Paracetamol vs Ibuprofen for PDA Closure in Preterm Infants.

Respiratory Distress Syndrome Clinical Trial

— PARIDA  

Official title:

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

Clinical Trial Details — Status: Suspended

Administrative data

• NCT number: NCT02056223
• Other study ID #: PARIDA 01/2013
• Secondary ID: 2013-004955-19
• Status: Suspended
• Phase: Phase 2/Phase 3
• Start date: January 9, 2017
• Est. completion date: October 31, 2019

Study information

• Verified date: October 2019
• Source: University of Padua
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Suspended
• Enrollment: 120
• Est. completion date: October 31, 2019
• Est. primary completion date: October 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 72 Hours

Eligibility

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.

Related Conditions & MeSH terms

• Ductus Arteriosus Patent
• Ductus Arteriosus, Patent
• Respiratory Distress Syndrome
• Respiratory Distress Syndrome, Adult
• Respiratory Distress Syndrome, Newborn

Intervention

Drug:
• Intravenous paracetamol
15 mg/Kg every 6 hours for three days
• Intravenous ibuprofen
10 -5-5 mg/Kg once a day for three days

Locations

Country	Name	City	State
Italy	NICU, Women's and Children's Health Department, Azienda Ospedaliera-University of Padua	Padua

Sponsors (1)

Lead Sponsor	Collaborator
University of Padua

Country where clinical trial is conducted

Italy, 

References & Publications (4)

Allegaert K, Palmer GM, Anderson BJ. The pharmacokinetics of intravenous paracetamol in neonates: size matters most. Arch Dis Child. 2011 Jun;96(6):575-80. doi: 10.1136/adc.2010.204552. Epub 2011 Feb 13. — View Citation

Hammerman C, Bin-Nun A, Markovitch E, Schimmel MS, Kaplan M, Fink D. Ductal closure with paracetamol: a surprising new approach to patent ductus arteriosus treatment. Pediatrics. 2011 Dec;128(6):e1618-21. doi: 10.1542/peds.2011-0359. Epub 2011 Nov 7. — View Citation

Oncel MY, Yurttutan S, Degirmencioglu H, Uras N, Altug N, Erdeve O, Dilmen U. Intravenous paracetamol treatment in the management of patent ductus arteriosus in extremely low birth weight infants. Neonatology. 2013;103(3):166-9. doi: 10.1159/000345337. Ep — View Citation

Oncel MY, Yurttutan S, Uras N, Altug N, Ozdemir R, Ekmen S, Erdeve O, Dilmen U. An alternative drug (paracetamol) in the management of patent ductus arteriosus in ibuprofen-resistant or contraindicated preterm infants. Arch Dis Child Fetal Neonatal Ed. 20 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Necrotizing enterocolitis (NEC)	Rate of NEC in the paracetamol and ibuprofen group	In the first 14 days of life
Other	Intraventricular haemorrhage (IVH) or death	Rate of intraventricular haemorrhage (IVH) or death within 28 days of life (composite outcome).	Within 28 days of life
Primary	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	Oliguria	Rate of oliguria defined as a reduction on urine output less than 1ml/Kg/h,	In the first 14 days of life