Global Trace Module in Safety of Furosemide in Premature Infants at Risk of Bronchopulmonary Dysplasia

Global Trace Module (Specimen Information)
Study Description
The primary objective of this multi-center, randomized, dose-escalating, placebo-controlled study was to describe the safety of furosemide in premature infants at risk of bronchopulmonary dysplasia (BPD). The secondary objectives were to evaluate the preliminary effectiveness and pharmacokinetics of furosemide. The rates of adverse events (AEs), serious adverse events (SAEs) and related SAEs were similar by cohort among furosemide treated participants. Among most safety events of special interest (death, failed hearing test, nephrocalcinosis/nephrolithiasis), there were no significant differences seen between furosemide versus placebo treated participants. The lack of difference between furosemide and placebo group for failed hearing test and nephrocalcinosis/nephrolithiasis is consistent with recent manuscripts comparing infants exposed to furosemide versus unexposed and with systematic reviews of the safety of furosemide. However, there were more electrolyte abnormality AEs in the furosemide versus placebo infants. There was no difference in the preliminary effectiveness outcomes of moderate to severe BPD or death or in the change of BPD over time. In the population pharmacokinetics analysis of furosemide in premature neonates and infants, body weight and postnatal age were found to be influential covariates on furosemide clearance. In premature infants at risk for BPD, furosemide increased the risk of electrolyte AEs but did not increase overall risk of AEs, hearing loss, or nephrocalcinosis/nephrolithiasis. The safety population included 80 premature infant participants who were randomized and dosed to either placebo or furosemide.