Ductus Arteriosus PatentPhase 2/3PARIDANCT02056223
Paracetamol vs Ibuprofen for PDA Closure in Preterm Infants.
A Phase 2/3 study testing Intravenous paracetamol and Intravenous ibuprofen in people with Ductus Arteriosus Patent and Respiratory Distress Syndrome, run by University of Padova at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 36 to 72 hours
- Conditions the study is for
- Ductus Arteriosus Patent, Respiratory Distress Syndrome
- What is being tested?
- Intravenous paracetamol and Intravenous ibuprofen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 120 participants
- Where
- 1 siteItaly
- Study dates
- 9 Jan 2017to 31 Oct 2019
- Phase
- Phase 2/3
- 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 36 to 72 hours
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- inborn neonates
- preterm neonates ≤ 31+ 6 days weeks gestation
- newborns with HsPDA
- parental written informed consent for participation in the study must be obtained
Who cannot join
- 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
Show all 11Show fewer
- 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.
Trial locations and contacts
1 site in 1 country.
Italy1 site
NICU, Women's and Children's Health Department, Azienda Ospedaliera-University of Padua
Padua, 35128
About this study
Official title: Paracetamol Versus Ibuprofen for Patent Ductus Arteriosus Closure in Preterm Infants. A Prospective, Randomized, Controlled, Double Blind, Multicenter Clinical Trial.
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.
Read the detailed description
The objective of this trial is to compare the efficacy and safety of 2 therapeutic regimens for PDA treatment in a population of preterm newborns of gestational age (GA) <31+6 weeks with respiratory distress syndrome (RDS) and HsPDA:
- Group A: experimental boluses of paracetamol at 15 mg/Kg four time a day for three consecutive days.
- Group B: standard boluses of ibuprofen at 10-5-5-mg/Kg/dose once a day for three consecutive days.
The primary objective of the study is: to evaluate the efficacy of paracetamol versus standard ibuprofen regimen, by comparing the rate of ductal closure after the first and second course of pharmacological treatment. (PDA diagnosed by ECHO criteria)
The secondary objective of the study is: to evaluate the safety of the above 2 therapeutic regimens in term of incidence of transient renal impairment, intraventricular hemorrhage (IVH) or other bleeding disorders, necrotizing enterocolitis (NEC) and isolated bowel perforation (without signs of NEC), incidence of sign of liver toxicity.
- Being tested
- Intravenous paracetamol, Intravenous ibuprofen
- Keywords
- Patent ductus arteriosus, Preterm infant, Paracetamol, Ibuprofen
- Medical subject headings
- Ductus Arteriosus, Patent, Respiratory Distress Syndrome, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Intravenous paracetamolDrug
Also called Paracetamol i.v.
15 mg/Kg every 6 hours for three days
Intravenous ibuprofenDrug
Also called Pedea i.v.
10 -5-5 mg/Kg once a day for three days
| Study group | Role | What they receive |
|---|---|---|
| paracetamol | Experimental | Boluses of intravenous paracetamol at 15 mg/Kg four time a day for three consecutive days. Receives: 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. Receives: Drug: Intravenous ibuprofen |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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
Rate of oliguria defined as a reduction on urine output less than 1ml/Kg/h,
Measured: In the first 14 days of life
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Feb 2014 (estimated)
- Study start9 Jan 2017
- Primary completion31 Oct 2019 (estimated)
- Study completion31 Oct 2019 (estimated)
Why it stopped: We enrolled only 53 patients
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Ductus Arteriosus PatentStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University of Padova
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Paola Lago, University of Padova
- Investigators
- Paola Lago, MD, Principal investigator, Women's and Children's Health Department- AO- University of Padua
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02056223
- Sponsor's protocol ID
- PARIDA 01/2013
- Other IDs
- 2013-004955-19
- Acronym
- PARIDA
- Status last verified
- Oct 2019
- First submitted
- 3 Feb 2014
- Last updated
- 4 Nov 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 23258386Hammerman 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.
PubMed 22065264Oncel 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.
