A randomized controlled trial on the use of oral ibuprofen to close patent ductus arteriosus in premature infants

Article type: Research Article

Authors: Salama, Husam | Alsisi, Amal | Al-Rifai, Hilal | Shaddad, Afaf | Samawal, Lutfi | Habboub, Lina | Masoud, Ahmed

Affiliations: Neonatal Intensive Care, Department of Pediatrics, Women's hospital, Hamad Medical Center, Doha, Qatar

Note: [] Corresponding author: Dr. Hilal Al-Rifai, Neonatal Intensive Care, Department of Pediatrics, Women's Hospital, Hamad Medical Center, Doha, Qatar. Tel.: +974 439 3513; Fax: +974 439 3298; E-mail: [email protected]

Abstract: Objective: To compare the efficacy of oral ibuprofen with that of intravenous indomethacin for closure of significant patent ductus arteriosus (PDA) in premature infants. Study design: We conducted a prospective randomized controlled trial on premature infants (gestational age < 34 weeks and birth weight < 2500 grams) diagnosed with hemodynamically significant PDA. After parental consent, infants were randomly assigned to one of two groups: group A, infants received intravenous indomethacin, and group B infants received oral ibuprofen. Echocardiography was performed before enrollment and after each course of treatment. The study was designed with a one-way cross over. Infants diagnosed with significant PDA after receiving two courses of ibuprofen were then offered a course of intravenous indomethacin. Results: A total of 41 infants were recruited in the study; of them 20 infants received indomethacin and 21 infants received oral ibuprofen. The mean gestational age was 27 weeks ± 1.5, the mean birth weight was 1050 grams ± 900 grams, and the mean age at the start of therapy was 7 days ± 1.8. Complete closure of the PDA was achieved with indomethacin in 10 infants, and with ibuprofen in 14 infants (p = 0.3). Surgical ligations were performed on four infants in the indomethacin group and two infants in the ibuprofen group. Three infants in the ibuprofen group were re-assigned to the group receiving indomethacin. Overall gastrointestinal complications in the indomethacin and ibuprofen groups were not different (9 vs. 5 infants, respectively; > 0.2). Bowel perforation occurred in 4 infants in the indomethacin group and 1 infant in the ibuprofen group, while benign feeding intolerance developed in 3 and 4 infants respectively. No infants developed thrombocytopenia and there were no significant renal function changes in either group. However, there were five mortalities in the indomethacin group and three in the ibuprofen group. Conclusion: This study suggests that oral ibuprofen could be a valid alternative to indomethacin for the treatment of PDA in premature infants < 34 weeks. Although ibuprofen was associated with less side effects, larger cohort studies are needed to address safety of the use of oral ibuprofen in premature infants before any recommendation.

Keywords: PDA, preterm, oral ibuprofen, NICU, indomethacin

Journal: Journal of Neonatal-Perinatal Medicine, vol. 1, no. 3, pp. 153-158, 2008