Treatment allocation scheme.

BackgroundHemodynamic insufficiency occurs when tissue oxygen delivery fails to meet demand. Preterm infants are vulnerable to early circulatory failure after birth, impacting mortality and morbidity. Mean arterial pressure is not a reliable indicator of systemic blood flow. Low superior vena cava (SVC) flow, independent of fetal shunts, has been proposed as a robust biomarker of circulatory impairment in this population. Dobutamine, a selective β1 agonist with minimal effect on systemic vascular resistances, is considered the treatment of choice for this condition. However, information about its optimal dosing, efficacy, safety, and pharmacokinetic/pharmacodynamic (PK/PD) profile in preterm infants is limited.MethodsA multicenter, low-intervention, dose-finding trial will be conducted to establish the minimum effective dose of dobutamine to treat hemodynamic insufficiency, defined as SVC flow 55 mL/kg/min). The proportion of patients achieving and maintaining adequate hemodynamic status with dobutamine alone during the first 72 hours (efficacy), side effects, and variables explaining interindividual PK/PD variability will be explored.DiscussionThis study aims to define the minimum dose of dobutamine with a relevant PD effect on circulation in infants with hemodynamic insufficiency during transitional circulation. This is the first step towards future randomized clinical trials on efficacy and safety of dobutamine for the proposed indication.Trial registrationEU Clinical trials register, EU CT 2023-504915-34-00, registered 18 April 2023.