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Effectiveness of Dual Medication Therapy (Oral Acetaminophen and Oral Ibuprofen) for the Management of Patent Ductus Arteriosus in Extremely Premature Infants: A Feasibility TrialFunding None.
Objective The study aimed to evaluate the efficacy of dual medication therapy (DMT) with oral acetaminophen and oral ibuprofen for the closure of a hemodynamically significant patent ductus arteriosus (hsPDA).
Study Design In a prospective case–control cohort study (July 2017–May 2019), infants <29 weeks' gestational age and birth weight <1,000 g at ≤14 postnatal days with hsPDA and ratio of the smallest ductal diameter to the ostium of the left pulmonary artery diameter >0.5 were eligible. Infants received 10 mg/kg oral ibuprofen followed by two additional doses of 5 mg/kg at 24 and 48 hours after the initial ibuprofen dose and concomitant treatment with 15 mg/kg oral acetaminophen every 6 hours for 3 days (12 doses). Success of PDA treatment was defined as a small or absent PDA as ascertained by echocardiographic measurements. The p-values of comparisons were adjusted for multiple comparisons to preserve an error rate of 5%.
Results Overall, 20 infants received oral DMT and 11 infants received intravenous single medication therapy (SMT) with ibuprofen. The rates of successful PDA treatment following the first treatment in DMT and SMT groups were not statistically different (11/20 [55%] vs. 4/11 [36%], p = 0.46). However, DMT significantly decreased PDA size (mean difference = 0.54 mm, 95% confidence interval [CI]: 0.21–0.96, adjusted p-value = 0.0002) and PDA/LPA ratio (mean difference = 0.27, 95% CI: 0.10–0.47, adjusted p-value = 0.0004). We observed no evidence of hematologic, hepatic, or renal impairment.
Conclusion DMT achieved a greater degree of PDA closure than SMT and did not result in abnormalities in hepatic and renal profile.
No consensus on optimal medication for PDA treatment is available.
Dual oral medication therapy (ibuprofen and acetaminophen) could be an effective alternative treatment for PDA.
Dual oral medication therapy (ibuprofen and acetaminophen) may have a better safety profile than currently approved medications such as intravenous indomethacin and intravenous ibuprofen.
The portion of the study was presented at the Pediatric Academic Societies meeting from April 24 to May 1, 2019 at Baltimore, MD.
Received: 11 June 2020
Accepted: 20 November 2020
17 January 2021 (online)
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