PubMed 22611117Allegaert 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.
PubMed 21317433
Study at a glance
From the registry record, last updated by the sponsor on 4 Nov 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Paracetamol Versus Ibuprofen for Patent Ductus Arteriosus Closure in Preterm Infants. A Prospective, Randomized, Controlled, Double Blind, Multicenter Clinical Trial.
- ClinicalTrials.gov ID
- NCT02056223
- Acronym / sponsor ID
- PARIDA / PARIDA 01/2013
- Keywords
- Patent ductus arteriosus, Preterm infant, Paracetamol, Ibuprofen
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- SuspendedReason stopped: We enrolled only 53 patients
- Enrolment
- 120 participants (estimated)
- Lead sponsor
- University of PadovaUniversity, hospital or other
- Study start
- 9 Jan 2017 (actual)
- Primary completion
- 31 Oct 2019 (estimated)
- Study completion
- 31 Oct 2019 (estimated)
- First posted
- 5 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
The objective of this trial is to compare the efficacy and safety of 2 therapeutic regimens for PDA treatment in a population of preterm newborns of gestational age (GA) <31+6 weeks with respiratory distress syndrome (RDS) and HsPDA:
- Group A: experimental boluses of paracetamol at 15 mg/Kg four time a day for three consecutive days.
- Group B: standard boluses of ibuprofen at 10-5-5-mg/Kg/dose once a day for three consecutive days.
The primary objective of the study is: to evaluate the efficacy of paracetamol versus standard ibuprofen regimen, by comparing the rate of ductal closure after the first and second course of pharmacological treatment. (PDA diagnosed by ECHO criteria)
The secondary objective of the study is: to evaluate the safety of the above 2 therapeutic regimens in term of incidence of transient renal impairment, intraventricular hemorrhage (IVH) or other bleeding disorders, necrotizing enterocolitis (NEC) and isolated bowel perforation (without signs of NEC), incidence of sign of liver toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| paracetamol | Experimental | Drug: Intravenous paracetamolBoluses of intravenous paracetamol at 15 mg/Kg four time a day for three consecutive days. |
| Intravenous ibuprofen | Active comparator | Drug: Intravenous ibuprofenStandard boluses of ibuprofen at 10-5-5-mg/Kg/dose once a day for three consecutive days. |
Who may qualify
- Ages
- 36 to 72 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- inborn neonates
- preterm neonates ≤ 31+ 6 days weeks gestation
- newborns with HsPDA
- parental written informed consent for participation in the study must be obtained
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Intravenous paracetamolAlso: Paracetamol i.v.15 mg/Kg every 6 hours for three days | Drug | paracetamol |
| Intravenous ibuprofenAlso: Pedea i.v.10 -5-5 mg/Kg once a day for three days | Drug | Intravenous ibuprofen |
Primary outcome
PDA pharmacological closure
Time frame: Partecipants will be evaluated at the end of first and second course, at an expected avarage of 8 days of life (DOL)
The rate of ductal closure after the first and second course of pharmacological treatment. (PDA diagnosed by ECHO criteria) in paracetamol versus ibuprofen group
1 secondary outcome
Oliguria
Time frame: In the first 14 days of life
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Nov 2019.
- Results publication: PubMed 23258386Oncel 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.
- Results publication: PubMed 22065264Hammerman 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.
- Results publication: PubMed 22611117Oncel 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.
- Results publication: PubMed 21317433Allegaert 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Paola Lago, MD principal investigator
Women's and Children's Health Department- AO- University of Padua
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing Intravenous paracetamol and Intravenous ibuprofen in people with Ductus Arteriosus Patent and Respiratory Distress Syndrome, run by University of Padova at 1 site 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 4 inclusion and 11 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: paused, as of the sponsor's last update on 4 Nov 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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 combined 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.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
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?
PDA pharmacological closure (time frame: Partecipants will be evaluated at the end of first and second course, at an expected avarage of 8 days of life (DOL)). 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 NCT02056223, which also lists 4 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 4 Nov 2019.