Patent Ductus ArteriosusPhase 2/3PAIRNCT04986839
PAIR (Paracetamol and Ibuprofen Research) Pilot Trial
A Phase 2/3 study testing Paracetamol injection and Ibuprofen injection in people with Patent Ductus Arteriosus, run by Manchester University NHS Foundation Trust at 1 site in United Kingdom.
Trial summary
Presence of Patent Ductus Arteriosus is detrimental to an infant born prematurely. The primary objective is to study the efficacy of Paracetamol (proposed new treatment) in treating haemodynamic significant Patent Ductus Arteriosus (hsPDA) in comparison to Ibuprofen (current standard treatment) in preterm infants. Read more about this study
- Who is it for?
- Ages 23 to 32 weeks
- Conditions the study is for
- Patent Ductus Arteriosus
- What is being tested?
- Paracetamol injection and Ibuprofen injection
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 3 Sep 2021to 1 Jan 2024
- 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 23 to 32 weeks
- All sexes
- No healthy volunteers
- Child
Who may be able to join
- Gestational age - <32 weeks OR birth weight < 1500 grams
- Postnatal age ≤ 28 days
- Meets criteria for hsPDA
- Clinician's decision to treat PDA
Who cannot join
- Contraindication for administration of Ibuprofen (cyclooxygenase-inhibitors) or Paracetamol, such as: active bleeding (e.g. intracranial or gastrointestinal haemorrhage), thrombocytopenia (<50x109/L), renal failure (raised creatinine (>100 micromole/l) or oliguria (<0.5 mL/kg/hour), known or suspected necrotising enterocolitis, any gastric or intestinal perforation, pre-treatment abnormal liver function tests (ALT > upper normal limit of the reference range, Bilirubin > National Institute of Clinical Excellence exchange phototherapy level).
- Previous use of Ibuprofen or Paracetamol prior to randomisation.
- Persistent pulmonary hypertension (ductal right-to-left shunt ≧33% of cardiac cycle).
- Congenital heart defect, other than PDA or Patent Foramen Ovale (PFO).
- Life-threatening congenital birth defects.
- Chromosomal abnormalities and/or congenital anomalies associated with abnormal neurodevelopment.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site, 1 recruiting
- Recruiting
Manchester University NHS Foundation Trust
Manchester, M13 9WL
Karen Dockery, karen.dockery@cmft.nhs.uk
About this study
Official title: PAIR (Paracetamol and Ibuprofen Research) Study: A Randomised Controlled Trial Comparing IV Paracetamol With IV Ibuprofen in the Management of Haemodynamically Significant Patent Ductus Arteriosus
Presence of Patent Ductus Arteriosus is detrimental to an infant born prematurely. The primary objective is to study the efficacy of Paracetamol (proposed new treatment) in treating haemodynamic significant Patent Ductus Arteriosus (hsPDA) in comparison to Ibuprofen (current standard treatment) in preterm infants. Outcome of such treatment will check on the conversion of hsPDA to non-hsPDA. All preterm infants (born at <32 weeks gestational age or birth weight < 1500 grams) with haemodynamically significant patent ductus arteriosus (hsPDA) who are ≤ 28 days old will be included over 2 years. Sample size 32. Secondary outcomes of this study will compare
- BPD (broncho-pulmonary dysplasia) free survival at 36 weeks post menstrual age (PMA), 2) incidence of complications of prematurity in each group and 3) to record any evidence of adverse effects with Paracetamol or Ibuprofen.
