A randomised placebo-controlled trial of early treatment of the patent ductus arteriosus
- 1Department of Neonatology, Royal North Shore Hospital, Sydney, Australia
- 2University of Sydney, Australia
- 3Centre for Neonatal Research and Education, University of Western Australia, Perth, Western Australia, Australia
- 4Royal Prince Alfred Women and Babies Hospital, Sydney, Australia
- Correspondence to Dr Martin Kluckow, Department of Neonatology, Royal North Shore Hospital, Level 5, Douglas Building, St Leonards, Sydney, NSW 2065, Australia;
- Received 20 June 2013
- Revised 6 November 2013
- Accepted 10 November 2013
- Published Online First 6 December 2013
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).