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Paracetamol vs Ibuprofen for PDA Closure in Preterm Infants.

Phase 2
Suspended
Conditions
Respiratory Distress Syndrome
Ductus Arteriosus Patent
Interventions
Registration Number
NCT02056223
Lead Sponsor
University of Padova
Brief Summary

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.

Detailed Description

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.

Recruitment & Eligibility

Status
SUSPENDED
Sex
All
Target Recruitment
120
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Intravenous ibuprofenIntravenous ibuprofenStandard boluses of ibuprofen at 10-5-5-mg/Kg/dose once a day for three consecutive days.
paracetamolIntravenous paracetamolBoluses of intravenous paracetamol at 15 mg/Kg four time a day for three consecutive days.
Primary Outcome Measures
NameTimeMethod
PDA pharmacological closurePartecipants will be evaluated at the end of first and second course, at an expected avarage of 8 days of life (DOL)

The rate of ductal closure after the first and second course of pharmacological treatment. (PDA diagnosed by ECHO criteria) in paracetamol versus ibuprofen group

Secondary Outcome Measures
NameTimeMethod
OliguriaIn the first 14 days of life

Rate of oliguria defined as a reduction on urine output less than 1ml/Kg/h,

Trial Locations

Locations (1)

NICU, Women's and Children's Health Department, Azienda Ospedaliera-University of Padua

🇮🇹

Padua, Italy

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