March 27, 2018
2 min read

Oral ibuprofen boosts patent ductus arteriosus closure in preterm infants

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Infants treated with a high dose of oral ibuprofen were more likely to have a hemodynamically significant patent ductus arteriosus closure compared with those treated with standard doses of IV indomethacin or IV ibuprofen, according to a systematic review and analysis published in JAMA.

Souvik Mitra, MD, assistant professor in the department of pediatrics at Dalhousie University in Nova Scotia, Canada, and colleagues analyzed data from 4,802 preterm infants with patent ductus arteriosus from 68 randomized trials. The trials analyzed the effects of an oral or IV formulation of ibuprofen, indomethacin or acetaminophen compared with placebo, another medication or no treatment on hemodynamically significant patent ductus arteriosus. Studies with prophylactic medication use or surgery as a primary treatment modality were excluded.

The primary outcome was hemodynamically significant patent ductus arteriosus closure up to 1 week after the first dose of the treatment. Closure was diagnosed clinically or by echocardiography. Secondary outcomes included mortality, surgical closure, intraventricular hemorrhage and necrotizing enterocolitis.

In all studies, treatment modalities included 14 different variations of ibuprofen, indomethacin or acetaminophen. Patent ductus arteriosus closure occurred in 67.4% of infants.

Infants treated with a high dose of oral ibuprofen were more likely to have patent ductus arteriosus closure compared with a standard dose of IV indomethacin (OR = 2.35; 95% credible interval [CrI], 1.08-5.31; absolute risk difference = 124 more per 1,000 infants; 95% CrI, 14-188) and a standard dose of IV ibuprofen (OR = 3.59; 95% CrI, 1.64-8.17; absolute risk difference = 199 more per 1,000 infants; 95% CrI, 95-258).

A high dose of oral ibuprofen was the best treatment option for patent ductus arteriosus closure (mean surface under the cumulative ranking [SUCRA] = 0.89; standard deviation = 0.12) and to reduce surgical patent ductus arteriosus ligation (mean SUCRA = 0.98; standard deviation = 0.08). Results were similar in sensitivity and meta-regression analyses.

Necrotizing enterocolitis, mortality or intraventricular hemorrhage did not significantly differ in infants treated with placebo or no treatment vs. other treatment modalities.

“The overall high-ranking probabilities across outcomes suggest that high and standard doses of oral ibuprofen and oral acetaminophen could be effective alternatives to the standard regimens of intravenous ibuprofen and intravenous indomethacin currently used to close a hemodynamically significant [patent ductus arteriosus],” Mitra and colleagues wrote. “Well-designed randomized clinical trials with optimal sample sizes to detect clinically important differences in effectiveness and safety using such medications are needed to confirm or refute the validity of the network meta-analysis results.” – by Darlene Dobkowski

Disclosures: The authors report no relevant financial disclosures.