TRANSFORM-HF DCC

变换-HF DCC

• 批准号: 9768524
• 负责人: Kevin J Anstrom
• 金额: $ 72.87万
• 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/9768524
• 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; 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; 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; hospital readmission; improved; improved outcome; innovation; medication compliance; mortality; operation; payment; programs; prospective; prototype; racial minority; recruit; 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。循环利尿剂，如 速尿和速尿是用来改善充血症状的HF疗法的基石。之前 数据表明，与速尿相比，妥塞米有利地改变了病理生理机制 与进展相关，具有良好的药效学特征，并可降低心衰发病率和 死亡率。然而，速尿在日常实践中被压倒性地使用，这突显了临床均衡性和 尚未满足的需求是进行一项足够有力的研究，以明确确定托塞米特与 速尿可改善疗效以指导临床实践。速尿与速尿的比较 对于HF的管理(Transform-HF)试验是一项强大的、前瞻性的、随机的、 将改变指南并立即进行临床应用的比较有效性研究 对数百万心力衰竭患者管理的启示。该理论的基本假设 Transform-HF试验表明，与其他药物相比，妥塞米特可将全因死亡率降低15% 速尿的疗程为12个月。重要的次要假设包括托塞米特与 速尿将1)减少1年全因死亡率和首次心衰再住院；2)改善与健康相关的 生活质量；以及3)增加生存时间和减少心血管住院总次数 速尿。TRANSAGE-HF临床协调中心(CCC)的具体目标和数据 协调中心(DCC)的任务是(1)发展和管理临床试验组织，以有效地 协调研究进行和分析；(2)实施和监测一个“真实世界”、大规模、务实、 使用简化的数据采集和呼叫中心跟踪的临床效果研究，以及(3)传播 试验结果和对广大受众的影响，并作为未来实用临床的原型 审判。我们对6,000名住院心衰患者进行的前瞻性、非盲法、双臂、III期临床试验 种族和少数民族和妇女的强劲登记将使受试者1：1随机化 出院前服用速尿或速尿。将在50个已建立心衰的美国医院进行登记 临床表现卓越。系统的数据采集方法将最大限度地减少调查员和受试者的负担，并 在6个月和12个月时使用呼叫中心记录生命状态、服药依从性和与健康相关的质量 以及获取住院信息。Transform-HF试验将由调查人员和一名 运营团队在心力衰竭护理、临床试验、数据集成和 在杜克临床研究所高度成熟的环境中工作的行政管理人员。这 申请是以两个聚类的R01拨款提案提交的，其中详细说明了CCC(PI-DR)。Velazquez)和 DCC(PI-Dr.Anstrom和Eisenstein)。这份提案介绍了DCC的应用。