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

Authors

Kei Kobayashi, Center for Neuroscience Research and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, DC, USA.
Tessa Higgins, Center for Neuroscience Research and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, DC, USA.
Christopher Liu, Center for Neuroscience Research and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, DC, USA.
Mobolanle Ayodeji, Center for Neuroscience Research and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, DC, USA.
Gil Wernovsky, Children's National Heart Institute, Children's National Hospital, Washington, DC, USA.
Richard A. Jonas, Center for Neuroscience Research and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, DC, USA.
Nobuyuki Ishibashi, Center for Neuroscience Research and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, DC, USA.

Document Type

Journal Article

Publication Date

8-22-2022

Journal

Cardiology in the young

DOI

10.1017/S1047951122002633

Keywords

CHD; clinical trial; patient outcome assessment

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.

APA Citation

Kobayashi, Kei; Higgins, Tessa; Liu, Christopher; Ayodeji, Mobolanle; Wernovsky, Gil; Jonas, Richard A.; and Ishibashi, Nobuyuki, "Defining the optimal historical control group for a phase 1 trial of mesenchymal stromal cell delivery through cardiopulmonary bypass in neonates and infants" (2022). GW Authored Works. Paper 1450.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/1450

Department

Pediatrics