Table 1.

Trial synopsis

Study title	Early PARacetamol to promote early closure of the ductus arteriosus
Study aims	To study the effect of early treatment of patent ductus arteriosus with paracetamol To examine the safety and efficacy profile of paracetamol during the early postnatal period
Outcomes	Primary: any intervention for management of PDA up to 5 days Secondary: closure of ductus arteriosus at 5 days; size of ductus arteriosus at 48 hours and 5 days; ductal reopening during admission; ductus arteriosus parameters; systemic blood flow measurements; adverse events during the treatment period; mortality; significant morbidities
Design	Double-blind, placebo-controlled, parallel, two-arm, randomised, phase II single-centre trial, stratified by gestational age and size of ductus at initial assessment
Inclusion criteria	Babies <6 hours old Born <29 weeks’ gestation Ductus arteriosus ≥1.0 mm; <30% R-L shunt Informed parental consent
Exclusion criteria	Known congenital anomalies Haemodynamic instability (>1 ionotropic agent) Abnormal baseline liver function Clinician decision to give indomethacin prophylaxis Ductus arteriosus <1.0 mm; ≥30% R-L shunt
Intervention	Intervention: intravenous paracetamol 15 mg/kg loading; 7.5 mg/kg maintenance Control: intravenous 5% dextrose 1.5 mL/kg loading; 0.75 mL/kg maintenance
Study product	Active: paracetamol 10 mg/mL Placebo: 5% dextrose
Treatment schedule	Loading dose to be given at 6 hours after clinician performed ultrasound; maintenance doses to be given every 6 hours for total 5 days Routine assessments to be performed at 48 hours and 5 days The treating team will manage infants enrolled in the study as they would manage any other infant. If there is a clinical decision that a PDA requires intervention, based on either a routine assessment or otherwise, the trial intervention will be discontinued. Intervention and ongoing management will then be at the discretion of the treating neonatologist
Preparation	Both paracetamol and 5% dextrose are clear, colourless and indistinguishable. 1.5 mL/kg (loading) or 0.75 mL/kg (maintenance) of active treatment or placebo will be prepared and administered as per hospital protocol for paracetamol
Blood samples	Liver function tests to be added routine blood tests; paracetamol levels to be added to blood tests on day 2 and day 5; all blood tests should be add-ons, no additional blood samples are required
Sample size	n=100; 50/group; assuming that approximately 60% of infants in this study would otherwise have required intervention for PDA, a sample size of at least 42 infants per group would be required to detect a 50% reduction in the need for intervention, with 95% CI and power of 80%

PDA, patent ductus arteriosus.