The design and conduct of clinical trials for antithrombotic regimes in cardiac patients

德国需要了解临床试验的设计和实施。因此，DFG开始了“Nachwuchsakademie Klinische Escheren”计划。最近，申请人成功地完成了该计划中的DFG拨款，现在他的科学工作主要集中在心脏病患者的临床试验上。现代药物为心脏病患者提供了新的抗血栓形成方案，并且在这些患者中找到减少血栓栓塞并发症而不产生过度出血风险的最佳平衡仍然是一个挑战。本项目的第一个目标是获得临床试验设计和实施方面的知识，并将这些知识引入德国。第二个目的是改善心脏病患者的抗血栓治疗和临床结局。该项目将在斯坦福大学（美国）的斯坦福大学临床研究中心进行，由临床研究领域的专家哈灵顿教授和马哈菲教授指导。为了保证全方位的方法学培训，申请人将参与临床试验的所有阶段：概念，正在进行的和最后阶段。主要焦点在于随机对照试验（RCT）的设计和实现。本试验旨在改善经皮冠状动脉介入治疗（PCI）后高血小板反应性（HPR）患者的临床结局，高血小板反应性（HPR）定义为ADP-TRAP诱导的血小板聚集率高。患者将被随机分配继续接受抗血小板治疗或改用第三代P2 Y12拮抗剂。作为第二个项目，申请人计划在PCI后房颤患者中设计并实施RCT的血小板功能子研究。申请方旨在识别HPR患者并比较不同的抗血栓形成策略。通过与正在进行的大型临床结果研究的教师领导和运营团队合作，申请人将提高他的经验并形成国际合作。申请人将参与创建时间表和里程碑，以完成正在进行的临床试验，并对已完成的大型结局试验的数据进行二次分析，以了解临床试验结果并将结果整合到临床实践中。其次，申请人将学习临床研究中心的结构，并为未来的合作开发全球研究网络。获得的知识和研究网络将使申请人能够在德国建立临床研究中心。第一个项目的结果将证明在选定的患者中转换抗血小板治疗是否可以改善PCI后的临床结局。在第二个项目中，将确定PCI术后房颤患者的最佳抗血栓治疗方案。进一步的二次分析将有助于解决抗血栓治疗的重要临床心脏问题。

Germany suffers a need for knowledge of the design and conduct in clinical trials. Therefore, the DFG began the program ´Nachwuchsakademie Klinische Studien´. Recently, the applicant successfully completed a grant of the DFG within this program and now focuses his scientific work on clinical trials in cardiac patients. Modern drugs offer new antithrombotic regimes for cardiac patients and it is still a challenge to find the optimal balance of reducing thromboembolic complications without running an excessive bleeding risk in those patients. The first objective of this project is to acquire knowledge of the design and conduct in clinical trials and import this knowledge to Germany. The second objective is to improve antithrombotic therapy and clinical outcome in cardiac patients. The project will take place at the Stanford Center for Clinical Research of Stanford University (USA) under the mentoring of Prof. Harrington and Prof. Mahaffey, experts in the field of clinical investigation. In order to guarantee a full spectrum of methodological training the applicant will be involved in all stages of clinical trials: the conceptual, the ongoing and the final stage. The main focus lies in the design and realization of a randomized controlled trial (RCT). This trial aims to improve clinical outcome of patients after percutaneous coronary intervention (PCI) with high platelet reactivity (HPR) defined by a high ratio of ADP-TRAP induced platelet aggregation. Patients will be randomized to either stay with their antiplatelet therapy or switch to third generation P2Y12 antagonists. As a second project the applicant plans to design and conduct a platelet function substudy of a RCT in patients with atrial fibrillation after PCI. The applicant aims to identify patients with HPR and compare different antithrombotic strategies. By working with the faculty leadership and operational teams running an ongoing large clinical outcome study, the applicant will improve his experience and form international collaborations. The applicant will be involved with the creation of timelines and milestones to complete an ongoing clinical trial and perform secondary analyzes of data from a completed large outcome trial to understand the clinical trial results and integration of findings in clinical practice. Secondarily, the applicant will learn the structures of a clinical research center and develop global investigative networks for future collaboration. The acquired knowledge and the investigative network will enable the applicant to establish a clinical research center in Germany. The results of the first project will demonstrate if switching antiplatelet therapy in selected patients can improve clinical outcome after PCI. In a second project the best antithrombotic regime for patients with atrial fibrillation after PCI will be identified. Further secondary analyzes will help to resolve important clinical cardiac issues of antithrombotic therapy.