PAIR (Paracetamol and Ibuprofen Research) Pilot Trial

NCT04986839 | Unknown Phase 2 DMC

• 1 other identifier: B01039
• Study Type: interventional
• Target: 32
• Locations: 1 country
• Sites: 1

Brief 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. 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 1\) 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.

Conditions

Patent Ductus Arteriosus

Outcome Measures

Primary Outcomes (1)

• 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: 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 days

Secondary Outcomes (3)

• Broncho-pulmonary dysplasia (BPD) free survival at 36 weeks post menstrual age (PMA)

  Age up to 36 weeks PMA

• Incidence of complications of prematurity in each group

  Age up to 36 weeks PMA

• To record any evidence of adverse effects with Paracetamol or Ibuprofen

  Within 7 days of starting the trial medications

Study Arms (2)

Ibuprofen

ACTIVE COMPARATOR

Standard treatment arm which will provide the comparator arm to the proposed new treatment. This is routine standard of practice

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

Drug: Paracetamol injection

Interventions

Paracetamol injection DRUG

Intravenous Paracetamol

Also known as: Acetaminophen

Paracetamol

Ibuprofen injection DRUG

Intravenous Ibuprofen

Also known as: Brufen

Ibuprofen

Eligibility Criteria

• Age: 23 Weeks - 32 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Gestational age - \<32 weeks OR birth weight \< 1500 grams
• Postnatal age ≤ 28 days
• Meets criteria for hsPDA
• Clinician's decision to treat PDA

You may not qualify if:

• 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.

Sponsors & Collaborators

• Manchester University NHS Foundation Trust: lead

Study Sites (1)

Manchester University NHS Foundation Trust

Manchester, M13 9WL, United Kingdom

RECRUITING

Related Publications (1)

• 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.

  PMID: 41550606 DERIVED

MeSH Terms

Conditions

Ductus Arteriosus, Patent

Interventions

Acetaminophen; Ibuprofen

Condition Hierarchy (Ancestors)

Heart Defects, Congenital; Cardiovascular Abnormalities; Cardiovascular Diseases; Heart Diseases; Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Acetanilides; Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Phenylpropionates; Acids, Carbocyclic; Carboxylic Acids

Study Officials

• Arin Mukherjee, MRCPCH

  Manchester University NHS Foundation Trust

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Karen Dockery

CONTACT

0161 276 3863; karen.dockery@cmft.nhs.uk

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Infants will be randomized. Outcome assessor of the treatment will be blinded to the trial participants. No allocation concealment is done.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR

Model Details: 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

Study Record Dates

• First Submitted: July 19, 2021
• First Posted: August 3, 2021
• Study Start: September 3, 2021
• Primary Completion: December 1, 2023
• Study Completion: January 1, 2024
• Last Updated: October 30, 2023

Record last verified: 2023-10

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)