Dobutamine for NEOnatal CIRCulatory failure defined by novel biomarkers

Dobutamine and adrenaline are widely used as second line therapy for systemic hypotension in infants. Dopamine is currently the most widely used first line drug. In neonates, sustained hypotension may, and impaired organ perfusion will, cause brain injury and poor neurodevelopmental outcomes. All three catecholamines are currently used off-label and have different modes of action which may result in potentially harmful haemodynamic effects. No reliable safety or efficacy data exists for the use of these drugs in neonates or newborns. Furthermore, no uniform criteria exist to define hypotension and there is little evidence to support current intervention strategies, which vary widely. Recently, superior vena cava (SVC) flow has been proposed as a more reliable indicator of circulatory failure than low blood pressure and preliminary results suggest Dobutamine is the optimum therapeutic in such cases.

NEO-CIRC proposes:
1) a randomised placebo controlled trial to provide safety and efficacy data for Dobutamine as a first line inotrope for all gestational ages
2) to perform pre-clinical; pharmacokinetic; pharmacodynamic; metabolomic and pharmacogenomic studies
3) to develop improved biomarkers of hypotension
4) to develop and adapt a formulation of Dobutamine suitable for newborns with the aim to apply for a Paediatric Use Marketing Authorisation.

The NEO-CIRC consortium includes international experts in neonatal medicine, pharmacology, pharmacogenomics, drug formulation and pre-clinical neonatal models and an experienced group of experienced multicentre clinical trials NICUs. Outcomes anticipated include improved biomarkers of organ perfusion; a new consensus definition of neonatal circulatory failure and answers to key clinical practice uncertainties, including variability of response to Dobutamine in common pathophysiologies seen in newborn infants impact on longer term developmental outcomes so important to the patients, families and wider society.