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Defining the optimal historical control group for a phase 1 trial of mesenchymal stromal cell delivery through cardiopulmonary bypass in neonates and infants

Published online by Cambridge University Press:  22 August 2022

Kei Kobayashi Open the ORCID record for Kei Kobayashi [Opens in a new window] ,
Tessa Higgins ,
Christopher Liu ,
Mobolanle Ayodeji ,
Gil Wernovsky ,
Richard A. Jonas  and
Nobuyuki Ishibashi
Kei Kobayashi
Affiliation:
Center for Neuroscience Research and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National Hospital, Washington, DC, USA Children’s National Heart Institute, Children’s National Hospital, Washington, DC, USA
Tessa Higgins
Affiliation:
Center for Neuroscience Research and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National Hospital, Washington, DC, USA The George Washington University School of Medicine and Health Sciences, Washington, DC, USA
Christopher Liu
Affiliation:
Center for Neuroscience Research and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National Hospital, Washington, DC, USA Virginia Commonwealth University School of Medicine, Richmond, VA, USA
Mobolanle Ayodeji
Affiliation:
Center for Neuroscience Research and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National Hospital, Washington, DC, USA
Gil Wernovsky
Affiliation:
Children’s National Heart Institute, Children’s National Hospital, Washington, DC, USA The George Washington University School of Medicine and Health Sciences, Washington, DC, USA
Richard A. Jonas
Affiliation:
Center for Neuroscience Research and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National Hospital, Washington, DC, USA Children’s National Heart Institute, Children’s National Hospital, Washington, DC, USA The George Washington University School of Medicine and Health Sciences, Washington, DC, USA
Nobuyuki Ishibashi*
Affiliation:
Center for Neuroscience Research and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children’s National Hospital, Washington, DC, USA Children’s National Heart Institute, Children’s National Hospital, Washington, DC, USA The George Washington University School of Medicine and Health Sciences, Washington, DC, USA
*
Author for correspondence: Nobuyuki Ishibashi, MD, Children’s National Hospital, 111 Michigan Avenue, NW, Washington, DC, 20010, USA. Tel: +1 202 476 2388. E-mail: nishibas@childrensnational.org
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Abstract

Objective:

The Mesenchymal Stromal Cell Delivery through Cardiopulmonary Bypass in Pediatric Cardiac Surgery study is a prospective, open-label, single-centre, dose-escalation phase 1 trial assessing the safety/feasibility of delivering mesenchymal stromal cells to neonates/infants during cardiac surgery. Outcomes will be compared with historical data from a similar population. We aim to define an optimal control group for use in the Mesenchymal Stromal Cell Delivery through Cardiopulmonary Bypass in Pediatric Cardiac Surgery trial.

Methods:

Consecutive patients who underwent a two-ventricle repair without aortic arch reconstruction within the first 6 months of life between 2015 and 2020 were studied using the same inclusion/exclusion criteria as the Phase 1 Mesenchymal Stromal Cell Delivery through Cardiopulmonary Bypass in Pediatric Cardiac Surgery trial (n = 169). Patients were allocated into one of three diagnostic groups: ventricular septal defect type, Tetralogy of Fallot type, and transposition of the great arteries type. To determine era effect, patients were analysed in two groups: Group A (2015–2017) and B (2018–2020). In addition to biological markers, three post-operative scoring methods (inotropic and vasoactive-inotropic scores and the Pediatric Risk of Mortality-III) were assessed.

Results:

All values for three scoring systems were consistent with complexity of cardiac anomalies. Max inotropic and vasoactive-inotropic scores demonstrated significant differences between all diagnosis groups, confirming high sensitivity. Despite no differences in surgical factors between era groups, we observed lower inotropic and vasoactive-inotropic scores in group B, consistent with improved post-operative course in recent years at our centre.

Conclusions:

Our studies confirm max inotropic and vasoactive-inotropic scores as important quantitative measures after neonatal/infant cardiac surgery. Clinical outcomes should be compared within diagnostic groupings. The optimal control group should include only patients from a recent era. This initial study will help to determine the sample size of future efficacy/effectiveness studies.

Keywords

CHDpatient outcome assessmentclinical trial
Type
Original Article
Information
Cardiology in the Young , Volume 33 , Issue 9 , September 2023 , pp. 1523 - 1528
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Copyright
© The Author(s), 2022. Published by Cambridge University Press

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