NCT02422966

Brief Summary

The purpose of the study is to assess the efficacy and safety of paracetamol in comparison to ibuprofen in the treatment of patent ductus arteriosus (PDA) in preterm infants.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
110

participants targeted

Target at P50-P75 for phase_2

Timeline
Completed

Started Dec 2015

Typical duration for phase_2

Geographic Reach
1 country

5 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

April 9, 2015

Completed
13 days until next milestone

First Posted

Study publicly available on registry

April 22, 2015

Completed
7 months until next milestone

Study Start

First participant enrolled

December 1, 2015

Completed
3.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2019

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

April 1, 2019

Completed
Last Updated

July 12, 2019

Status Verified

July 1, 2019

Enrollment Period

3.1 years

First QC Date

April 9, 2015

Last Update Submit

July 11, 2019

Conditions

Ductus Arteriosus, Patent

Outcome Measures

Primary Outcomes (1)

  • success rate in closing PDA using paracetamol in comparison to ibuprofen.

    assessed echocardiographically.

    at Visit 3 (day 3).

Secondary Outcomes (11)

  • number of re-openings.

    at Follow-up 3 (day 30).

  • success rate in closing PDA after the second treatment course of ibuprofen as rescue medication.

    at Visit 6 (day 6).

  • success rate of closing PDA after the first day of the first treatment course.

    at Visit 1 (day 1).

  • success rate of closing PDA after the second day of the first treatment course.

    at Visit 2 (day 2).

  • incidence of surgical ligation.

    at Follow-up 3 (day 30).

  • +6 more secondary outcomes

Study Arms (2)

Paracetamol

EXPERIMENTAL

Paracetamol intravenous solution 15 mg/kg (corresponding to 1.5 ml/kg) per dose every 6 hours for 3 days, for a total amount of 12 doses.

Drug: Paracetamol

Ibuprofen

ACTIVE COMPARATOR

Ibuprofen intravenous solution at an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 5 mg/kg at 48 h.

Drug: Ibuprofen

Interventions

ParacetamolDRUG
Also known as: Acetaminophen
Paracetamol
IbuprofenDRUG
Ibuprofen

Eligibility Criteria

Age25 Weeks - 31 Weeks
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17)

You may qualify if:

  • Male or female preterm infants with no limitation of race.
  • Gestational age 25(+0) - 31(+6) weeks.
  • Age 24-72 hours.
  • Echocardiographic evidence of hemodynamically significant patent ductus arteriosus at the first 24-72 hours of life.
  • The diagnosis of hemodynamically significant PDA requiring treatment will be made by echocardiographic demonstration of a ductal left-to-right shunt, with a left atrium-to-aortic root ratio \>1.3 or a ductal size \>1.5 mm and excluding the cases in which the closing flow pattern suggests a restrictive PDA.
  • Willingness of the parents/legally authorized representative/child to sign the Consent Informed Form.

You may not qualify if:

  • Outborn patients.
  • Major congenital anomalies, including but not limited to congenital heart defects, Down syndrome newborn and/or new born suffering from congenital anomalies diagnosed during the fetal period.
  • Known positive HIV and/or known positive Hepatitis C Virus newborn's mother.
  • Life threatening infection, complicated or not by multiple organ dysfunction and failure syndrome.
  • Fetal hydrops.
  • Pulmonary hypertension diagnosed in the first 24-48 hours of life by means of heart ultrasound when the presence of a right-to-left shunt through the foramen ovale or ductus arteriosus is demonstrated, or when the estimated pulmonary pressure, in terms of the tricuspid regurgitation jet, is greater than two-thirds of the systemic arterial pressure.
  • Grade 3 or 4 intraventricular haemorrhage (IVH).
  • Urine output \<1 ml/kg of body weight/h during a 24 h collection period or urine output \<0.5 ml/kg of body weight/h in case it is measured at 24 hours of life of newborn.
  • Serum creatinine concentration \> 1.5 mg/dl (132 μmol/l).
  • Platelet count \< 50,000/mm3.
  • Major bleeding, as revealed by hematuria, or blood in the endotracheal aspirate, gastric aspirate, or stools, or consistent oozing of blood from puncture sites.
  • Severe liver failure, defined as elevated liver enzymes (ALT/Glutamate-Pyruvate Transaminase and Aspartate aminotransferase/GOT) \> 2 times the upper boundary of the normal range. For this kind of population the following normal ranges will be considered \[Rosenthal, 1997\]:
  • ALT/Glutamate-pyruvate transaminase: 6-50 U/L
  • Aspartate aminotransferase/GOT: 35-140 U/L
  • Medical need of administering other Nonsteroidal Antiinflammatory Drug (NSAID) different from ibuprofen.
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (5)

Azienda Ospedaliero Universitaria Careggi - Neonatologia e Terapia Intensiva Neonatale

Florence, 50134, Italy

Location

IRCCS "Giannina Gaslini" Genova - Patologia Neonatale e Terapia Intensiva Neonatale

Genova, 16147, Italy

Location

Fondazione IRCCS Cà Granda Ospedale Maggiore Policlinico U.O. di Neonatologia e Terapia Intensiva Neonatale

Milan, 20122, Italy

Location

Azienda Ospedaliera Istituti Clinici di Perfezionamento (ICP) - Ospedale dei Bambini "Vittore Buzzi" Milano - Neonatologia

Milan, 20154, Italy

Location

Policlinico Gemelli Roma - UOC Neonatologia

Roma, 00168, Italy

Location

Related Publications (3)

  • Jasani B, Mitra S, Shah PS. Paracetamol (acetaminophen) for patent ductus arteriosus in preterm or low birth weight infants. Cochrane Database Syst Rev. 2022 Dec 15;12(12):CD010061. doi: 10.1002/14651858.CD010061.pub5.

    PMID: 36519620DERIVED

  • Dani C, Lista G, Bianchi S, Mosca F, Schena F, Ramenghi L, Zecca E, Vento G, Poggi C, Leonardi V, Minghetti D, Rosignoli MT, Calisti F, Comandini A, Cattaneo A, Lipone P. Intravenous paracetamol in comparison with ibuprofen for the treatment of patent ductus arteriosus in preterm infants: a randomized controlled trial. Eur J Pediatr. 2021 Mar;180(3):807-816. doi: 10.1007/s00431-020-03780-8. Epub 2020 Sep 4.

    PMID: 32888085DERIVED

  • Dani C, Poggi C, Mosca F, Schena F, Lista G, Ramenghi L, Romagnoli C, Salvatori E, Rosignoli MT, Lipone P, Comandini A. Efficacy and safety of intravenous paracetamol in comparison to ibuprofen for the treatment of patent ductus arteriosus in preterm infants: study protocol for a randomized control trial. Trials. 2016 Apr 2;17:182. doi: 10.1186/s13063-016-1294-4.

    PMID: 27038924DERIVED

MeSH Terms

Conditions

Ductus Arteriosus, Patent

Interventions

AcetaminophenIbuprofen

Condition Hierarchy (Ancestors)

Heart Defects, CongenitalCardiovascular AbnormalitiesCardiovascular DiseasesHeart DiseasesCongenital AbnormalitiesCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

AcetanilidesAnilidesAmidesOrganic ChemicalsAniline CompoundsAminesPhenylpropionatesAcids, CarbocyclicCarboxylic Acids

Study Design

Study Type
interventional
Phase
phase 2
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

April 9, 2015

First Posted

April 22, 2015

Study Start

December 1, 2015

Primary Completion

January 1, 2019

Study Completion

April 1, 2019

Last Updated

July 12, 2019

Record last verified: 2019-07

Locations

IT(5)