Read the detailed description
Patent Ductus Arteriosus (PDA) is present in 40-60 percent of preterm infants. A persistent PDA with a large left to right ductal shunt may be 'haemodynamically significant' (hsPDA) resulting in pulmonary hyper-perfusion and systemic hypo-perfusion. The association of a PDA with an increased incidence of pulmonary haemorrhage, bronchopulmonary dysplasia and prolonged need for ventilatory support is ascribed to pulmonary hyper-perfusion, whereas necrotising enterocolitis, renal failure, cerebral haemorrhage, and periventricular leukomalacia are consequences of systemic hypo-perfusion. In the United Kingdom, Ibuprofen (a non-steroidal anti-inflammatory drug, NSAID) is used to treat hsPDA in preterm babies. Paracetamol has come up recently as a promising alternative with fewer side effects and has been used in the management of PDA with promising results. However, the current available body of evidence is considered to be of moderate to low quality and hence its effectiveness and safety profile is not fully established in this patient population. The primary objective is to study the efficacy of IV paracetamol in treating hsPDA in comparison to IV ibuprofen in preterm infants born at less than 32 weeks' gestation OR less than 1500 grams birth weight.
- Conditions
- Patent Ductus Arteriosus
- Being tested
- Paracetamol injection, Ibuprofen injection
- 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.
Paracetamol injectionDrug
Also called Acetaminophen
Intravenous Paracetamol
Ibuprofen injectionDrug
Also called Brufen
Intravenous Ibuprofen
| Study group | Role | What they receive |
|---|---|---|
| Ibuprofen | Active comparator | Standard treatment arm which will provide the comparator arm to the proposed new treatment. This is routine standard of practice Receives: Drug: Ibuprofen injection |
| Paracetamol | Experimental | To study the efficacy of Paracetamol (proposed new treatment) in treating hsPDA in comparison to Ibuprofen (current standard treatment) in preterm infants Receives: Drug: Paracetamol injection |
What is being measured
The primary outcome is the main question the study is designed to answer.
Conversion of haemodynamically significant PDA (hsPDA) to non-hsPDA
Efficacy of Paracetamol (proposed new treatment) in treating hsPDA in comparison to Ibuprofen (current standard treatment) in preterm infants. The diagnosis of hsPDA will be made in the presence of supportive clinical signs and at least three of the following echocardiogram indices:
- PDA diameter ≥2.0 mm in 2D ii) Ductal flow pattern ('growing' pattern or pulsatile with Vmax/Vmin ≥ 2) iii) Retrograde post ductal aortic/coeliac/SMA (superior mesenteric artery) diastolic flow iv) LA/Ao ratio (left atrium:Aorta) ≥ 2 v) LVO (Left ventricular output) ≥ 300 ml/kg/min vi) Mitral valve E/A ratio ≥ 1
An echocardiogram will be carried out within 72 hours of the last dose and PDA will be classified as non-hsPDA based on the following criteria - PDA closed OR any two of the following three parameters i) Reduction of PDA diameter >50% (2D) ii) Restrictive or closing Ductal flow pattern iii) LA: Ao ratio < 1.5
Measured: 3 days
Secondary outcomes (3)
Broncho-pulmonary dysplasia (BPD) free survival at 36 weeks post menstrual age (PMA)
BPD free survival at 36 weeks PMA
Measured: Age up to 36 weeks PMA
Incidence of complications of prematurity in each group
- Necrotising enterocolitis (NEC, Bell stage ≥IIa)
- Significant intraventricular haemorrhage ( IVH) grade 3/4)
- Retinopathy of Prematurity (ROP) requiring treatment
Measured: Age up to 36 weeks PMA
To record any evidence of adverse effects with Paracetamol or Ibuprofen
. a) Renal impairment (elevated urea and creatinine > upper limit of normal range) b) Hepatic impairment (elevated liver enzymes ALT or Aspartate transaminase (AST) > upper limit of normal) c) Significant gastrointestinal or non-gastrointestinal bleeding requiring intervention
Measured: Within 7 days of starting the trial medications
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Aug 2021
- Study start3 Sep 2021
- Primary completion1 Dec 2023 (estimated)
- Study completion1 Jan 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)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 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- The study involves two-arm parallel assignment where one group receives standard treatment (Ibuprofen) and the other group receives investigational medicinal product (Paracetamol) to treat Patent Ductus Arteriosus
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 32 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Manchester University NHS Foundation Trust
- Sponsor type
- Other government
- Responsible party
- Sponsor
- Investigators
- Arin Mukherjee, MRCPCH, Principal investigator, Manchester University NHS Foundation Trust
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04986839
- Sponsor's protocol ID
- B01039
- Acronym
- PAIR
- Status last verified
- Oct 2023
- First submitted
- 19 Jul 2021
- Last updated
- 30 Oct 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mukherjee A, Gupta A, Fullwood C, Gottstein R. Paracetamol or ibuprofen? A pilot study comparing rescue therapy for PDA in preterm infants within the first month. Front Pediatr. 2026 Jan 2;13:1717284. doi: 10.3389/fped.2025.1717284. eCollection 2025.
