Harvard Regional Clinical Center of the NHLBI Heart Failure Network

描述(由申请人提供)：目前NHLBI心力衰竭(HF)网络的哈佛地区临床中心(RCC)，包括一个临床研究技能开发核心，期待扩展为一个三角形，其中3个独特协调和支持的HF项目将加速NHBLI改善心力衰竭患者未来的使命。通过利用实时数据库和现场人群的多样性，研究患者在该RCC内的招募将得到加强。计划创建新的网络资产，使用公共数据字段，将单个网络试验连接起来，以成倍增加Netwrk的科学产量。这些资产将为心力衰竭护理领域当前的挑战提供信息，例如防止住院，识别扩张型心肌病的新病理突变，以及确定左心室射血分数改善的患者的特征。哈佛RCC将为研究的设计和实施提供协作领导，这些研究解决了如果没有NHLBI的赞助就无法回答的关键机制和治疗问题。一个例子是一项三臂比较有效性研究，以确定铁补充对心力衰竭患者运动能力和心功能的影响(IRONOUT HF)。本研究将加深对心力衰竭生理学影响的认识，并探索治疗心力衰竭缺铁的方法。主要终点是静脉补铁、口服补铁或安慰剂24周后峰值耗氧量的变化。如果显示出益处，与更昂贵和更不方便的静脉铁治疗相比，口服铁将被评估为非劣势。这项研究还将评估低水平运动时骨骼肌氧的利用，并将血红蛋白、铁储存、铁调节蛋白海普西丁和新的铁依赖代谢谱的变化与运动能力的变化联系起来，以确定最有可能从铁补充中受益的患者。临床研究技能开发核心支持严格的课程设置、实验室实践经验和导师评审委员会，以培训和激励新的HF临床研究人员。利用网络资产，计划建立一个学徒调查员网络，整个HF网络的研究员将合作成为下一代临床调查人员。 相关性(见说明)：心力衰竭是美国健康日益沉重的负担，只有通过NHLBI心力衰竭网络等倡议的领先调查人员的合作才能减轻这种负担。哈佛地区临床中心建议加入该领域的其他领先者的行列，进行IRONOUT HF等研究，测试口服或静脉补铁治疗心力衰竭患者缺铁是否会提高运动能力。

DESCRIPTION (provided by applicant): The Harvard Regional Clinical Center (RCC) of the current NHLBI Heart Failure (HF) Network, including a Clinical Research Skills Development Core, looks forward to expanding into a triangle where 3 uniquely aligned and supported HF programs will accelerate the mission of the NHBLI to improve the future for HF patients. Study patient recruitment within this RCC will be enhanced through utilization of real-time databases and diversity of site populations. Creation of new Network Assets is planned, using common data fields that will bridge individual Network trials to multiply the scientific yield of the Netwrk. These Assets will inform current challenges in HF care, such as preventing hospitalizations, identifying new pathologic mutations in dilated cardiomyopathy, and characterizing patients with improved LVEF. The Harvard RCC will provide collaborative leadership for design and implementation of studies that address vital mechanistic and therapeutic questions that cannot be answered without NHLBI sponsorship. One example is a 3-arm comparative effectiveness study to determine Iron Repletion Effects on Exercise Capacity and Cardiac Function in Heart Failure (IRONOUT HF). This study will add to the understanding of the physiologic impact and explore treatments of iron deficiency in HF. The primary endpoint will be change in peak oxygen consumption after 24 weeks of intravenous iron, oral iron, or placebo. If benefit is shown, oral iron will be assessed for non-inferiority compared to the more expensive and inconvenient therapy with intravenous iron. This study will also assess skeletal muscle oxygen utilization during low level exercise, and relate changes in hemoglobin, iron stores, the iron-regulatory protein hepcidin, and novel iron-dependent metabolomic profiles to changes in exercise capacity in order to identify patients most likely to benefit from iron repletion. The Clinical Research Skills Development Core supports a rigorous course curriculum, hands-on-laboratory experience, and a Mentor Review Board to train and inspire new HF clinical investigators. Utilizing the Network Assets, an Apprentice Investigator Network is planned where fellows throughout the HF Network will collaborate to become the next generation of clinical investigators. RELEVANCE (See instructions): Heart failure is a growing burden on US health that can only be diminished by the collaboration of leading investigators through initiatives such as the NHLBI Heart Failure Network. The Harvard Regional Clinical Center proposes to join other leaders in the field in studies such as IRONOUT HF, testing whether treatment of iron deficiency in heart failure patients with either oral or intravenous iron will improve exercise capacity.