PAIR (Paracetamol and Ibuprofen Research) Pilot Trial

NCT ID: NCT04986839

Last Updated: 2023-10-30

Basic Information

• Recruitment Status: UNKNOWN
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 32 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-09-03
• Study Completion Date: 2024-01-01

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.

Conditions

Patent Ductus Arteriosus

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

Ibuprofen

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

Group Type: ACTIVE_COMPARATOR

Ibuprofen injection

Intervention Type: DRUG

Intravenous Ibuprofen

Paracetamol

To study the efficacy of Paracetamol (proposed new treatment) in treating hsPDA in comparison to Ibuprofen (current standard treatment) in preterm infants

Group Type: EXPERIMENTAL

Paracetamol injection

Intervention Type: DRUG

Intravenous Paracetamol

Interventions

Paracetamol injection

Intravenous Paracetamol

Intervention Type: DRUG

Ibuprofen injection

Intravenous Ibuprofen

Intervention Type: DRUG

Other Intervention Names

Acetaminophen; Brufen

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.

• Minimum Eligible Age: 23 Weeks
• Maximum Eligible Age: 32 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Manchester University NHS Foundation Trust

OTHER_GOV

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Arin Mukherjee, MRCPCH

Role: PRINCIPAL_INVESTIGATOR

Manchester University NHS Foundation Trust

Locations

Manchester University NHS Foundation Trust

Manchester, , United Kingdom

Site Status: RECRUITING

Countries

United Kingdom

Central Contacts

Karen Dockery

Role: CONTACT

karen.dockery@cmft.nhs.uk

0161 276 3863 ext. 63863

Facility Contacts

Karen Dockery

Role: primary

karen.dockery@cmft.nhs.uk

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

B01039

Identifier Type: -

Identifier Source: org_study_id