PubMed 41550606
Study at a glance
From the registry record, last updated by the sponsor on 30 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- PAIR (Paracetamol and Ibuprofen Research) Study: A Randomised Controlled Trial Comparing IV Paracetamol With IV Ibuprofen in the Management of Haemodynamically Significant Patent Ductus Arteriosus
- ClinicalTrials.gov ID
- NCT04986839
- Acronym / sponsor ID
- PAIR / B01039
- Conditions
- Patent Ductus Arteriosus
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 32 participants (estimated)
- Lead sponsor
- Manchester University NHS Foundation TrustOther government
- Study start
- 3 Sep 2021 (actual)
- Primary completion
- 1 Dec 2023 (estimated)
- Study completion
- 1 Jan 2024 (estimated)
- First posted
- 3 Aug 2021 (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.
Presence of Patent Ductus Arteriosus is detrimental to an infant born prematurely. The primary objective is to study the efficacy of Paracetamol (proposed new treatment) in treating haemodynamic significant Patent Ductus Arteriosus (hsPDA) in comparison to Ibuprofen (current standard treatment) in preterm infants. Outcome of such treatment will check on the conversion of hsPDA to non-hsPDA. All preterm infants (born at <32 weeks gestational age or birth weight < 1500 grams) with haemodynamically significant patent ductus arteriosus (hsPDA) who are ≤ 28 days old will be included over 2 years. Sample size 32. Secondary outcomes of this study will compare
- BPD (broncho-pulmonary dysplasia) free survival at 36 weeks post menstrual age (PMA), 2) incidence of complications of prematurity in each group and 3) to record any evidence of adverse effects with Paracetamol or Ibuprofen.
Detailed description
Patent Ductus Arteriosus (PDA) is present in 40-60 percent of preterm infants. A persistent PDA with a large left to right ductal shunt may be 'haemodynamically significant' (hsPDA) resulting in pulmonary hyper-perfusion and systemic hypo-perfusion. The association of a PDA with an increased incidence of pulmonary haemorrhage, bronchopulmonary dysplasia and prolonged need for ventilatory support is ascribed to pulmonary hyper-perfusion, whereas necrotising enterocolitis, renal failure, cerebral haemorrhage, and periventricular leukomalacia are consequences of systemic hypo-perfusion. In the United Kingdom, Ibuprofen (a non-steroidal anti-inflammatory drug, NSAID) is used to treat hsPDA in preterm babies. Paracetamol has come up recently as a promising alternative with fewer side effects and has been used in the management of PDA with promising results. However, the current available body of evidence is considered to be of moderate to low quality and hence its effectiveness and safety profile is not fully established in this patient population. The primary objective is to study the efficacy of IV paracetamol in treating hsPDA in comparison to IV ibuprofen in preterm infants born at less than 32 weeks' gestation OR less than 1500 grams birth weight.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
- Model description
- The study involves two-arm parallel assignment where one group receives standard treatment (Ibuprofen) and the other group receives investigational medicinal product (Paracetamol) to treat Patent Ductus Arteriosus
| Arm | Type | Receives |
|---|---|---|
| Ibuprofen | Active comparator | Drug: Ibuprofen injectionStandard treatment arm which will provide the comparator arm to the proposed new treatment. This is routine standard of practice |
| Paracetamol | Experimental | Drug: Paracetamol injectionTo study the efficacy of Paracetamol (proposed new treatment) in treating hsPDA in comparison to Ibuprofen (current standard treatment) in preterm infants |
Who may qualify
- Ages
- 23 to 32 weeks
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- Gestational age - <32 weeks OR birth weight < 1500 grams
- Postnatal age ≤ 28 days
- Meets criteria for hsPDA
- Clinician's decision to treat PDA
Key exclusion criteria (6 listed)
- Contraindication for administration of Ibuprofen (cyclooxygenase-inhibitors) or Paracetamol, such as: active bleeding (e.g. intracranial or gastrointestinal haemorrhage), thrombocytopenia (<50x109/L), renal failure (raised creatinine (>100 micromole/l) or oliguria (<0.5 mL/kg/hour), known or suspected necrotising enterocolitis, any gastric or intestinal perforation, pre-treatment abnormal liver function tests (ALT > upper normal limit of the reference range, Bilirubin > National Institute of Clinical Excellence exchange phototherapy level).
