Prophylaktische Behandlung des Ductus arteriosus bei Frühgeborenen durch Paracetamol

Punti finali primari (Fonte di dati: WHO)

Main Objective: Primary objectives :
Phase II: The objective of Phase II is to define the minimum effective dose of acetaminophen to close the ductus arteriosus before or at day 7 in preterm infants of 23-26 weeks of gestation

Phase III: The primary objective is an increase in surviving without severe morbidity at 36 weeks of post menstrual age (or at discharge if it occurs before) from 50% (placebo group) to 60% in group receiving a prophylactic treatment by acetaminophen during the first 5 days of life.;Secondary Objective: Secondary objectives :
Phase II:
? Tolerance of acetaminophen at each dose
? Pharmacokinetics of acetaminophen and evaluation of the concentration-response curve (i.e., acetaminophen exposure vs. time to close the ductus arteriosus or decrease the size of ductus).
? To evaluate the relationship between acetaminophen concentration and toxicity occurrence.

Phase III:
? Early prophylactic treatment by acetaminophen decreases pain score and opiate consumption during the first 5 days of life.
? Early prophylactic treatment by acetaminophen reduces the number of back-up treatment of PDA (NSAIDs, surgery, trans-catheter procedure)
? Early prophylactic treatment by acetaminophen reduces catecholamines, opioid and parenteral nutrition requirements
? Pharmacokinetics of acetaminophen (in 50 preterms).;Primary end point(s): Primary endpoint of phase II is the closure of Ductus Arteriosus (DA) assessed by echocardiography during the first 7 days of life, defined as DA closed at two consecutive echocardiographies or if the DA is closed at echocardiography of Day 7
Primary endpoint of phase III is the survival without severe morbidity at 36 weeks of post menstrual age or at first discharge home, whichever comes first. The severe morbidities include bronchopulmonary dysplasia (BPD Grade 3 according to NIH consensus), necrotizing enterocolitis (NEC) of Bell's stage II or III, intraventricular hemorrhage (IVH) grade III-IV or cystic leukomalacia observed at any time up to 36 weeks of post menstrual age.;Timepoint(s) of evaluation of this end point: Primary endpoint of phase II will be evaluate at day 7.

Primary endpoint of phase III is evaluate at 36 weeks of post menstrual age or at first discharge home.