title: A randomized, double-blind, placebo-controlled trial on intravenous ibuprofen L-lysine for the early closure of nonsymptomatic patent ductus arteriosus within 72 hours of birth in extremely low-birth-weight infants.
abstract: A multicenter, double-blind, randomized, placebo-controlled trial was conducted to evaluate the efficacy and safety of intravenous (IV) ibuprofen (L-lysine) for the early closure of nonsymptomatic patent ductus arteriosus (PDA) within 72 hours of birth in extremely low-birth-weight (ELBW) infants with evidence of ductal shunting by echocardiogram. Eleven sites enrolled 136 infants with nonsymptomatic early PDA (gestational age < 30 weeks; body weight 500 to 1000 g) to receive a 3-day course (10 mg/kg, 5 mg/kg, and 5 mg/kg) of IV ibuprofen ( N = 68) or placebo ( N = 68). Cardiac echocardiogram was performed on study days 1 and 14, and with rescue. Infants were followed to 36 weeks postconceptional age. Patient demographics, mean (standard deviation), were similar between ibuprofen and placebo: birth weight: 798.5 g (128.7) versus 797.3 g (132.8); gestational age: 26.1 weeks (1.3) versus 26.2 weeks (1.4); and age at first dose: 1.5 days (0.7). The intent-to-treat analysis of the primary endpoint, subjects rescued, died, or dropped through study day 14, was 21/68 (30.9%) with ibuprofen and 36/68 (52.9%) for placebo ( P = 0.005). Death, intraventricular hemorrhage, necrotizing enterocolitis, daily fluid intake/output, liver function, bronchopulmonary dysplasia, and retinopathy of prematurity did not differ. A trend toward decreased periventricular leukomalacia by ibuprofen was noted. IV ibuprofen was effective and safe in the early closure of PDA in preterm neonates.
authors.affiliation: The Children's Hospital of Michigan, Wayne State University, Detroit, MI, USA. jaranda@downstate.edu
authors.forename: Jacob V
authors.initials: JV
authors.lastname: Aranda
authors.forename: Ronald
authors.initials: R
authors.lastname: Clyman
authors.forename: Blair
authors.initials: B
authors.lastname: Cox
authors.forename: Bart
authors.initials: B
authors.lastname: Van Overmeire
authors.forename: Paul
authors.initials: P
authors.lastname: Wozniak
authors.forename: Ilene
authors.initials: I
authors.lastname: Sosenko
authors.forename: Waldemar A
authors.initials: WA
authors.lastname: Carlo
authors.forename: Robert M
authors.initials: RM
authors.lastname: Ward
authors.forename: Robert
authors.initials: R
authors.lastname: Shalwitz
authors.forename: Geraldine
authors.initials: G
authors.lastname: Baggs
authors.forename: Anand
authors.initials: A
authors.lastname: Seth
authors.forename: Laszlo
authors.initials: L
authors.lastname: Darko
mesh_terms: D004311:Double-Blind Method; D004374:Ductus Arteriosus, Patent / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D005260:Female; D006801:Humans; D007052:Ibuprofen / Q000008:administration & dosage / Q000031:analogs & derivatives*; D052577:Infant, Extremely Low Birth Weight; D007231:Infant, Newborn; D007275:Injections, Intravenous; D008239:Lysine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D008297:Male; D013997:Time Factors; D016896:Treatment Outcome; D014463:Ultrasonography
chemical_list: D008239:Lysine; C016106:solufenum; D007052:Ibuprofen