title: Efficacy and safety of intravenous paracetamol in comparison to ibuprofen for the treatment of patent ductus arteriosus in preterm infants: study protocol for a randomized control trial.
abstract: BACKGROUND
  Patent ductus arteriosus (PDA) is one of most common complications in preterm infants. Although ibuprofen represents the first choice for the closure of PDA, this treatment can cause severe gastrointestinal and adverse renal effects and worsen platelet function. The successful closure of the PDA with paracetamol has been recently reported in several preterm infants, and the safety of paracetamol for this use has been suggested by the available data.
  
  
  METHODS
  We present the design of a randomized, multicenter, controlled study, whose aim is to assess the effectiveness and safety of intravenous paracetamol in comparison to intravenous ibuprofen for the treatment of PDA in preterm infants. A total of 110 infants born at 25(+0) to 31(+6) weeks of gestational age will be enrolled and randomized to receive paracetamol or ibuprofen (55 patients per group) starting at 24-72 h of life. The primary endpoint of the study is the comparison of the PDA closing rate observed after a 3-day course with paracetamol or ibuprofen. The secondary endpoints include the closure rate of PDA after the second course of treatment with ibuprofen, the re-opening rate of the PDA, the incidence of surgical ligation, and the occurrence of adverse effects.
  
  
  CONCLUSIONS
  The results of this study will provide new information about the possible use of paracetamol in the treatment of PDA. Paracetamol could offer several important therapeutic advantages over current treatment options, and it could become the treatment of choice for the management of PDA, mainly due to its more favorable side effect profile.
  
  
  BACKGROUND
  Clinicaltrials.gov NCT02422966 . Eudract no. 2013-003883-30.
authors.affiliation: Department of Neuroscience, Psychology, Drug Research and Child Health, Careggi University Hospital of Florence, Largo Brambilla 3, 50134, Firenze, Italy. cdani@unifi.it.
authors.forename: Carlo
authors.initials: C
authors.lastname: Dani
authors.affiliation: Division of Neonatology, Careggi University Hospital of Florence, Largo Brambilla 3, 50134, Firenze, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Poggi
authors.affiliation: Neonatal Intensive Care Unit, Department of Mother and Infant Science, Fondazione IRCCS "Ca' Granda" Ospedale Maggiore Policlinico, University of Milan, Via Della Commenda 12, 20122, Milano, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Mosca
authors.affiliation: Neonatal Intensive Care Unit, Department of Mother and Infant Science, Fondazione IRCCS "Ca' Granda" Ospedale Maggiore Policlinico, University of Milan, Via Della Commenda 12, 20122, Milano, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Schena
authors.affiliation: Division of Neonatology, "V. Buzzi" Children Hospital of Milan, Via Castelvetro 22, 20154, Milan, Italy.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Lista
authors.affiliation: Department of Neonatology Obstetrics and Neuroscience, G. Gaslini Children's University Hospital of Genova, Via Gerolamo Gaslini 5, 16147, Genova, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Ramenghi
authors.affiliation: Division of Neonatology, Catholic University of Rome, Largo Agostino Gemelli 8, 00168, Roma, Italy.
authors.forename: Costantino
authors.initials: C
authors.lastname: Romagnoli
authors.affiliation: Angelini S.p.A. - Piazzale della Stazione, 00071, S. Palomba -Pomezia, Roma, Italy.
authors.forename: Enrica
authors.initials: E
authors.lastname: Salvatori
authors.affiliation: Angelini S.p.A. - Piazzale della Stazione, 00071, S. Palomba -Pomezia, Roma, Italy.
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Rosignoli
authors.affiliation: Angelini S.p.A. - Piazzale della Stazione, 00071, S. Palomba -Pomezia, Roma, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Lipone
authors.affiliation: Angelini S.p.A. - Piazzale della Stazione, 00071, S. Palomba -Pomezia, Roma, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Comandini
mesh_terms: D000082:Acetaminophen / Q000008:administration & dosage* / Q000009:adverse effects; D018712:Analgesics, Non-Narcotic / Q000008:administration & dosage* / Q000009:adverse effects; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D002985:Clinical Protocols; D004374:Ductus Arteriosus, Patent / Q000000981:diagnostic imaging / Q000188:drug therapy*; D005865:Gestational Age; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage* / Q000009:adverse effects; D062071:Infant, Extremely Premature; D007231:Infant, Newborn; D007234:Infant, Premature; D007262:Infusions, Intravenous; D007558:Italy; D011446:Prospective Studies; D012107:Research Design; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018712:Analgesics, Non-Narcotic; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000082:Acetaminophen; D007052:Ibuprofen
keywords: Paracetamol; Patent ductus arteriosus; Preterm infant