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情况。因此，DFG开始了“Nachwuchsakademie Klinische Studien”计划。最近，申请者成功地完成了该计划内的DFG拨款，现在他的科学工作集中在心脏患者的临床试验上。现代药物为心脏病患者提供了新的抗血栓药物，但在减少血栓栓塞症并发症的同时又不增加这些患者的出血风险仍然是一个挑战。该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。第二个目标是改善心脏病患者的抗血栓治疗和临床结果。该项目将在斯坦福大学(美国)的斯坦福临床研究中心进行，由临床研究领域的专家哈林顿教授和马哈菲教授指导。为了保证全方位的方法学培训，申请者将参与临床试验的所有阶段：概念阶段、进行中阶段和最后阶段。重点在于随机对照试验(RCT)的设计和实现。这项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)患者的临床结果，HPR的定义是高比率的ADP-TRAP诱导的血小板聚集。患者将被随机分成两组，要么继续接受抗血小板治疗，要么改用第三代P2Y12拮抗剂。作为第二个项目，申请者计划设计和进行一项对经皮冠状动脉介入治疗后房颤患者进行的RCT的血小板功能亚研究。申请者的目标是识别HPR患者，并比较不同的抗血栓策略。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，申请者将改善他的经验并形成国际合作。申请者将参与制定时间表和里程碑，以完成正在进行的临床试验，并对已完成的大型结果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，申请者将学习临床研究中心的结构，并为未来的合作开发全球调查网络。获得的知识和调查网络将使申请者能够在德国建立一个临床研究中心。第一个项目的结果将证明，在选定的患者中改用抗血小板治疗是否可以改善冠状动脉介入治疗后的临床结果。在第二个项目中，将确定用于经皮冠状动脉介入治疗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.