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

NCT ID: NCT04037514

Last Updated: 2025-12-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE3

Total Enrollment

133 participants

Study Classification

INTERVENTIONAL

Study Start Date

2017-07-07

Study Completion Date

2024-12-18

Brief Summary

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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.

Detailed Description

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Those newborns ≤ 30 weeks of gestational age who are diagnosed in the first 2 weeks of hemodynamically significant ductus arteriosus and who do not meet any exclusion criteria will be eligible to participate in the study.

The PARACETAMOL group will receive intravenous doses of 15 mg/kg administered every 6h for 3 days (up to a maximum of 2 courses, i.e. 6 days). The IBUPROFEN group (control group) will receive the usual treatment, this is an initial dose of 10 mg/kg followed by 5 mg/kg intravenously at 24 and 48 hours after the first (all three doses are considered a treatment course), up a maximum of 2 courses).

A daily echocardiographic control will be performed to evaluate the closure of the ductus. If the ductus remains open and with significant clinical repercussion after completing a 3-day course of treatment, another batch of 3 doses of the same treatment will be administered. If medical treatment fails after two courses (6 days), the possibility of administering a batch of Ibuprofen at usual doses in both groups with the intention of offering standard treatment to all patients will be considered. Once the medical treatment with both drugs is completed if the ductus remains significant, the surgical closure will be carried out.

Conditions

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Patent Ductus Arteriosus After Premature Birth

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

QUADRUPLE

Participants Caregivers Investigators Outcome Assessors

Study Groups

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Paracetamol

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

Group Type EXPERIMENTAL

Paracetamol

Intervention Type DRUG

Intravenous paracetamol 15 mg/kg/6h

Ibuprofen

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

Group Type ACTIVE_COMPARATOR

Ibuprofen

Intervention Type DRUG

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

Interventions

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Paracetamol

Intravenous paracetamol 15 mg/kg/6h

Intervention Type DRUG

Ibuprofen

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

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

* 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
* 1 st episode of hemodynamically significant Patent Ductus Arteriosus

Exclusion Criteria

* 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
Maximum Eligible Age

14 Days

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Instituto de Investigacion Sanitaria La Fe

OTHER

Sponsor Role collaborator

Spanish Clinical Research Network - SCReN

NETWORK

Sponsor Role collaborator

Máximo Vento Torres

OTHER

Sponsor Role lead

Responsible Party

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Máximo Vento Torres

Scientific Director Health Research Institute La Fe

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Maximo Vento Torres, PhD, MD

Role: STUDY_CHAIR

Hospital Universitario La Fe

Locations

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Hospital Reina Sofía

Córdoba, Cordoba, Spain

Site Status

Hospital Universitario de Cabueñes

Gijón, Gijón, Spain

Site Status

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

Málaga, Málaga, Spain

Site Status

Hospital Universitari i Politècnic La Fe

Valencia, Valencia, Spain

Site Status

Countries

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Spain

References

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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.

Reference Type BACKGROUND
PMID: 24223740 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22065264 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24359938 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 27698754 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 26244949 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 25471090 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 24941212 (View on PubMed)

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.

Reference Type DERIVED
PMID: 32766181 (View on PubMed)

Other Identifiers

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IBUPAR-TRIAL

Identifier Type: -

Identifier Source: org_study_id