Patent Ductus ArteriosusPhase 1PAINCT03648437
Paracetamol And Ibuprofen/Indomethacin in Closing Patent Ductus Arteriosus
A Phase 1 study testing Paracetamol 10Mg/mL, 0.45% Sodium Chloride and Ibuprofen in people with Patent Ductus Arteriosus, run by University of Oulu at 4 sites in Finland.
Trial summary
The purpose of this pilot trial is to study efficacy and safety of simultaneous intravenous (iv) ibuprofen/indomethacin and paracetamol medications in the closure of patent ductus arteriosus (PDA) in preterm infants. It is randomized, placebo-controlled, double-blind, phase 1, multicenter, clinical trial. Read more about this study
- Who is it for?
- Ages Up to 4 months
- Conditions the study is for
- Patent Ductus Arteriosus
- What is being tested?
- Paracetamol 10Mg/mL, 0.45% Sodium Chloride and Ibuprofen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 22 participants
- Where
- 4 sitesFinland
- Study dates
- 3 Sep 2018to 4 Oct 2024
- Phase
- Phase 1
- 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 Up to 4 months
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Preterm infants (born before 37+0 gestation weeks) who are diagnosed to have a hemodynamically significant PDA and who, according to the decision of the attending clinician, need ibuprofen therapy, are eligible to this trial.
Who cannot join
- severe malformation or suspected chromosomal defect
- other very severe life-threatening disease (e.g. very severe birth asphyxia or persistent pulmonary hypertension, etc.)
Trial locations and contacts
4 sites in 1 country.
Finland4 sites
Helsinki Univeristy Central Hospital
Helsinki
Department of Pediatrics, Oulu University Hospital
Oulu, 90014
Tampere University Hospital
Tampere
Turku University Hospital
Turku
About this study
Official title: Paracetamol And Ibuprofen/Indomethacin in Closing Patent Ductus Arteriosus of Preterm Infants - Randomised, Placebo-controlled Multicentre Trial
The purpose of this pilot trial is to study efficacy and safety of simultaneous intravenous (iv) ibuprofen/indomethacin and paracetamol medications in the closure of patent ductus arteriosus (PDA) in preterm infants. It is randomized, placebo-controlled, double-blind, phase 1, multicenter, clinical trial.
Read the detailed description
Premature infants (born before 37 weeks gestational age) with patent ductus arteriosus (PDA) are the focus of the study since no trials on the additive efficacy of these two medications on the contraction of ductus arteriosus are available. Preterm infants who are diagnosed to have a hemodynamically significant PDA and who, according to the decision of the attending clinician, need ibuprofen/indomethacin therapy, are eligible to this trial.
If the parents deny the consent, the patient will be treated according to the standard PDA treatment: three days' iv ibuprofen Pedea® 5mg/ml solution infusion (Oulu, Helsinki, Tartu) dosing: 10mg/kg + 5mg/kg + 5mg/kg (q24h); or three days' iv indomethacin (Turku) 0.2mg/kg + 0.1mg/kg + 0.1mg/kg (q24h). In case of any contraindications for ibuprofen/indomethacin, the treatment would be surgical ligation.
- Conditions
- Patent Ductus Arteriosus
- Being tested
- Paracetamol 10Mg/mL, 0.45% Sodium Chloride, Ibuprofen, Indomethacin
- Keywords
- acetaminophen, ibuprofen, preterm infant, near infra-red spectroscopy, indomethacin
- Medical subject headings
- Ductus Arteriosus, Patent, Premature Birth
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Paracetamol 10Mg/mLDrug
Also called Paracetamol Fresenius Kabi 10mg/mL infusion solution
Experimental drug
0.45% Sodium ChlorideDrug
Also called NATRIUMKLORID BRAUN 4,5 mg/mL infusion solution
Placebo comparator
IbuprofenDrug
Also called Pedea 5mg/mL injection solution
Standard therapy
IndomethacinDrug
Also called Liometacen 50mg/2mL injection
Standard therapy
| Study group | Role | What they receive |
|---|---|---|
| Pedea 5mg/mL and Paracetamol 10mg/mL | Experimental | Intravenous (IV) ibuprofen 5mg/mL q 24h for 3 days, dosages: 10mg/kg + 5mg/kg + 5mg/kg and IV paracetamol 10mg/mL for 3 days: loading dose 20mg/kg, following 7.5mg/kg q 6h (up to12 doses) Receives: Drug: Paracetamol 10Mg/mL; Drug: Ibuprofen |
| Pedea 5mg/mL and 0.45 sodium chloride | Placebo comparator | IV ibuprofen 5mg/mL q 24h for 3 days, dosages: 10mg/kg + 5mg/kg + 5mg/kg and NaCl 0.45% for 3 days, the same amount in mL as would have been given IV paracetamol Receives: Drug: 0.45% Sodium Chloride; Drug: Ibuprofen |
