Kobayashi Kumi, Kobayashi Kei, Liu Christopher, Ryan Julia, Zurakowski David, Ishibashi Nobuyuki
Center for Neuroscience Research and Sheikh Zayed Institute for Pediatric Surgical Innovation, Children's National Hospital, Washington, DC, USA.
Children's National Heart Center, Children's National Hospital, Washington, DC, 20010, USA.
Pediatr Cardiol. 2025 Jun;46(5):1296-1311. doi: 10.1007/s00246-024-03550-5. Epub 2024 Jun 25.
Phase 1 trials are primarily conducted to evaluate the safety and feasibility of new interventions, usually without recruiting control patients. This retrospective study aims to characterize clinical and biological outcomes in historical and contemporary cases of neonates and infants undergoing two-ventricle repair to facilitate future secondary endpoint analyses for such trials. This retrospective study included neonates/infants (ages ≤ 6 months) who underwent two-ventricle repair between 2015 and 2021 using the same criteria as our phase 1 trial (n = 199). Patients were allocated into the ventricular septal defect (n = 61), the Tetralogy of Fallot (TOF, n = 88), and the transposition of the great arteries (n = 50) groups with an additional comparison between two eras (2015-2019 vs. 2020-2021). Patient characteristics and most variables assessed were different between the three diagnostic groups indicating the importance of diagnostic matching for secondary analyses. Although the era did not alter cerebral/somatic oxygenation, ventricular function, neuroimaging findings, and complication rates, we observed improvement of inotropic and/or vasoactive-inotropic scores in all groups during the more recent era. In 2020-2021, the age and the body weight at the operation were higher, and hospital stay was shorter in the TOF group, suggesting the possible impact of the pandemic. Results also indicated that matching altered characteristics such as age at operation that may limit the temporal effects and optimize secondary analyses. Using optimal contemporary cases and historical data based on this study will assist in developing a comprehensive study design for a future efficacy/effectiveness trial.
1期试验主要用于评估新干预措施的安全性和可行性，通常不招募对照患者。这项回顾性研究旨在描述接受双心室修复的新生儿和婴儿在历史和当代病例中的临床和生物学结局，以便为这类试验的未来次要终点分析提供便利。这项回顾性研究纳入了2015年至2021年间接受双心室修复的新生儿/婴儿（年龄≤6个月），采用与我们的1期试验相同的标准（n = 199）。患者被分为室间隔缺损组（n = 61）、法洛四联症（TOF，n = 88）组和大动脉转位组（n = 50），并对两个时期（2015 - 2019年与2020 - 2021年）进行了额外比较。三个诊断组之间的患者特征和评估的大多数变量不同，这表明诊断匹配对于次要分析的重要性。尽管时期并未改变脑/体氧合、心室功能、神经影像学结果和并发症发生率，但我们观察到在最近一个时期所有组的强心和/或血管活性 - 强心评分均有所改善。在2020 - 2021年，TOF组的手术年龄和体重更高，住院时间更短，这表明大流行可能产生了影响。结果还表明，匹配改变了手术年龄等特征，这可能会限制时间效应并优化次要分析。基于本研究使用最佳的当代病例和历史数据将有助于为未来的疗效/有效性试验制定全面的研究设计。
