Randomized trial of prolonged low-dose versus conventional-dose indomethacin for treating patent ductus arteriosus in very low birth weight infants.
OBJECTIVE
Indomethacin is used for closing the patent ductus arteriosus in premature infants. Prolonged low-dose indomethacin given over 6 days could potentially improve closure rates because ductal constriction is maintained long enough for more effective anatomic closure. We compared the efficacy of this regimen to conventional dosing in a cohort of very low birth weight infants.


METHODS
In a 2-arm clinical trial, 140 infants were randomized to either conventional dose (0.2 mg/kg/dose every 12 hours for 3 doses) or prolonged low-dose indomethacin (0.1 mg/kg/dose daily for 6 doses). The primary outcome measure was ductal closure rate, and the secondary outcomes were the need for a second course of treatment, surgical ligation rates, and side effects.


RESULTS
Ductal closure after 1 course of indomethacin was similar between the 2 groups: 68% for the conventional dose group and 72% for the prolonged low dose (mean difference -4%; 95% confidence interval: -19% to 11%). The incidence of transient oliguria was higher in the conventional dose group, 31% versus 9%. There was a trend toward more necrotizing enterocolitis in the prolonged low-dose group, 7.0% versus 1.4%.


CONCLUSIONS
There was no difference in efficacy between the 2 dosing regimens. In view of this and with its higher incidence of necrotizing enterocolitis, we do not recommend using prolonged low-dose indomethacin for closing the patent ductus arteriosus in very low birth weight infants.
Lee
Jiun
J
Department of Neonatology, KK Women's and Children's Hospital, Singapore, Singapore. ljiun@kkh.com.sg
Rajadurai
Victor Samuel
VS
Tan
Keng Wee
KW
Wong
Keng Yean
KY
Wong
Ee Hwee
EH
Leong
Joy Yoke Ngan
JY
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D004374:Ductus Arteriosus, Patent / Q000000981:diagnostic imaging / Q000188:drug therapy*; D015150:Echocardiography, Doppler; D020345:Enterocolitis, Necrotizing / Q000139:chemically induced; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage* / Q000009:adverse effects; D007231:Infant, Newborn; D007234:Infant, Premature; D007235:Infant, Premature, Diseases / Q000000981:diagnostic imaging / Q000188:drug therapy*; D019102:Infant, Very Low Birth Weight; D008297:Male
D000894:Anti-Inflammatory Agents, Non-Steroidal; D007213:Indomethacin