| Indomethacin 25mg/mL and Paracetamol10mg/mL | Experimental | Intravenous (IV) indometahcin 25mg/mL q 24h for 3 days, dosages: 0.2mg/kg + 0.1mg/kg + 0.1mg/kg and IV paracetamol 10mg/mL for 3 days: loading dose 20mg/kg, following 7.5mg/kg q 6h (up to12 doses) Receives: Drug: Paracetamol 10Mg/mL; Drug: Indomethacin |
| Indomethacin 25mg/mL and 0.45 sodium chloride | Placebo comparator | Intravenous (IV) indomethacin 25mg/mL q 24h for 3 days, dosages: 0.2mg/kg + 0.1mg/kg + 0.1mg/kg and NaCl 0.45% for 3 days, the same amount in mL as would have been given IV paracetamol Receives: Drug: 0.45% Sodium Chloride; Drug: Indomethacin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Ductal closure
Number of patients with ductal contraction without need for other PDA therapies
Measured: Neonatal internsive care unit (NICU) stay up to 12 weeks
Secondary outcomes (7)
Need for ductal therapies
Given ductal therapies after the study drug
Measured: NICU stay up to 12 weeks
Cardiac ultrasound findings
Ductal caliber (mm, mm/kg), LA/Ao ratio
Measured: NICU stay up to 12 weeks
Duration of any ventilation assist
The ventilation assist time pediod
Measured: NICU stay up to 12 weeks
Paracetamol serum levels
Measured paracetamol concentrations (mg/mL)
Measured: Study drug period up to 4 days
Paracetamol side effects
Observed adverse events linked to study drug
Measured: Study drug period plus 7 days, up to 10 days
Long term complications of prematurity
Moderate-to-severe bronchopulmonary dysplasia, intraventricular hemorrhage grade 2-4, moderate to severe necrotizing enterocolitis, retinopathy of prematurity needing therapy
Measured: Hospital stay up to 18 weeks
Other long-term morbidity, and mortality
Other severe diseases
Measured: Hospital stay up to 18 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Aug 2018
- Study start3 Sep 2018
- Primary completion4 Oct 2024
- Study completion4 Oct 2024
Why it stopped: The PDA patients have vanished. The last recruitment took place in 2022. In the joint discussion of the principal researchers, it was concluded that PDA patients no longer have to be treated in Finland and the study was terminated.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Patent Ductus ArteriosusStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- multicenter, randomized, placebo-controlled, double-blind, clinical trial
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 22 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oulu
- Sponsor type
- University, hospital or other
- Collaborators
- Helsinki University Central Hospital, Turku University Hospital, Tampere University Hospital
- Responsible party
- Principal investigator, Outi Aikio, University of Oulu
- Investigators
- Outi Aikio, MD, PhD, Principal investigator, Oulu Univerisity Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03648437
- Sponsor's protocol ID
- 38/2018
- Acronym
- PAI
- Status last verified
- Oct 2024
- First submitted
- 23 Aug 2018
- Last updated
- 18 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Harkin P, Harma A, Aikio O, Valkama M, Leskinen M, Saarela T, Hallman M. Paracetamol Accelerates Closure of the Ductus Arteriosus after Premature Birth: A Randomized Trial. J Pediatr. 2016 Oct;177:72-77.e2. doi: 10.1016/j.jpeds.2016.04.066. Epub 2016 May 20.
PubMed 27215779Juujarvi S, Saarela T, Hallman M, Aikio O. Intravenous paracetamol was associated with closure of the ductus arteriosus in extremely premature infants. Acta Paediatr. 2018 Apr;107(4):605-610. doi: 10.1111/apa.14137. Epub 2017 Nov 17.
PubMed 29105147Harma A, Aikio O, Hallman M, Saarela T. Intravenous Paracetamol Decreases Requirements of Morphine in Very Preterm Infants. J Pediatr. 2016 Jan;168:36-40. doi: 10.1016/j.jpeds.2015.08.003. Epub 2015 Aug 29.
PubMed 26323200Aikio O, Harkin P, Saarela T, Hallman M. Early paracetamol treatment associated with lowered risk of persistent ductus arteriosus in very preterm infants. J Matern Fetal Neonatal Med. 2014 Aug;27(12):1252-6. doi: 10.3109/14767058.2013.854327. Epub 2013 Oct 31.
PubMed 24111688Juujarvi S, Kallankari H, Patsi P, Leskinen M, Saarela T, Hallman M, Aikio O. Follow-up study of the early, randomised paracetamol trial to preterm infants, found no adverse reactions at the two-years corrected age. Acta Paediatr. 2019 Mar;108(3):452-458. doi: 10.1111/apa.14614. Epub 2018 Nov 12.
