A pilot randomised blinded placebo-controlled trial of paracetamol for later treatment of a patent ductus arteriosus.

OBJECTIVE: To explore the efficacy and risks of oral paracetamol in later (>2 weeks old) treatment of patent ductus arteriosus (PDA). STUDY DESIGN: A multicentre double-blind placebo-controlled randomised pilot trial in three neonatal intensive care units in Australia. Infants born <33 weeks with haemodynamically significant PDA were treated with a 5-day course of oral paracetamol or placebo. Cardiac ultrasounds were used to document haemodynamic parameters. The primary outcome analysed was ductal closure by 48 h after treatment completion. Secondary outcomes included reduction in ductal diameter >25% and safety. RESULTS: Fifty-five infants were enrolled, of whom 27 received paracetamol and 28 placebo. Eighty percent had received previous non-steroidal anti-inflammatory drug. Mean postnatal age was 25 days. Four of the 27 ducts treated with paracetamol closed vs. 0/28 treated with placebo (p = 0.05). An additional 13/27 given  paracetamol vs. 7/28 given placebo showed significant constriction (p = 0.008). No adverse effects were observed . CONCLUSIONS: There was some evidence of increased closure with oral paracetamol at postnatal age >2 weeks; however, the overall efficacy was not high.

Correction: A pilot randomised blinded placebo-controlled trial of paracetamol for later treatment of a patent ductus arteriosus.

In the published version of this paper the author Yan Chen was missed out of the author list. This has now been corrected in the HTML and PDF versions of the paper.

A randomised placebo-controlled trial of early treatment of the patent ductus arteriosus.

OBJECTIVE: Failure of closure of the patent ductus arteriosus (PDA) may be associated with harm. Early cardiac ultrasound-targeted treatment of a large PDA may result in a reduction in adverse outcomes and need for later PDA closure with no increase in adverse effects. STUDY DESIGN: Multicentre, double-blind, placebo-controlled randomised trial. SETTING: Three neonatal intensive care units in Australia. PATIENTS AND INTERVENTIONS: Eligible infants born <29 weeks were screened for a large PDA and received indomethacin or placebo before age 12 h. MAIN OUTCOME: Death or abnormal cranial ultrasound. RESULTS: The trial ceased enrolment early due to lack of availability of indomethacin. 164 eligible infants were screened before 12 h; of the 92 infants with a large PDA, 44 were randomised to indomethacin and 48 to placebo. There was no difference in the main outcome between groups. Infants receiving early indomethacin had significantly less early pulmonary haemorrhage (PH) (2% vs 21%), a trend towards less periventricular/intraventricular haemorrhage (PIVH) (4.5% vs 12.5%) and were less likely to receive later open-label treatment for a PDA (20% vs 40%). The 72 non-randomised infants with a small PDA were at low risk of pulmonary haemorrhage and had an 80% spontaneous PDA closure rate. CONCLUSIONS: Early cardiac ultrasound-targeted treatment of a large PDA is feasible and safe, resulted in a reduction in early pulmonary haemorrhage and later medical treatment but had no effect on the primary outcome of death or abnormal cranial ultrasound. REGISTERED TRIAL: Australian New Zealand Clinical Trials Registry (ACTRN12608000295347).