Establishing Optimal Control Cohorts for Phase 1 Trials: Retrospective Analysis of Clinical and Biological Outcomes in Neonates and Infants Undergoing Two-Ventricle Repair

Kumi Kobayashi ^1,2, Kei Kobayashi ^1,2, Christopher Liu ³

¹Center for Neuroscience Research and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, DC, USA.
²Children's National Heart Center, Children's National Hospital, Washington, DC, 20010, USA.
³Virginia Commonwealth University School of Medicine, Richmond, VA, USA.
⁴The George Washington University School of Medicine and Health Sciences, Washington, DC, USA.
⁵Departments of Anesthesiology and Surgery, Harvard Medical School, Boston Children's Hospital, Boston, MA, USA.
⁶Center for Neuroscience Research and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, DC, USA. nishibas@childrensnational.org.
⁷Children's National Heart Center, Children's National Hospital, Washington, DC, 20010, USA. nishibas@childrensnational.org.
⁸The George Washington University School of Medicine and Health Sciences, Washington, DC, USA. nishibas@childrensnational.org.
⁹Children's National Hospital, 111 Michigan Avenue, NW, Washington, DC, USA. nishibas@childrensnational.org.

⁰Center for Neuroscience Research and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, DC, USA.

Pediatric Cardiology +

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June 25, 2024

View abstract on PubMed

Summary

This study analyzed outcomes in infants undergoing two-ventricle repair, finding improved inotropic scores in a recent era. This data aids future clinical trial design for pediatric heart conditions.

Area Of Science

Pediatric Cardiology
Clinical Trial Design
Congenital Heart Disease

Background

Phase 1 trials assess new intervention safety and feasibility, often without controls.
Two-ventricle repair is a critical procedure for neonates and infants with congenital heart defects.
Characterizing outcomes is essential for designing future efficacy trials.

Purpose Of The Study

To characterize clinical and biological outcomes in neonates and infants undergoing two-ventricle repair.
To provide data for secondary endpoint analyses in future clinical trials.
To compare outcomes between historical and contemporary patient cohorts.

Main Methods

Retrospective analysis of 199 neonates/infants (≤6 months) undergoing two-ventricle repair (2015-2021).
Patients grouped by diagnosis: Ventricular Septal Defect (VSD), Tetralogy of Fallot (TOF), Transposition of the Great Arteries (TGA).
Comparison between two eras (2015-2019 vs. 2020-2021) and impact of diagnostic matching analyzed.

Main Results

Patient characteristics differed significantly across diagnostic groups (VSD, TOF, TGA).
No significant era-based differences in oxygenation, ventricular function, neuroimaging, or complication rates.
Improvement in inotropic/vasoactive-inotropic scores observed in the recent era (2020-2021).
TOF group in 2020-2021 showed higher age/weight at operation and shorter hospital stay, potentially pandemic-related.
Diagnostic matching influenced characteristics like age at operation, impacting temporal effect analysis.

Conclusions

Diagnostic matching is crucial for secondary analyses in two-ventricle repair trials.
While core physiological outcomes were stable, inotropic support improved in the recent era.
This study provides valuable data for designing future pediatric cardiac surgery efficacy trials.

Keywords:

CHD Clinical trial Patient outcome assessment Postoperative score