Furosemide Safety in Preterm Infants at Risk for Bronchopulmonary Dysplasia: A Randomized Clinical Trial

Objective: To evaluate the safety of furosemide in preterm infants at the risk of developing bronchopulmonary dysplasia (BPD). Study design: This multicenter, randomized, dose-escalating, placebo-controlled trial enrolled infants born <29 weeks gestational age at 7-28 days postnatal age and at risk for BPD. Infants were randomized 3:1 (furosemide:placebo) into 2 cohorts with escalating doses of furosemide to a maximum of 1 mg/kg intravenous (IV; or 2 mg/kg enteral) every 24 hours (cohort 1; n = 40) or 1 mg/kg IV (or 2 mg/kg enteral) every 6 hours (cohort 2; n = 40) for 28 days. Effects of furosemide on total adverse events (AEs; primary outcome), BPD, death, hearing loss, serum electrolyte AEs, and nephrocalcinosis were estimated using logistic regression adjusted for gestational age. Results: We found 293 AEs in 74 of 80 (93%) infants, including 223 AEs among 56 of 61 (92%) infants who received furosemide and 70 AEs among 18 of 19 (95%) infants who received placebo (P > .99). Adjusted analysis among all groups showed no difference in the odds of having moderate-to-severe BPD or death at 36 weeks post-menstrual age (P = .32), hearing loss (P = .78), or nephrocalcinosis (P = .39). For serum electrolyte AE, OR (furosemide vs placebo) was 4.46 (95% CI, 1.06-21.70; P = .048) for cohort 1 and 7.89 (95% CI, 1.50-61.91; P = .023) for cohort 2. Conclusions: In preterm infants, furosemide did not increase the overall incidence of AEs, hearing loss, or nephrocalcinosis, but did increase the incidence of electrolyte abnormalities. Furosemide given for 28 consecutive days was not associated with a difference in moderate-to-severe BPD or death at 36 weeks postmenstrual age. Clinicaltrials.gov: NCT02527798.