Ductus Arteriosus Patent, Respiratory Distress Syndrome
Conditions
Keywords
Patent ductus arteriosus, Preterm infant, Paracetamol, Ibuprofen
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.
Interventions
15 mg/Kg every 6 hours for three days
10 -5-5 mg/Kg once a day for three days
Sponsors
University of Padova
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
36 Hours to 72 Hours
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| PDA pharmacological closure | Partecipants 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
| Measure | Time frame | Description |
|---|---|---|
| Oliguria | In the first 14 days of life | Rate of oliguria defined as a reduction on urine output less than 1ml/Kg/h, |
Other
| Measure | Time frame | Description |
|---|---|---|
| Necrotizing enterocolitis (NEC) | In the first 14 days of life | Rate of NEC in the paracetamol and ibuprofen group |
| Intraventricular haemorrhage (IVH) or death | Within 28 days of life | Rate of intraventricular haemorrhage (IVH) or death within 28 days of life (composite outcome). |
Countries
Italy
Outcome results
None listed