Grant: Project Grant

In Canada, about 900 babies each year are born very early (<26 weeks of gestation) and have a high chance of dying or having a serious bleed in the brain. Families of these extremely preterm babies consider preventing severe brain bleeding as critical to their child's health and well-being. A medicine called indomethacin, when given intravenously in 3-doses shortly after birth, is known to reduce severe brain bleeding. But use of this drug is variable among clinicians working in the neonatal intensive care unit (NICU) due to its side effects on the gut and possible harm when used with other medications. Emerging evidence suggests that a single low-dose indomethacin regimen may be equally effective in reducing severe brain bleeding as compared to a traditional 3-dose regimen. No previous clinical trial has specifically explored the use of single dose indomethacin in babies born <26 weeks of gestation. Therefore, a pilot trial to assess if extremely preterm babies can be enrolled in such a trial within a short time frame after birth is needed before designing a large multi-center trial. We propose a blinded randomized controlled trial, a study design where babies born <26 weeks will be randomly assigned within 12 hours of birth to either a single dose of intravenous indomethacin or similar looking placebo in the form a saline solution. In this study the care providers and researchers will be unaware as to which baby receives indomethacin and which baby receives placebo to ensure no one's expectations or biases can influence the results. We will conduct the study in multiple NICUs across Canada, the United States and Australia and will enroll 104 babies born <26 weeks or <750 g birth weight over a period of 12 months. This study will help us determine if we can conduct a large definitive trial on use of single dose of indomethacin in the smallest babies born <26 weeks of gestation to reduce severe brain bleeding.