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Ductus Arteriosus, PatentPhase 2NCT02422966

Paracetamol in Patent Ductus Arteriosus

A Phase 2 study testing Paracetamol and Ibuprofen in people with Ductus Arteriosus, Patent, run by Aziende Chimiche Riunite Angelini Francesco S.p.A at 5 sites in Italy.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 25 to 31 weeks
Conditions the study is for
Ductus Arteriosus, Patent
What is being tested?
Paracetamol and Ibuprofen
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
110 participants
Where
5 sitesItaly
Study dates
Dec 2015to Apr 2019
Phase
Phase 2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 25 to 31 weeks
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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.
  • Participation to another trial involving any investigational drug.

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Italy5 sites

  • Azienda Ospedaliero Universitaria Careggi - Neonatologia e Terapia Intensiva Neonatale

    Florence, 50134

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

    Genova, 16147

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

    Milan, 20122

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

    Milan, 20154

  • Policlinico Gemelli Roma - UOC Neonatologia

    Roma, 00168

Other trials in Italy

About this study

Official title: Efficacy and Safety of Paracetamol in Comparison to Ibuprofen for Patent Ductus Arteriosus Treatment in Preterm Infants: A Randomized, Open Label, Comparator-controlled, Prospective Study

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.

Read the detailed description

Although patency of the ductus arteriosus is essential for fetal circulation, the postnatal ductal closure is critical for postnatal circulatory adaptation. In premature infants the circulating prostaglandin levels are higher than at term, and respiratory difficulties may lead to a state of hypoxia, which contribute to the failure of the ductus closure. Recently, an incidental finding in one preterm infant led to look at paracetamol, one of the most common drugs available, as an alternative therapeutic approach to ductal closure. If paracetamol is proven to be effective, it could become the treatment of choice for the management of PDA, mainly due to its more favorable safety profile.

Although the recent results available in the literature demonstrates an highly success rate in ductal closure with paracetamol, all case studies are not powered to show efficacy of paracetamol for PDA closure. Further prospective randomized-controlled trials are needed to evaluate the efficacy of paracetamol versus ibuprofen for the closure of PDA.

If paracetamol is indeed proven to be effective, it could become the treatment of choice for the management of PDA, mainly due to its more favorable side effect profile. In order to test this hypothesis, a randomized, open label, parallel groups, comparator controlled, multicentre, prospective study is proposed.

Being tested
Paracetamol, Ibuprofen
Medical subject headings
Ductus Arteriosus, Patent

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • ParacetamolDrug

    Also called Acetaminophen

  • IbuprofenDrug

Study groups in NCT02422966
Study groupRoleWhat they receive
ParacetamolExperimentalParacetamol 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.
Receives: Drug: Paracetamol
IbuprofenActive comparatorIbuprofen intravenous solution at an initial dose of 10 mg/kg, followed by 5 mg/kg at 24 and 5 mg/kg at 48 h.
Receives: Drug: Ibuprofen

What is being measured

The primary outcome is the main question the study is designed to answer.

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

    assessed echocardiographically.

    Measured: at Visit 3 (day 3).

Secondary outcomes (11)

  1. number of re-openings.

    assessed echocardiographically.

    Measured: at Follow-up 3 (day 30).

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

    assessed echocardiographically.

    Measured: at Visit 6 (day 6).

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

    assessed echocardiographically.

    Measured: at Visit 1 (day 1).

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

    assessed echocardiographically.

    Measured: at Visit 2 (day 2).

  5. incidence of surgical ligation.

    Measured: at Follow-up 3 (day 30).

  6. incidence of renal failure, liver failure and gastrointestinal complications (including isolated intestinal perforation).

    assessed by laboratory analysis.

    Measured: at Follow-up 3 (day 30).

  7. incidence of death,

    Measured: at Follow-up 3 (day 30).

  8. incidence of death.

    Measured: at Follow-up 4 (40 weeks post-conception).

  9. incidence of sepsis.

    Measured: at Follow-up 3 (day 30).

  10. hospital-stay duration in Neonatal Intensive Care Unit.

    Measured: at Follow-up 4 (40 weeks post-conception).

  11. occurrence of adverse effects.

    Measured: at Follow-up 3 (day 30).

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Apr 2015 (estimated)
  2. Study startDec 2015
  3. Primary completionJan 2019
  4. Study completionApr 2019

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
110 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02422966
Sponsor's protocol ID
044CF13273
Status last verified
Jul 2019
First submitted
9 Apr 2015
Last updated
12 Jul 2019
Results posted
No
Data monitoring committee
No

Publications

  • 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.

    PubMed 36519620

  • 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.

    PubMed 32888085

  • 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.

    PubMed 27038924

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Paracetamol and Ibuprofen in people with Ductus Arteriosus, Patent, run by Aziende Chimiche Riunite Angelini Francesco S.p.A at 5 sites in Italy.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 16 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 12 Jul 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

success rate in closing PDA using paracetamol in comparison to ibuprofen. (time frame: at Visit 3 (day 3).). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02422966, which also lists 3 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Jul 2019.

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Paracetamol in Patent Ductus Arteriosus (NCT02422966) | AzTrials