639 - SCEMPI Trial in Preterm Infants with Intraventricular Hemorrhage: Early Phase Experience and Trial Implementation.

Publication Number: 2624.639

Anushka Acharya, Johns Hopkins University School of Medicine, Yorktown, VA, United States; Kathryn Lowe, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Lauren E. Guyer, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Hawley Helmbrecht, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Lauren Jantzie, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Xiaobu Ye, Johns Hopkins University School of Medicine, Baltimore, MD, United States; Shenandoah Robinson, Johns Hopkins University, Baltimore, MD, United States

Background: The Safety of Combination of Erythropoietin and Melatonin for Preterm Infants with Intraventricular Hemorrhage (SCEMPI NCT05617833) is a clinical research study to investigate the safety of high-dose melatonin plus erythropoietin (EPO) in babies born before 32 weeks postmenstrual age (PMA) with intraventricular hemorrhage (IVH). The study is currently being conducted in the NICUs at Johns Hopkins (JH) in Baltimore, with a planned expansion to JH All Children’s Hospital NICU in Florida.

Objective: SCEMPI was developed by a multidisciplinary team and underwent extensive regulatory review. During early implementation, unanticipated barriers to enrollment were identified related to the physical, logistical, social and emotional challenges families face when dealing with an unexpected preterm birth. Issues and solutions were systematically evaluated to identify important lessons applicable to future neonatal clinical trials.

Design/Methods: SCEMPI is multi-site, single institution, two-step clinical trial to evaluate the safety of high-dose enteral melatonin and EPO given from enrollment up to 34 weeks PMA, followed by a 4-week inpatient monitoring period. The open label Step 1 enrollment has been accrued. Analysis of Step 1 serum, biomarker, and stool microbiome samples is underway. The primary endpoint is death and serious adverse events related to either study drug.

Results: Following an operational lead-in phase, 6 neonates have been enrolled in the open-label Step 1 phase, with treatment thus far showing good tolerability. Trial enrollment is currently paused, pending Data Safety Monitoring Board review. The blinded, randomized, placebo-controlled Step 2 is planned to begin in early 2026. Unanticipated issues impacting accrual primarily arose from the medical, emotional and socioeconomic burdens of very preterm delivery, coupled with regional hospital economics and enrollment windows.

Conclusion(s): The aim of high dose melatonin and EPO cocktail treatment is to replenish hormonal deficits due to preterm birth, promote neurodevelopment and potentially reduce subsequent lifelong shunt dependence. Early experience from SCEMPI suggests favorable safety and supports the long duration interventional clinical trials in the NICU. Importantly, strong teamwork and diligent communication between the entire clinical and research teams has proven essential throughout all phases of the trial, especially during family and patient enrollment and timely sample collection. Ongoing evaluation continues to help refine the best practices for implementing clinical trials in this fragile patient population.