Paracetamol vs Ibuprofen for PDA Closure in Preterm Infants.

NCT02056223 | Suspended Phase 2 DMC

• 2 other identifiers: PARIDA 01/20132013-004955-19
• Study Type: interventional
• Target: 120
• Locations: 1 country
• Sites: 1

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.

Conditions

Ductus Arteriosus Patent; Respiratory Distress Syndrome

Keywords

Patent ductus arteriosus; Preterm infant; Paracetamol; Ibuprofen

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Oliguria

  In the first 14 days of life

Other Outcomes (2)

• Necrotizing enterocolitis (NEC)

  In the first 14 days of life

• Intraventricular haemorrhage (IVH) or death

  Within 28 days of life

Study Arms (2)

paracetamol

EXPERIMENTAL

Boluses of intravenous paracetamol at 15 mg/Kg four time a day for three consecutive days.

Drug: Intravenous paracetamol

Intravenous ibuprofen

ACTIVE COMPARATOR

Standard boluses of ibuprofen at 10-5-5-mg/Kg/dose once a day for three consecutive days.

Drug: Intravenous ibuprofen

Interventions

Intravenous paracetamol DRUG

15 mg/Kg every 6 hours for three days

Also known as: Paracetamol i.v.

paracetamol

Intravenous ibuprofen DRUG

10 -5-5 mg/Kg once a day for three days

Also known as: Pedea i.v.

Intravenous ibuprofen

Eligibility Criteria

• Age: 36 Hours - 72 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• inborn neonates
• preterm neonates ≤ 31+ 6 days weeks gestation
• newborns with HsPDA
• parental written informed consent for participation in the study must be obtained

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of Padova: lead

Study Sites (1)

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

Padua, 35128, Italy

Location

Related Publications (4)

• 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. Epub 2012 Dec 19.

  PMID: 23258386 RESULT

• 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.

  PMID: 22065264 RESULT

• 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. 2013 Jan;98(1):F94. doi: 10.1136/archdischild-2012-302044. Epub 2012 May 18. No abstract available.

  PMID: 22611117 RESULT

• 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.

  PMID: 21317433 RESULT

MeSH Terms

Conditions

Ductus Arteriosus, Patent; Respiratory Distress Syndrome; Premature Birth

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Obstetric Labor, Premature; Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases

Study Officials

• Paola Lago, MD

  Women's and Children's Health Department- AO- University of Padua

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD

Study Record Dates

• First Submitted: February 3, 2014
• First Posted: February 5, 2014
• Study Start: January 9, 2017
• Primary Completion: October 31, 2019
• Study Completion: October 31, 2019
• Last Updated: November 4, 2019

Record last verified: 2019-10

Locations

IT (1)