Single centre, dose finding trial to establish the minimum effective dose of dobutamine required to treat hemodynamic insufficiency, defined as low superior vena cava (SVC) flow, in infants below 33 weeks' gestation during transitional circulation (first 72 hours from birth).
Born with up to 32(+6) weeks gestation
Presence of hemodynamic insufficiency, defined as SVC flow <51 ml/kg/min.
Provision of signed and dated informed consent form by father/mother or legally designated representative, which can be given antenatally.
Neonates considered non-viable, with a clinical decision not to provide life support
Infants with severe congenital hydrops fetalis needing chest or peritoneal drainage before recruitment
Infants already on dobutamine treatment
Infants with congenital malformations likely to affect cardiovascular adaptation (including: congenital diaphragmatic hernia, gastroschisis or congenital heart defects)
Parallel
Intravenous dobutamine 5 mcg/kg/min
DrugIntravenous dobutamine will be administered at a dose of 5 mcg/kg/min.
Intravenous dobutamine 7.5 mcg/kg/min
DrugIntravenous dobutamine will be administered at a dose of 7.5 mcg/kg/min.
Intravenous dobutamine 10 mcg/kg/min
DrugIntravenous dobutamine will be administered at a dose of 10 mcg/kg/min.
Intravenous dobutamine 12.5 mcg/kg/min
DrugIntravenous dobutamine will be administered at a dose of 12.5 mcg/kg/min.
Intravenous dobutamine 15 mcg/kg/min
DrugIntravenous dobutamine will be administered at a dose of 15 mcg/kg/min.
Minimum dobutamine dose to reach and maintain a SVC flow above 55 ml/kg/min
Short-term pharmacodynamics (PD) endpoint: Minimum dobutamine dose to reach and maintain a superior vena cava (SVC) flow above 55 ml/kg/min on an echocardiogram performed at 1 and 3 hours after effective infusion of the allocated dose. The effective start of the infusion (t0) will be calculated as the time at which the infusion pump is switched on plus the empirical value for the interval arising from the dead space. We summarize t0 as "the time at which dobutamine is expected to reach the circulation"
Proportion of neonates achieving and maintaining a clinically acceptable haemodynamic status
Proportion of neonates achieving and maintaining a clinically acceptable haemodynamic status with the dobutamine infusion alone in the first 72 hours from birth. Acceptable hemodynamic status is defined as the achievement and maintenance of dose success during the first 72 h from birth. The loss of such acceptable haemodynamic status occurs whenever there is a change in therapeutic strategy that involves cardiovascular treatment other than dobutamine alone due to exceeded safety parameters, treatment failure of the investigational infusion or the need for rescue treatment or death; any additional fluid bolus is considered as cardiovascular treatment.
Absolute and relative frequencies of adverse events and severe adverse events
Absolute and relative frequencies of adverse events (AEs) and severe adverse events (SAEs), to be recorded and compared between groups. AEs are defined as any untoward medical occurrence in a patient or clinical investigation patients administered a medicinal product, which does not necessarily have a causal relationship with this treatment (the study medication). SAEs are defined as any untoward medical occurrence that at any dose: * Results in death, * Is life-threatening * Requires inpatient hospitalization or prolongation of existing hospitalization * Results in persistent or significant disability/incapacity, or * Is a congenital anomaly/birth defect. * Other important medical events.
Click on the lead sponsor to view all of their trials.
