Paediatric trials for dobutamine safety

Neonatal circulatory failure in the first two days after birth impairs blood flow, resulting in brain injury and decreased neurodevelopment. A European consortium is addressing the efficacy and safety of the drug dobutamine in treating infants.

Health

Dobutamine is used to treat infants with abnormally low blood pressure (hypotension) after birth. Preliminary data indicates that dobutamine treatment is beneficial. However, the current formulation is not certified for safe use in infants and it is being used off-label. The EU-funded NEO-CIRC (Dobutamine for neonatal circulatory failure defined by novel biomarkers) project will conduct clinical trials to determine the safety and efficacy of age-appropriate formulation of dobutamine for infants. Other areas of focus include potential genetic polymorphisms that may influence drug response in infants and determining a standardised definition for circulatory failure in infants. Project members revised their paediatric investigation plan and obtained approval for a series of three clinical trials. These studies will test dobutamine efficacy in preterm neonates using a new age-appropriate neonatal drug formulation. During the second project phase, significant progress was achieved towards launching the clinical trials. NEO-CIRC finalised experimental studies on animal models to determine dobutamine pharmacokinetics (PK) and pharmacodynamics (PD). Analysis of PK/PD in tissue and blood samples is ongoing. Requisite manuals and standard operating protocols were also finalised. Project findings were published in several peer-reviewed journals, and communicated in nine oral conference presentations and one poster presentation. Moreover, one publication is currently under review and another two are being prepared. Staff training as well as preparatory work for clinical trial, sample and data management, regulatory framework and pilot batch of trial medicines has been completed. The pilot batch of medicines has already been distributed to two clinical study sites. Overall, the NEO-CIRC trials will provide important information on the kinetics, dynamics and safety of administering dobutamine in infants as treatment for hypotension. Importantly, the adapted drug formulation for infants, alongside the improved consensus definition of neonatal circulatory failure, will improve the clinical outcome of affected babies.