， 临床有效性研究，使用简化的数据采集和呼叫中心随访，以及（3）传播 试验结果和影响，以广泛的受众，并作为一个原型，为未来的务实临床 审判我们在6，000例住院HF患者中进行的前瞻性、非盲、2组、III期临床试验， 少数民族和女性的稳健入组将受试者1：1随机分配至口服 Torsemide或速尿出院前。入组将在50家已确诊HF的美国医院研究中心进行 临床卓越系统的数据采集方法将最大限度地减少研究者和受试者的负担， 在6个月和12个月时使用呼叫中心记录生命状态、药物依从性和健康相关质量 并获取住院信息。TRANSFORM-HF试验将由研究者和一名 运营团队在HF护理、临床试验、数据集成和 在杜克临床研究所的高度成熟的环境中工作。这 申请是作为两个集群R 01赠款建议提交的，其中详细说明了CCC（PI博士。Velazquez）和 DCC（PIs-Anstrom和Eisenstein博士）。本提案提出了DCC应用。