- Previous use of Ibuprofen or Paracetamol prior to randomisation.
- Persistent pulmonary hypertension (ductal right-to-left shunt ≧33% of cardiac cycle).
- Congenital heart defect, other than PDA or Patent Foramen Ovale (PFO).
- Life-threatening congenital birth defects.
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 injectionAlso: AcetaminophenIntravenous Paracetamol | Drug | Paracetamol |
| Ibuprofen injectionAlso: BrufenIntravenous Ibuprofen | Drug | Ibuprofen |
Primary outcome
Conversion of haemodynamically significant PDA (hsPDA) to non-hsPDA
Time frame: 3 days
Efficacy of Paracetamol (proposed new treatment) in treating hsPDA in comparison to Ibuprofen (current standard treatment) in preterm infants. The diagnosis of hsPDA will be made in the presence of supportive clinical signs and at least three of the following echocardiogram indices: i) PDA diameter ≥2.0 mm in 2D ii) Ductal flow pattern ('growing' pattern or pulsatile with Vmax/Vmin ≥ 2) iii) Retrograde post ductal aortic/coeliac/SMA (superior mesenteric artery) diastolic flow iv) LA/Ao ratio (left atrium:Aorta) ≥ 2 v) LVO (Left ventricular output) ≥ 300 ml/kg/min vi) Mitral valve E/A ratio ≥ 1 An echocardiogram will be carried out within 72 hours of the last dose and PDA will be classified as non-hsPDA based on the following criteria - PDA closed OR any two of the following three parameters i) Reduction of PDA diameter >50% (2D) ii) Restrictive or closing Ductal flow pattern iii) LA: Ao ratio < 1.5
3 secondary outcomes
Broncho-pulmonary dysplasia (BPD) free survival at 36 weeks post menstrual age (PMA)
Time frame: Age up to 36 weeks PMA
Incidence of complications of prematurity in each group
Time frame: Age up to 36 weeks PMA
To record any evidence of adverse effects with Paracetamol or Ibuprofen
Time frame: Within 7 days of starting the trial medications
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Oct 2023.
- Derived from this study: PubMed 41550606Mukherjee A, Gupta A, Fullwood C, Gottstein R. Paracetamol or ibuprofen? A pilot study comparing rescue therapy for PDA in preterm infants within the first month. Front Pediatr. 2026 Jan 2;13:1717284. doi: 10.3389/fped.2025.1717284. eCollection 2025.
- 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.
Arin Mukherjee, MRCPCH principal investigator
Manchester University NHS Foundation Trust
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 Paracetamol injection and Ibuprofen injection in people with Patent Ductus Arteriosus, run by Manchester University NHS Foundation Trust at 1 site in United Kingdom.
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 6 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: status not confirmed, as of the sponsor's last update on 30 Oct 2023. 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 United Kingdom. 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?
Contact Karen Dockery (0161 276 3863 ext. 63863, karen.dockery@cmft.nhs.uk), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Conversion of haemodynamically significant PDA (hsPDA) to non-hsPDA (time frame: 3 days). 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 NCT04986839, which also lists 1 linked publication.
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 30 Oct 2023.