Co-administration of Acetaminophen With Ibuprofen to Improve Duct-Related Outcomes in Extremely Premature Infants

Patent ductus arteriosus (PDA), the most common cardiovascular complication of prematurity, is associated with higher mortality and morbidities in extremely low gestational age neonates (ELGANs, \< 27+0 weeks). Ibuprofen and acetaminophen, which act by reducing prostaglandin synthesis, are the most commonly used first and second line agents for PDA treatment across Canada. However, initial treatment failure with monotherapy is a major problem, occurring in \>60% ELGANs. Treatment failure is associated with worsening rates of mortality and bronchopulmonary dysplasia (BPD), while early treatment success can achieve rates comparable to neonates without PDA. Treatment failure resulting in prolonged disease exposure is thought to be a major contributor. Recently, combination therapy with acetaminophen and ibuprofen has emerged as a new treatment regime. Acetaminophen exerts anti-prostaglandin effect through a different receptor site than ibuprofen, providing a biological rationale for their synergistic action. The objective of this study is to evaluate the clinical impact, efficacy and safety of combination regime (Ibuprofen + IV Acetaminophen) for the first treatment course for PDA in ELGANs vs. Ibuprofen alone (current standard treatment). The study will also evaluate the effects of combination regime vs. ibuprofen alone on neurodevelopmental outcomes at 18-30 months corrected age.

NCT Number	NCT05340582
Lead Sponsor	Mount Sinai Hospital, Canada Collaborators: Sunnybrook Health Sciences Centre, McMaster Children's Hospital, The Rotunda Hospital, John Hunter Hospital, Royal Alexandra Hospital, Centre de Recheche du Centre Hospitalier Université Laval, Royal North Shore Hospital, Prince of Wales Hospital, Shatin, Hong Kong
Conditions	Patent Ductus Arteriosus After Premature Birth
Enrollment	310 participants
Start Date	2022-12-12
Primary Completion	2027-01 (estimated)
Study Completion	2027-04 (estimated)
Updated on ClinicalTrials.gov	2026-04-06