TY - JOUR
T1 - Study design and rationale for ELPIS
T2 - A phase I/IIb randomized pilot study of allogeneic human mesenchymal stem cell injection in patients with hypoplastic left heart syndrome
AU - Kaushal, Sunjay
AU - Wehman, Brody
AU - Pietris, Nicholas
AU - Naughton, Casey
AU - Bentzen, Soren M.
AU - Bigham, Grace
AU - Mishra, Rachana
AU - Sharma, Sudhish
AU - Vricella, Luca
AU - Everett, Allen D.
AU - Deatrick, Kristopher B.
AU - Huang, Sihong
AU - Mehta, Helina
AU - Ravekes, William A.
AU - Hibino, Naru
AU - Difede, Darcy L.
AU - Khan, Aisha
AU - Hare, Joshua M.
N1 - Funding Information:
This study has been funded by the Maryland Stem Cell Research Fund and Children's Heart Foundation, and by internal funds from the University of Maryland and Interdisciplinary Stem Cell Institute at the Miller School of Medicine, University of Miami. This trial is listed at www.clinicaltrials.gov. Dr Hare discloses a relationship with Vestion Inc and Longeveron LLC that includes equity, board membership, and consulting. Vestion Inc and Longeveron LLC did not participate in funding this work. None of the other authors declare a conflict of interest. All authors have approved the final version of the trial.
Publisher Copyright:
© 2017 Elsevier Inc.
PY - 2017/10
Y1 - 2017/10
N2 - Despite advances in surgical technique and postoperative care, long-term survival of children born with hypoplastic left heart syndrome (HLHS) remains limited, with cardiac transplantation as the only alternative for patients with failing single ventricle circulations. Maintenance of systemic right ventricular function is crucial for long-term survival, and interventions that improve ventricular function and avoid or defer transplantation in patients with HLHS are urgently needed. We hypothesize that the young myocardium of the HLHS patient is responsive to the biological cues delivered by bone marrow–derived mesenchymal stem cells (MSCs) to improve and preserve right ventricle function. The ELPIS trial (Allogeneic Human MEsenchymal Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome: An Open Label Pilot Study) is a phase I/IIb trial designed to test whether MSC injection will be both safe and feasible by monitoring the first 10 HLHS patients for new major adverse cardiac events. If our toxicity stopping rule is not activated, we will proceed to the phase IIb component of our study where we will test our efficacy hypothesis that MSC injection improves cardiac function compared with surgery alone. Twenty patients will be enrolled in a randomized phase II trial with a uniform allocation to MSC injection versus standard surgical care (no injection). The 2 trial arms will be compared with respect to improvement of right ventricular function, tricuspid valve annulus size, and regurgitation determined by cardiac magnetic resonance and reduced mortality, morbidity, and need for transplantation. This study will establish the safety and feasibility of allogeneic mesenchymal stem cell injection in HLHS patients and provide important insights in the emerging field of stem cell–based therapy for congenital heart disease patients.
AB - Despite advances in surgical technique and postoperative care, long-term survival of children born with hypoplastic left heart syndrome (HLHS) remains limited, with cardiac transplantation as the only alternative for patients with failing single ventricle circulations. Maintenance of systemic right ventricular function is crucial for long-term survival, and interventions that improve ventricular function and avoid or defer transplantation in patients with HLHS are urgently needed. We hypothesize that the young myocardium of the HLHS patient is responsive to the biological cues delivered by bone marrow–derived mesenchymal stem cells (MSCs) to improve and preserve right ventricle function. The ELPIS trial (Allogeneic Human MEsenchymal Stem Cell Injection in Patients with Hypoplastic Left Heart Syndrome: An Open Label Pilot Study) is a phase I/IIb trial designed to test whether MSC injection will be both safe and feasible by monitoring the first 10 HLHS patients for new major adverse cardiac events. If our toxicity stopping rule is not activated, we will proceed to the phase IIb component of our study where we will test our efficacy hypothesis that MSC injection improves cardiac function compared with surgery alone. Twenty patients will be enrolled in a randomized phase II trial with a uniform allocation to MSC injection versus standard surgical care (no injection). The 2 trial arms will be compared with respect to improvement of right ventricular function, tricuspid valve annulus size, and regurgitation determined by cardiac magnetic resonance and reduced mortality, morbidity, and need for transplantation. This study will establish the safety and feasibility of allogeneic mesenchymal stem cell injection in HLHS patients and provide important insights in the emerging field of stem cell–based therapy for congenital heart disease patients.
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U2 - 10.1016/j.ahj.2017.06.009
DO - 10.1016/j.ahj.2017.06.009
M3 - Article
C2 - 28938963
AN - SCOPUS:85027421135
SN - 0002-8703
VL - 192
SP - 48
EP - 56
JO - American heart journal
JF - American heart journal
ER -