245 - Randomised Placebo-Controlled Trial of Early Targeted Treatment of Patent Ductus Arteriosus with Paracetamol in Extremely Low Birth Weight Infants – Pilot Study (ETAPA – Phase 1)

Poster Number: 245
Publication Number: 245.127

Niamh Ó Catháin, Coombe Women and Infants University Hospital/University College Dublin, Dublin, Ireland, Dublin, Dublin, Ireland; Jana Semberova, The Coombe hospital, Dublin 8, Dublin, Ireland; Eugene Dempsey, university college cork, Cork, Cork, Ireland; Zbynek Stranak, Charles University, Prague, Hlavni mesto Praha, Czech Republic; Jan Janota, Charles Univerdity Prague, Praha 6, Hlavni mesto Praha, Czech Republic; Robert B. McGrath, Coombe Women & Infants University Hospital, Dublin, Dublin, Ireland; John Kelleher, Coombe Women & Infants University Hospital, Dublin, Dublin, Ireland; Anne Doolan, The Coombe Hospital/University College Dublin, Dublin 8, Dublin, Ireland; Anne O Sullivan, The Children's Regional Hospital at Coopern, Dublin, Dublin, Ireland; Peter J. Duddy, The Coombe Hospital, Dublin & University College Cork, Dublin 8, Dublin, Ireland; Orla Franklin, CHI@Crumlin, Rathmines Dublin, Dublin, Ireland; Mandy Daly, Irish Neonatal Health Alliance, BRAY, Wicklow, Ireland; Aisling Martin, The Coombe Hospital, Dublin, Dublin, Ireland; Jan Miletin, Coombe Women and Infants University Hospital, Dublin, Dublin, Ireland

Background:
The efficacy and basic safety of Paracetamol in the treatment of Patent Ductus Arteriosus (PDA) is established and Paracetamol has been shown to be as effective as Indomethacin and Ibuprofen for PDA closure, with reduced associated adverse effects.


Objective:
To determine whether early targeted treatment of PDA with Paracetamol in Extremely Low Birth Weight (ELBW) infants results in significant reduction of adverse outcomes attributable to hypoperfusion (peri/intraventricular haemorrhage (PIVH), necrotising enterocolitis (NEC) and death). The aim of this pilot study (Phase 1) was to refine the Protocol and enrolment before proceeding to the multi-centre, international randomised trial (Phase 2).


Design/Methods:
Parallel group, randomised, double-blinded, placebo-controlled trial. Phase 1 is an internal pilot study involving 30 ELBW babies to enable refinement of the trial processes and procedures before extension of the trial to all study centres (Phase 2 - 218 participants total). ELBW infants with PDA diameter more than 1.5mm and non-restrictive left to right PDA flow between 6 and 12 hours of age were eligible for enrolment. Participants were randomised to Paracetamol or placebo (1:1) administered intravenously 6-hourly, until ductal closure as determined by serial 48-hourly echocardiography assessment, to a maximum of six completed days. Based on our inclusion/exclusion criteria we expected to enrol approximately 60% of the ELBW infants admitted to the participating centres. We planned to start Phase 2 if more than 75% of participants would be treated as per Protocol.


Results: Fifty ELBW infants were admitted to the participating centres during Phase 1, 40 were consented and screened (80%), with 29 infants randomised (58%) (see Figure 1). Median gestation was 26.0 weeks (IQR 2.1) and median birth weight was 790g (IQR 245). No participants were unblinded, and none received open-label treatment during the trial intervention period. All participants were treated as per Protocol. Of the non-randomised infants five infants had PDA < 1.5mm and/or restrictive flow. PDA was closed spontaneously before discharge in all of these infants. The other six non-randomised infants had PPHN/bidirectional shunt, with high mortality (66.7%) and morbidity (combined outcome of PIVH/NEC/Death of 83.3%) in this group.

 

Conclusion(s):
We confirmed our estimated enrolment to the trial and the trial protocol has been adhered to. The results to date indicate that the trial selection criteria is appropriate for targeting infants that might benefit most from early targeted treatment of PDA.