PubMed 30325529
Study at a glance
From the registry record, last updated by the sponsor on 18 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Paracetamol And Ibuprofen/Indomethacin in Closing Patent Ductus Arteriosus of Preterm Infants - Randomised, Placebo-controlled Multicentre Trial
- ClinicalTrials.gov ID
- NCT03648437
- Acronym / sponsor ID
- PAI / 38/2018
- Conditions
- Patent Ductus Arteriosus
- Keywords
- acetaminophen, ibuprofen, preterm infant, near infra-red spectroscopy, indomethacin
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The PDA patients have vanished. The last recruitment took place in 2022. In the joint discussion of the principal researchers, it was concluded that PDA patients no longer have to be treated in Finland and the study was terminated.
- Enrolment
- 22 participants (actual)
- Lead sponsor
- University of OuluUniversity, hospital or other
- Collaborators
- Helsinki University Central Hospital, Turku University Hospital, Tampere University Hospital
- Study start
- 3 Sep 2018 (actual)
- Primary completion
- 4 Oct 2024 (actual)
- Study completion
- 4 Oct 2024 (actual)
- First posted
- 27 Aug 2018 (actual)
- 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.
The purpose of this pilot trial is to study efficacy and safety of simultaneous intravenous (iv) ibuprofen/indomethacin and paracetamol medications in the closure of patent ductus arteriosus (PDA) in preterm infants. It is randomized, placebo-controlled, double-blind, phase 1, multicenter, clinical trial.
Detailed description
Premature infants (born before 37 weeks gestational age) with patent ductus arteriosus (PDA) are the focus of the study since no trials on the additive efficacy of these two medications on the contraction of ductus arteriosus are available. Preterm infants who are diagnosed to have a hemodynamically significant PDA and who, according to the decision of the attending clinician, need ibuprofen/indomethacin therapy, are eligible to this trial.
If the parents deny the consent, the patient will be treated according to the standard PDA treatment: three days' iv ibuprofen Pedea® 5mg/ml solution infusion (Oulu, Helsinki, Tartu) dosing: 10mg/kg + 5mg/kg + 5mg/kg (q24h); or three days' iv indomethacin (Turku) 0.2mg/kg + 0.1mg/kg + 0.1mg/kg (q24h). In case of any contraindications for ibuprofen/indomethacin, the treatment would be surgical ligation.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 4
- Model description
- multicenter, randomized, placebo-controlled, double-blind, clinical trial
| Arm | Type | Receives |
|---|---|---|
| Pedea 5mg/mL and Paracetamol 10mg/mL | Experimental | Drug: Paracetamol 10Mg/mL, Drug: IbuprofenIntravenous (IV) ibuprofen 5mg/mL q 24h for 3 days, dosages: 10mg/kg + 5mg/kg + 5mg/kg and IV paracetamol 10mg/mL for 3 days: loading dose 20mg/kg, following 7.5mg/kg q 6h (up to12 doses) |
| Pedea 5mg/mL and 0.45 sodium chloride | Placebo comparator | Drug: 0.45% Sodium Chloride, Drug: IbuprofenIV ibuprofen 5mg/mL q 24h for 3 days, dosages: 10mg/kg + 5mg/kg + 5mg/kg and NaCl 0.45% for 3 days, the same amount in mL as would have been given IV paracetamol |
| Indomethacin 25mg/mL and Paracetamol10mg/mL | Experimental | Drug: Paracetamol 10Mg/mL, Drug: IndomethacinIntravenous (IV) indometahcin 25mg/mL q 24h for 3 days, dosages: 0.2mg/kg + 0.1mg/kg + 0.1mg/kg and IV paracetamol 10mg/mL for 3 days: loading dose 20mg/kg, following 7.5mg/kg q 6h (up to12 doses) |
| Indomethacin 25mg/mL and 0.45 sodium chloride | Placebo comparator | Drug: 0.45% Sodium Chloride, Drug: IndomethacinIntravenous (IV) indomethacin 25mg/mL q 24h for 3 days, dosages: 0.2mg/kg + 0.1mg/kg + 0.1mg/kg and NaCl 0.45% for 3 days, the same amount in mL as would have been given IV paracetamol |
Who may qualify
- Ages
- Up to 4 months
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (1 listed)
- Preterm infants (born before 37+0 gestation weeks) who are diagnosed to have a hemodynamically significant PDA and who, according to the decision of the attending clinician, need ibuprofen therapy, are eligible to this trial.
Key exclusion criteria (2 listed)
- severe malformation or suspected chromosomal defect
- other very severe life-threatening disease (e.g. very severe birth asphyxia or persistent pulmonary hypertension, etc.)
