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.
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.
Aranda
Jacob V
JV
The Children's Hospital of Michigan, Wayne State University, Detroit, MI, USA. jaranda@downstate.edu
Clyman
Ronald
R
Cox
Blair
B
Van Overmeire
Bart
B
Wozniak
Paul
P
Sosenko
Ilene
I
Carlo
Waldemar A
WA
Ward
Robert M
RM
Shalwitz
Robert
R
Baggs
Geraldine
G
Seth
Anand
A
Darko
Laszlo
L
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
D008239:Lysine; C016106:solufenum; D007052:Ibuprofen