Canada: Indomethacin may be effective in closing a symptomatic PDA in preterm infants as compared to placebo or no treatment, according to a recent Cochrane review. However, according to the authors, evidence is insufficient regarding indomethacin effects on medication-related adverse effects and clinically relevant outcomes.
Symptomatic patent ductus arteriosus (PDA) increases risk of morbidity and mortality in preterm infants. The use of indomethacin, a non-selective cyclooxygenase inhibitor, has shown short-term clinical benefits in these infants. However, the effect of indomethacin in preterm infants with a symptomatic PDA is still not explored. Souvik Mitra, Dalhousie University & IWK Health Centre, Halifax, Canada, and colleagues aimed to determine the safety and efficacy of indomethacin versus placebo or no treatment in reducing mortality and morbidity in preterm infants with a symptomatic PDA.
For the purpose, the researchers used the standard search strategy of Cochrane Neonatal to search for Cochrane Central Register of Controlled Trials on 31 July 2020. Clinical trials databases and reference lists of retrieved articles were searched for randomized controlled trials (RCTs) and quasi‐RCTs.
It included RCTs and quasi‐RCTs that compared indomethacin (any dose, any route) versus placebo or no treatment in preterm infants. A total of 14 RCTs consisting of 880 preterm infants were included.
Key findings of the study include:
Four out of the 14 included studies were judged to have high risk of bias in one or more domains.
Indomethacin administration was associated with a large reduction in failure of PDA closure within one week of administration of the first dose (risk ratio (RR) 0.30; 10 studies, 654 infants; high‐certainty evidence).
There may be little to no difference in the incidence of BPD (BPD defined as supplemental oxygen need at 28 days' postnatal age: RR 1.45; 1 study, 55 infants; low‐certainty evidence; BPD defined as supplemental oxygen need at 36 weeks' postmenstrual age: RR 0.80; 1 study, 92 infants; low‐certainty evidence) and probably little to no difference in mortality (RR 0.78; 8 studies, 314 infants; moderate‐certainty evidence) with use of indomethacin for symptomatic PDA. No differences were demonstrated in the need for surgical PDA ligation (RR 0.66; 7 studies, 275 infants; moderate‐certainty evidence), in NEC (RR 1.27; 2 studies, 147 infants; low‐certainty evidence), or in mucocutaneous or gastrointestinal bleeding (RR 0.33; 2 studies, 119 infants; low‐certainty evidence) with use of indomethacin compared to placebo or no treatment.
Certainty of evidence for BPD, surgical PDA ligation, NEC, and mucocutaneous or gastrointestinal bleeding was downgraded for very serious or serious imprecision.
"High‐certainty evidence shows that indomethacin is effective in closing a symptomatic PDA compared to placebo or no treatment in preterm infants. Evidence is insufficient regarding effects of indomethacin on other clinically relevant outcomes and medication‐related adverse effects," wrote the authors.
The review titled, "Indomethacin for symptomatic patent ductus arteriosus in preterm infants," is published in Cochrane Library.
DOI: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013133.pub2/full