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，并导致 给美国民众带来巨大的个人、社会和经济负担。 托拉塞米和呋塞米是用于改善充血症状的心力衰竭治疗的基石。 数据表明，与呋塞米相比，托拉塞米有利地改变病理生理机制 与进展相关，具有良好的药效学特征，并可能降低心力衰竭发病率 然而，呋塞米在日常实践中被广泛使用，这凸显了临床平衡和死亡率。 尚未满足需要进行充分有力的研究来明确确定托拉塞米是否与 呋塞米可改善结果以指导临床实践。 FOR 心衰管理 (TRANSFORM-HF) 试验是一项强有力的、前瞻性的、随机的、 比较有效性研究将改变指南并立即产生临床效果 对数百万心力衰竭患者治疗的影响。 TRANSFORM-HF 试验表明，与相比，托拉塞米可将全因死亡率降低相对 15% 重要的次要假设包括托拉塞米与 12 个月期间的对比。 速尿将 1) 降低 1 年全因死亡率和首次心力衰竭再住院率 2) 改善健康相关状况； 生活质量；3) 与相比，延长生存时间并减少心血管住院总人数 TRANSFORM-HF 临床协调中心 (CCC) 的具体目标和数据 协调中心 (DCC) 将 (1) 建立和管理临床试验组织，以有效地 协调研究的进行和分析；（2）实施和监测“现实世界”的、大规模的、务实的、 使用简化的数据采集和呼叫中心跟进进行临床有效性研究，以及 (3) 传播 试验结果及其对广大受众的影响，并作为未来实用临床的原型 我们针对 6,000 名住院心力衰竭患者进行的前瞻性、非盲法、2 组 III 期临床试验。 种族和族裔少数群体以及女性的大量入学将以 1:1 的比例将受试者随机分配到口服 托拉塞米或呋塞米将在出院前在 50 个已确诊心力衰竭的美国医院进行登记。 卓越的临床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况、用药依从性和健康相关质量 TRANSFORM-HF 试验将由研究人员和一名医生领导。 运营团队在心力衰竭护理、临床试验、数据集成和 管理工作在杜克临床研究所经过高度验证的环境中进行。 申请以两份集群 R01 拨款提案形式提交，其中详细说明了 CCC（PI-Dr. Velazquez）和 DCC（PI-Anstrom 和 Eisenstein 博士）。该提案介绍了 DCC 应用。