Clinical trial NCT04986839: PAIR (Paracetamol and Ibuprofen Research) Pilot Trial
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Patent Ductus Arteriosus
Lead sponsor: Manchester University NHS Foundation Trust
Sponsor class: OTHER_GOV
First posted: 2021-08-03
Enrollment: 32
Sex: ALL
Minimum age (years): 23
Maximum age (years): 32
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention 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
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

* 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.

Primary outcomes:
measure: Conversion of haemodynamically significant PDA (hsPDA) to non-hsPDA
timeFrame: 3 days
Secondary outcomes:
measure: Broncho-pulmonary dysplasia (BPD) free survival at 36 weeks post menstrual age (PMA)
timeFrame: Age up to 36 weeks PMA
measure: Incidence of complications of prematurity in each group
timeFrame: Age up to 36 weeks PMA
measure: To record any evidence of adverse effects with Paracetamol or Ibuprofen
timeFrame: Within 7 days of starting the trial medications
Other outcomes:
Locations:
city: Manchester
country: United Kingdom
facility: Manchester University NHS Foundation Trust
Study officials:
affiliation: Manchester University NHS Foundation Trust
name: Arin Mukherjee, MRCPCH
role: PRINCIPAL_INVESTIGATOR
References: