Paracetamol vs Ibuprofen for PDA Closure in Preterm Infants.
Paracetamol vs Ibuprofen for PDA Closure in Preterm Infants.
Current pharmacological options to treat an hemodynamically significant PDA (HsPDA) in
 preterm infants are limited to non-selective cyclo-oxygenase (COX) inhibitors, indomethacin
 or ibuprofen. Recently paracetamol exposure has been reported to successful closure of PDA.
 Aim of this randomized double-blind controlled study is to compare the efficacy and the
 safety of standard PDA treatment ibuprofen versus paracetamol-experimental treatment . We
 hypothesize that paracetamol is more effective than ibuprofen in closing PDA, perhaps
 ameliorating the safety profile of the pharmacological treatment.
The objective of this trial is to compare the efficacy and safety of 2 therapeutic regimens
 for PDA treatment in a population of preterm newborns of gestational age (GA) <31+6 weeks
 with respiratory distress syndrome (RDS) and HsPDA:

 -  Group A: experimental boluses of paracetamol at 15 mg/Kg four time a day for three
 consecutive days.

 -  Group B: standard boluses of ibuprofen at 10-5-5-mg/Kg/dose once a day for three
 consecutive days.

 The primary objective of the study is: to evaluate the efficacy of paracetamol versus
 standard ibuprofen regimen, by comparing the rate of ductal closure after the first and
 second course of pharmacological treatment. (PDA diagnosed by ECHO criteria)

 The secondary objective of the study is: to evaluate the safety of the above 2 therapeutic
 regimens in term of incidence of transient renal impairment, intraventricular hemorrhage
 (IVH) or other bleeding disorders, necrotizing enterocolitis (NEC) and isolated bowel
 perforation (without signs of NEC), incidence of sign of liver toxicity.
Inclusion Criteria:

 -  inborn neonates

 -  preterm neonates ≤ 31+ 6 days weeks gestation

 -  newborns with HsPDA

 -  parental written informed consent for participation in the study must be obtained

 Exclusion Criteria:

 -  Serum creatinine concentration greater than 1,5 mg/dl (132MMole/L)

 -  Urine output less than 1 ml/Kg/h

 -  Severe IVH (> grade II according to Volpe classification)

 -  Clinical bleeding tendency (as revealed by hematuria, blood in the gastric aspirate or
 in the stools, blood in the endotracheal tube aspirate)

 -  Necrotizing enterocolitis or marked abdominal distention with gastric bile residuals

 -  Thrombocyte count of less than 50.000/mm3

 -  Proved Sepsis

 -  Severe coagulopathy or liver failure

 -  Evidence of severe birth asphyxia, that is an APGAR score below 5 at 5 minutes of age
 and/or umbilical arterial pH < 7.0

 -  Known genetic or chromosomal disorders

 -  Participation in another clinical trial of any placebo, drug, biological, or device
 conducted under the provisions of a protocol.