Intravenous paracetamol in comparison with ibuprofen for the treatment of patent ductus arteriosus in preterm infants: a randomized controlled trial

Carlo Dani, Gianluca Lista, Silvia Bianchi, Fabio Mosca, Federico Schena, Luca Ramenghi, Enrico Zecca, Giovanni Vento, Chiara Poggi, Valentina Leonardi, Diego Minghetti, Maria Teresa Rosignoli, Fabrizio Calisti, Alessandro Comandini, Agnese Cattaneo, Paola Lipone, Carlo Dani, Gianluca Lista, Silvia Bianchi, Fabio Mosca, Federico Schena, Luca Ramenghi, Enrico Zecca, Giovanni Vento, Chiara Poggi, Valentina Leonardi, Diego Minghetti, Maria Teresa Rosignoli, Fabrizio Calisti, Alessandro Comandini, Agnese Cattaneo, Paola Lipone

Abstract

Our aim was to assess the efficacy and safety of intravenous (i.v.) paracetamol vs. i.v. ibuprofen for the treatment of hemodynamically significant patent ductus arteriosus (hsPDA) in preterm infants. This is a multicenter randomized controlled study. Infants with a gestational age of 25+0-31+6 weeks were randomized to receive i.v. paracetamol (15 mg/kg/6 h for 3 days) or i.v. ibuprofen (10-5-5 mg/kg/day). The primary outcome was the closure rate of hsPDA after the first treatment course with paracetamol or ibuprofen. Secondary outcomes included the constriction rate of hsPDA, the re-opening rate, and the need for surgical closure. Fifty-two and 49 infants received paracetamol or ibuprofen, respectively. Paracetamol was less effective in closing hsPDA than ibuprofen (52 vs. 78%; P = 0.026), but the constriction rate of the ductus was similar (81 vs. 90%; P = 0.202), as confirmed by logistic regression analysis. The re-opening rate, the need for surgical closure, and the occurrence of adverse effects were also similar.Conclusions: Intravenous paracetamol was less effective in closing hsPDA than ibuprofen, but due to a similar constriction effect, its use was associated with the same hsPDA outcome. These results can support the use of i.v. paracetamol as a first-choice drug for the treatment of hsPDA.Trial registration: Clinicaltrials.gov : NCT02422966, Date of registration: 04/09/2015; EudraCT no: 2013-003883-30. What is Known: • The successful closure of patent ductus arteriosus with oral paracetamol has been recently reported in several preterm infants, but only one randomized controlled study investigated the efficacy of intravenous paracetamol. What is New: • Intravenous paracetamol is less effective in closing hsPDA than ibuprofen, but have a similar constriction effect. • These results can support the use of i.v. paracetamol as a first-choice drug for the treatment of hsPDA.

Keywords: Paracetamol; Patent ductus arteriosus; Preterm infant.

Conflict of interest statement

CD received fees for consultancy from Angelini S.p.A. GL, SB, FM, FS, LR, EZ, GV, CP, VL, and DM declare no conflicts of interest. MTR, FC, AC, AC, and PL are fully employees in Angelini S.p.A.

Figures

Fig. 1
Fig. 1
Patient disposition and statistical study populations: m-ITT population, PP population, and SP
Fig. 2
Fig. 2
Logistic regression analysis: Closed DA vs. not hsPDA + hsPDA
Fig. 3
Fig. 3
Logistic regression analysis: Closed DA + not hsPDA vs. hsPDA

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