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 |
|---|---|---|
| Paracetamol 10Mg/mLAlso: Paracetamol Fresenius Kabi 10mg/mL infusion solutionExperimental drug | Drug | Indomethacin 25mg/mL and Paracetamol10mg/mL, Pedea 5mg/mL and Paracetamol 10mg/mL |
| 0.45% Sodium ChlorideAlso: NATRIUMKLORID BRAUN 4,5 mg/mL infusion solutionPlacebo comparator | Drug | Indomethacin 25mg/mL and 0.45 sodium chloride, Pedea 5mg/mL and 0.45 sodium chloride |
| IbuprofenAlso: Pedea 5mg/mL injection solutionStandard therapy | Drug | Pedea 5mg/mL and 0.45 sodium chloride, Pedea 5mg/mL and Paracetamol 10mg/mL |
| IndomethacinAlso: Liometacen 50mg/2mL injectionStandard therapy | Drug | Indomethacin 25mg/mL and 0.45 sodium chloride, Indomethacin 25mg/mL and Paracetamol10mg/mL |
Primary outcome
Ductal closure
Time frame: Neonatal internsive care unit (NICU) stay up to 12 weeks
Number of patients with ductal contraction without need for other PDA therapies
7 secondary outcomes
Need for ductal therapies
Time frame: NICU stay up to 12 weeks
Cardiac ultrasound findings
Time frame: NICU stay up to 12 weeks
Duration of any ventilation assist
Time frame: NICU stay up to 12 weeks
Paracetamol serum levels
Time frame: Study drug period up to 4 days
Paracetamol side effects
Time frame: Study drug period plus 7 days, up to 10 days
Long term complications of prematurity
Time frame: Hospital stay up to 18 weeks
Other long-term morbidity, and mortality
Time frame: Hospital stay up to 18 weeks
Results and safety
The study was stopped early (reason given: The PDA patients have vanished. The last recruitment took place in 2022. In the joint discussion of the principal researchers, it was concluded that PDA patients no longer have to be treated in Finland and the study was terminated.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Oct 2024.
- Background: PubMed 27215779Harkin P, Harma A, Aikio O, Valkama M, Leskinen M, Saarela T, Hallman M. Paracetamol Accelerates Closure of the Ductus Arteriosus after Premature Birth: A Randomized Trial. J Pediatr. 2016 Oct;177:72-77.e2. doi: 10.1016/j.jpeds.2016.04.066. Epub 2016 May 20.
- Background: PubMed 29105147Juujarvi S, Saarela T, Hallman M, Aikio O. Intravenous paracetamol was associated with closure of the ductus arteriosus in extremely premature infants. Acta Paediatr. 2018 Apr;107(4):605-610. doi: 10.1111/apa.14137. Epub 2017 Nov 17.
- Background: PubMed 26323200Harma A, Aikio O, Hallman M, Saarela T. Intravenous Paracetamol Decreases Requirements of Morphine in Very Preterm Infants. J Pediatr. 2016 Jan;168:36-40. doi: 10.1016/j.jpeds.2015.08.003. Epub 2015 Aug 29.
- Background: PubMed 24111688Aikio O, Harkin P, Saarela T, Hallman M. Early paracetamol treatment associated with lowered risk of persistent ductus arteriosus in very preterm infants. J Matern Fetal Neonatal Med. 2014 Aug;27(12):1252-6. doi: 10.3109/14767058.2013.854327. Epub 2013 Oct 31.
- Background: PubMed 30325529Juujarvi S, Kallankari H, Patsi P, Leskinen M, Saarela T, Hallman M, Aikio O. Follow-up study of the early, randomised paracetamol trial to preterm infants, found no adverse reactions at the two-years corrected age. Acta Paediatr. 2019 Mar;108(3):452-458. doi: 10.1111/apa.14614. Epub 2018 Nov 12.
- Thesis, Sanna Juujärvi, MBLink provided by the sponsor.
- Thesis, Pia Härkin, MDLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Outi Aikio, MD, PhD principal investigator
Oulu Univerisity Hospital
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Paracetamol 10Mg/mL, 0.45% Sodium Chloride and Ibuprofen in people with Patent Ductus Arteriosus, run by University of Oulu at 4 sites in Finland.
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 1 inclusion and 2 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: stopped early, as of the sponsor's last update on 18 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in Finland. 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. Some participants in this study may receive a placebo. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 was stopped early (reason given: The PDA patients have vanished. The last recruitment took place in 2022. In the joint discussion of the principal researchers, it was concluded that PDA patients no longer have to be treated in Finland and the study was terminated.). 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?
Ductal closure (time frame: Neonatal internsive care unit (NICU) stay up to 12 weeks). 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 NCT03648437, which also lists 5 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 18 Oct 2024.