Furosemide Safety in Preterm Infants at Risk for Bronchopulmonary Dysplasia: A Randomized Clinical Trial
05/2025
Journal Article
Authors:
Greenberg, R. G.;
Lang, J.;
Smith, P. B.;
Shekhawat, P.;
Courtney, S. E.;
Hudak, M. L.;
Moya, F.;
Iyengar, A.;
Eldemerdash, A.;
Bloom, B.;
Go, M.;
Hanna, M.;
Rhein, L.;
Aliaga, S.;
Lewis, T.;
Febre, A.;
Kiefer, A. S.;
Bhatt-Mehta, V.;
Khoury, J. A.;
Selewski, D.;
Anand, R.;
Martz, K.;
Payne, E. H.;
Zimmerman, K. O.;
Benjamin, D. K., Jr.;
Laughon, M.;
Best Pharmaceuticals for Children Act - Pediatric Trials Network Steering, Committee
Journal:
J Pediatr
PMID:
40306549
URL:
https://www.ncbi.nlm.nih.gov/pubmed/40306549
DOI:
10.1016/j.jpeds.2025.114629
Keywords:
Bronchopulmonary dysplasia Electrolytes Furosemide Preterm infants Safety
Abstract:
OBJECTIVE: To evaluate the safety of furosemide in preterm infants at risk of developing bronchopulmonary dysplasia (BPD).; Study design This multi-center, 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. The primary outcome effect of furosemide on total adverse events (AEs) and secondary outcomes BPD, death, hearing loss, serum electrolyte AEs, and nephrocalcinosis were estimated using logistic regression adjusted for gestational age. RESULTS: We found 293 AEs in 74/80 (93%) infants, including 223 AEs among 56/61 (92%) infants who received furosemide and 70 AEs among 18/19 (95%) infants who received placebo (P>0.99). 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=0.32), hearing loss (P=0.78), or nephrocalcinosis (P=0.39). For serum electrolyte AE, odds ratio (furosemide vs placebo) was 4.46 (95% CI, 1.06-21.70; P=0.048) for cohort 1 and 7.89 (95% CI, 1.50-61.91; P=0.023) for cohort 2. CONCLUSIONS: In preterm infants, furosemide did not increase 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 post-menstrual age. CLINICALTRIALS: GOV: NCT02527798.
