title: Endpoints in stem cell trials in ischemic heart failure.
abstract: 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.
authors: Cardiology Department, University Clinical Center of Serbia, Belgrade Medical School, 11000, Belgrade, Serbia. markobanovic71@gmail.com.
authors: Marko
authors: M
authors: Banovic
authors: Cardiology Department, University Clinical Center of Serbia, Belgrade Medical School, 11000, Belgrade, Serbia. zl.loncar@gmail.com.
authors: Zlatibor
authors: Z
authors: Loncar
authors: Mayo Clinic, Rochester, MN, 55905, USA. Behfar.Atta@mayo.edu.
authors: Atta
authors: A
authors: Behfar
authors: Cardiovascular Center, OLV Hospital, 9300, Aalst, Belgium. marc.vanderheyden@olvz-aalst.be.
authors: Marc
authors: M
authors: Vanderheyden
authors: Cardiology Department, University Clinical Center of Serbia, Belgrade Medical School, 11000, Belgrade, Serbia. branko.beleslin@gmail.com.
authors: Branko
authors: B
authors: Beleslin
authors: Cardiology Department, Goethe University of Frankfurt, 60590, Frankfurt, Germany. zeiher@em.uni-frankfurt.de.
authors: Andreas
authors: A
authors: Zeiher
authors: Cardiology Department, University of Brescia, 25123, Brescia, Italy. metramarco@libero.it.
authors: Marco
authors: M
authors: Metra
authors: Mayo Clinic, Rochester, MN, 55905, USA. terzic.andre@mayo.edu.
authors: Andre
authors: A
authors: Terzic
authors: Cardiovascular Center, OLV Hospital, 9300, Aalst, Belgium. jozef.bartunek@olvz-aalst.be.
authors: Jozef
authors: J
authors: Bartunek
mesh_terms: D023381:Endpoint Determination; D006333:Heart Failure / Q000628:therapy*; D006801:Humans; D017202:Myocardial Ischemia / Q000628:therapy*; D016032:Randomized Controlled Trials as Topic / Q000379:methods* / Q000592:standards / Q000706:statistics & numerical data; D033581:Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods