Relative effectiveness and safety of pharmacotherapeutic agents for treatment of patent ductus arteriosus (PDA) in preterm infants: A National Comparative Effectiveness Research (CER) Project

Patent ductus arteriosus is a common heart condition that develops in preterm infants. Left untreated, some of them may progress to cause severe lung disease, kidney failure, bleeding in the brain, cerebral palsy and even death. The primary modality of treatment is medical, using drugs such as indomethacin and ibuprofen, failing which some preterm infants may need to undergo heart surgery. Wide variation exists in the choice of medication and dosage for treatment of PDA across Canadian neonatal intensive care units (NICUs). Standard doses of ibuprofen (10 mg per kg body weight followed by 2 doses of 5 mg per kg at 24 hour intervals) is the most commonly used treatment option. However, based on recent research, many centers have started to use higher doses of ibuprofen as the first choice of treatment. In this project we intend to conduct a comparative effectiveness study across Canadian NICUs to compare the effectiveness and safety of the common medical treatment options in preterm infants requiring PDA treatment. We will also try to understand the relevance of PDA treatment in the real world by comparing their outcomes to those who were not treated for PDA. In this study, each participating site will self-select and adhere to one of the pre-defined treatment protocols for all their preterm babies who will be treated for PDA. Data will be collected through the Canadian Neonatal Network (CNN) platform. Twenty NICUs across Canada have agreed to participate in this study. It is expected to take approximately 3 years to enroll the projected sample size of 1100 infants. We will establish the safety and effectiveness of commonly used PDA treatment options in a large contemporary patient cohort in Canada. In addition, we will examine key outcomes in relation to PDA treatment practices in the real world. This will inform future practice, reduce variability and generate data on the best treatment method to improve outcomes in preterm neonates with PDA.