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).