Paracetamol Versus Ibuprofen in Premature Infants With Hemodynamically Significant Patent Ductus Arteriosus

NCT04037514 | Completed Phase 3

• 1 other identifier: IBUPAR-TRIAL
• Study Type: interventional
• Target: 133
• Locations: 1 country
• Sites: 4

Brief Summary

Multicentric, double-blind clinical trial, which will evaluate the efficacy of iv paracetamol versus standard treatment with ibuprofen in the closure of patent ductus arteriosus in the preterm newborn. Secondarily, we intend to compare the safety of both treatments, increase our knowledge about the pharmacokinetics, pharmacodynamics and pharmacogenetics of paracetamol and ibuprofen in the neonatal period and make a pharmacoeconomic assessment of the use of both drugs.

Conditions

Patent Ductus Arteriosus After Premature Birth

Outcome Measures

Primary Outcomes (1)

• Rate of closure of the hsPDA after treatment with paracetamol (experimental drug) versus ibuprofen (control drug).

  It will include the closure rate after the first course of treatment, considered as ductus diameter \< 1 mm monitored by echocardiography performed by a pediatric cardiology specialist.

  24-48 hours after the completion of study intervention

Secondary Outcomes (16)

• Need for a second course of treatment

  from randomization until discharge, an average of 2 months

• Closure rate after two treatment courses

  from randomization until discharge, an average of 2 months

• Need for rescue treatment after two courses of treatment

  from randomization until discharge, an average of 2 months

• Reopening rate after closure

  from randomization until discharge, an average of 2 months

• Closing rate after reopening

  from randomization until discharge, an average of 2 months

Study Arms (2)

Paracetamol

EXPERIMENTAL

Intravenous paracetamol 15 mg/kg/6h for 3 or 6 days

Drug: Paracetamol

Ibuprofen

ACTIVE COMPARATOR

Intravenous ibuprofen 10 mg/kg/24 h (day 1) and 5 mg/kg/24h (day 2 and 3) for 3 or 6 days

Drug: Ibuprofen

Interventions

Paracetamol DRUG

Intravenous paracetamol 15 mg/kg/6h

Paracetamol

Ibuprofen DRUG

Intravenous ibuprofen 10 mg/kg/24h (day 1) and 5 mg/kg/24h (day 2 and 3)

Ibuprofen

Eligibility Criteria

• Age: Up to 14 Days
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Written Informed consent of parents/guardians
• Gestacional Age ≤30 weeks
• Postnatal age ≤ 2 weeks
• Need for ventilatory support
• Born in participating hospital/arrival to them within the period of application of the treatment
• st episode of hemodynamically significant Patent Ductus Arteriosus

You may not qualify if:

• Major congenital malformations or chromosomopathies
• Refusal to participate and / or sign the informed consent.
• Impossibility or erroneous randomization
• Participation in another clinical trial with drugs
• Diuresis less than 1 ml / kg / h for 8 h prior to treatment
• Greater than 1.8 mg / dl Creatinine
• Platelets below 50,000 / uL
• Active bleeding (tracheal, gastrointestinal and renal)
• Intraventricular hemorrhage recently (48h) (grades 3-4)
• Severe hyperbilirubinemia
• Liver failure or severe coagulopathy
• Active necrotizing enterocolitis or intestinal perforation
• Septic shock
• Imminent death

Sponsors & Collaborators

• Instituto de Investigacion Sanitaria La Fe: collaborator
• Spanish Clinical Research Network - SCReN: collaborator
• Máximo Vento Torres: lead

Study Sites (4)

Hospital Reina Sofía

Córdoba, Cordoba, Spain

Location

Hospital Universitario de Cabueñes

Gijón, Gijón, Spain

Location

Hospital Materno-Infantil (Hospital Regional Carlos Haya) Málaga:

Málaga, Málaga, Spain

Location

Hospital Universitari i Politècnic La Fe

Valencia, Valencia, 46026, Spain

Location

Related Publications (8)

• Dang D, Wang D, Zhang C, Zhou W, Zhou Q, Wu H. Comparison of oral paracetamol versus ibuprofen in premature infants with patent ductus arteriosus: a randomized controlled trial. PLoS One. 2013 Nov 4;8(11):e77888. doi: 10.1371/journal.pone.0077888. eCollection 2013.

  PMID: 24223740 BACKGROUND

• 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 BACKGROUND

• Oncel MY, Yurttutan S, Erdeve O, Uras N, Altug N, Oguz SS, Canpolat FE, Dilmen U. Oral paracetamol versus oral ibuprofen in the management of patent ductus arteriosus in preterm infants: a randomized controlled trial. J Pediatr. 2014 Mar;164(3):510-4.e1. doi: 10.1016/j.jpeds.2013.11.008. Epub 2013 Dec 18.

  PMID: 24359938 BACKGROUND

• Yang B, Gao X, Ren Y, Wang Y, Zhang Q. Oral paracetamol vs. oral ibuprofen in the treatment of symptomatic patent ductus arteriosus in premature infants: A randomized controlled trial. Exp Ther Med. 2016 Oct;12(4):2531-2536. doi: 10.3892/etm.2016.3676. Epub 2016 Sep 6.

  PMID: 27698754 BACKGROUND

• Dash SK, Kabra NS, Avasthi BS, Sharma SR, Padhi P, Ahmed J. Enteral paracetamol or Intravenous Indomethacin for Closure of Patent Ductus Arteriosus in Preterm Neonates: A Randomized Controlled Trial. Indian Pediatr. 2015 Jul;52(7):573-8. doi: 10.1007/s13312-015-0677-z.

  PMID: 26244949 BACKGROUND

• Sancak S, Gokmen Yildirim T, Topcuoglu S, Yavuz T, Karatekin G, Ovali F. Oral versus intravenous paracetamol: which is better in closure of patent ductus arteriosus in very low birth weight infants? J Matern Fetal Neonatal Med. 2016;29(1):135-9. doi: 10.3109/14767058.2014.989829. Epub 2014 Dec 23.

  PMID: 25471090 BACKGROUND

• El-Khuffash A, Jain A, Corcoran D, Shah PS, Hooper CW, Brown N, Poole SD, Shelton EL, Milne GL, Reese J, McNamara PJ. Efficacy of paracetamol on patent ductus arteriosus closure may be dose dependent: evidence from human and murine studies. Pediatr Res. 2014 Sep;76(3):238-44. doi: 10.1038/pr.2014.82. Epub 2014 Jun 18.

  PMID: 24941212 BACKGROUND

• Garcia-Robles A, Gimeno Navarro A, Serrano Martin MDM, Parraga Quiles MJ, Parra Llorca A, Poveda-Andres JL, Vento Torres M, Aguar Carrascosa M. Paracetamol vs. Ibuprofen in Preterm Infants With Hemodynamically Significant Patent Ductus Arteriosus: A Non-inferiority Randomized Clinical Trial Protocol. Front Pediatr. 2020 Jul 17;8:372. doi: 10.3389/fped.2020.00372. eCollection 2020.

  PMID: 32766181 DERIVED

MeSH Terms

Interventions

Acetaminophen; Ibuprofen

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids

Study Officials

• Maximo Vento Torres, PhD, MD

  Hospital Universitario La Fe

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Scientific Director Health Research Institute La Fe

Study Record Dates

• First Submitted: July 23, 2019
• First Posted: July 30, 2019
• Study Start: July 7, 2017
• Primary Completion: December 18, 2024
• Study Completion: December 18, 2024
• Last Updated: December 18, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

ES (4)