Banovic Marko, Loncar Zlatibor, Behfar Atta, Vanderheyden Marc, Beleslin Branko, Zeiher Andreas, Metra Marco, Terzic Andre, Bartunek Jozef
Cardiology Department, University Clinical Center of Serbia, Belgrade Medical School, 11000, Belgrade, Serbia.
Mayo Clinic, Rochester, MN, 55905, USA.
Stem Cell Res Ther. 2015 Aug 29;6(1):159. doi: 10.1186/s13287-015-0143-9.
Despite multimodal regimens and diverse treatment options alleviating disease symptoms, morbidity and mortality associated with advanced ischemic heart failure remain high. Recently, technological innovation has led to the development of regenerative therapeutic interventions aimed at halting or reversing the vicious cycle of heart failure progression. Driven by the unmet patient need and fueled by encouraging experimental studies, stem cell-based clinical trials have been launched over the past decade. Collectively, these trials have enrolled several thousand patients and demonstrated the clinical feasibility and safety of cell-based interventions. However, the totality of evidence supporting their efficacy in ischemic heart failure remains limited. Experience from the early randomized stem cell clinical trials underscores the key points in trial design ranging from adequate hypothesis formulation to selection of the optimal patient population, cell type and delivery route. Importantly, to translate the unprecedented promise of regenerative biotherapies into clinical benefit, it is crucial to ensure the appropriate choice of endpoints along the regulatory path. Accordingly, we here provide considerations relevant to the choice of endpoints for regenerative clinical trials in the ischemic heart failure setting.
尽管多模式治疗方案和多样的治疗选择可缓解疾病症状，但晚期缺血性心力衰竭相关的发病率和死亡率仍然很高。最近，技术创新推动了旨在阻止或逆转心力衰竭进展恶性循环的再生治疗干预措施的发展。在未满足的患者需求驱动下，并受到鼓舞人心的实验研究推动，过去十年间开展了基于干细胞的临床试验。总体而言，这些试验已招募了数千名患者，并证明了基于细胞干预的临床可行性和安全性。然而，支持其在缺血性心力衰竭中疗效的全部证据仍然有限。早期随机干细胞临床试验的经验强调了从充分的假设制定到最佳患者群体、细胞类型和给药途径选择等试验设计中的关键点。重要的是，要将再生生物疗法前所未有的前景转化为临床益处，在监管过程中确保适当选择终点至关重要。因此，我们在此提供与缺血性心力衰竭背景下再生临床试验终点选择相关的考量因素。
