Paracetamol vs Ibuprofen for PDA Closure in Preterm Infants.

Study Overview
=================
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.

Official Title
-----------------
Paracetamol Versus Ibuprofen for Patent Ductus Arteriosus Closure in Preterm Infants. A Prospective, Randomized, Controlled, Double Blind, Multicenter Clinical Trial.

Conditions
-----------------
Ductus Arteriosus Patent, Respiratory Distress Syndrome

Intervention / Treatment
-----------------
* Drug: Intravenous paracetamol
* Drug: Intravenous ibuprofen


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 36 Hours
Maximum Age: 72 Hours

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: paracetamol<br>Boluses of intravenous paracetamol at 15 mg/Kg four time a day for three consecutive days. | Drug: Intravenous paracetamol<br>* 15 mg/Kg every 6 hours for three days<br>* Other names: Paracetamol i.v.;|
| Active Comparator: Intravenous ibuprofen<br>Standard boluses of ibuprofen at 10-5-5-mg/Kg/dose once a day for three consecutive days. | Drug: Intravenous ibuprofen<br>* 10 -5-5 mg/Kg once a day for three days<br>* Other names: Pedea i.v.;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PDA pharmacological closure | The rate of ductal closure after the first and second course of pharmacological treatment. (PDA diagnosed by ECHO criteria) in paracetamol versus ibuprofen group | Partecipants will be evaluated at the end of first and second course, at an expected avarage of 8 days of life (DOL) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Oliguria | Rate of oliguria defined as a reduction on urine output less than 1ml/Kg/h, | In the first 14 days of life | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Patent ductus arteriosus, Preterm infant, Paracetamol, Ibuprofen