The efficiency and safety of low-dose intravenous indomethacin for closure of patent ductus arteriosus in preterm neonate: a randomized controlled trial

Patent ductus arteriosus (PDA) is a common complication in prematurity. Intravenous indomethacin, three doses, is an effective medication for closure PDA, but complications about renal impairment and gastrointestinal (GI) problems should be considered. This study aimed to compare the efficacy and safety of low-dose intravenous indomethacin (two doses) with the conventional three-dose for the closure of PDA in preterm neonates. A Randomized, Controlled, non-inferiority trial was performed from 1 May 2021 to February 2024. Preterm neonates <34 weeks or body weight <1,500 g with age <6 days with hemodynamically significant PDA were included. The patients were randomized into 2 groups: Group 1, 64 patients received 2 doses of indomethacin (0.2 mg/kg/dose), and Group 2, 64 patients received 3 doses of indomethacin. The baseline characteristics of both groups (gestational age (GA), gender, birth weight, respiratory disease, respiratory support, PDA size, left atrium/aorta ratio, and age of first indomethacin) show no statistically significant differences. The success rate for closure PDA in 72 h and 7 days has no statistically significant difference. The incidence of re-medication and surgical closure PDA, Necrotizing enterocolitis, GI bleeding, acute kidney injury, death, and hospital stay shows no statistically significant differences. Low-dose of Intravenous indomethacin was similar in efficiency and safety for closure of PDA in preterm newborns as the conventional dose, especially in preterm neonates with birth weight ≥ 1000 gm and GA > 28 weeks. This study was approved by the institutional review board of Chonburi hospital (040/2564) and was registered on Thai Clinical Trials Registry (TCTR20241122001) (22/11/2024).