Comparison of Oral Paracetamol versus Ibuprofen in Premature Infants with Patent Ductus Arteriosus: A Randomized Controlled Trial

PLOS ONE, Dec 2019

Trial Design Oral ibuprofen has demonstrated good effects on symptomatic patent ductus arteriosus (PDA) but with many contraindications and potential side-effects. In the past two years, oral paracetamol administration to several preterm infants with PDA has been reported. Here, a randomized, non-blinded, parallel-controlled and non-inferiority trial was designed to evaluate the efficacy and safety profiles of oral paracetamol to those of standard ibuprofen for PDA closure in premature infants. Methods One hundred and sixty infants (gestational age ≤34 weeks) with echocardiographically confirmed PDA were randomly assigned to receive either oral paracetamol (n = 80) or ibuprofen (n = 80). After the initial treatment course in both groups, the need for a second course was determined by echocardiographic evaluation. The main outcome was rate of ductal closure, and secondary outcomes were adverse effects and complications. Result The ductus was closed in 65 (81.2%) infants of the paracetamol group compared with 63 (78.8%) of the ibuprofen group. The 95% confidence interval of the difference between these groups was [−0.080,0.128], demonstrating that the effectiveness of paracetamol treatment was not inferior to that of ibuprofen. In fact, the incidence of hyperbilirubinemia or gastrointestinal bleeding in the paracetamol group was significantly lower than that of the ibuprofen group. No significant differences in other clinical side effects or complications were noted. Conclusion This comparison of drug efficacy and safety profiles in premature infants with PDA revealed that oral paracetamol was comparable to ibuprofen in terms of the rate of ductal closure and even showed a decreased risk of hyperbilirubinemia or gastrointestinal bleeding. Therefore, paracetamol may be accepted as a first-line drug treatment for PDA in preterm infants. Trial Registration ChiCTR.org ChiCTR-TRC-12002177

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Comparison of Oral Paracetamol versus Ibuprofen in Premature Infants with Patent Ductus Arteriosus: A Randomized Controlled Trial

et al. (2013) Comparison of Oral Paracetamol versus Ibuprofen in Premature Infants with Patent Ductus Arteriosus: A Randomized Controlled Trial. PLoS ONE 8(11): e77888. doi:10.1371/journal.pone.0077888 Comparison of Oral Paracetamol versus Ibuprofen in Premature Infants with Patent Ductus Arteriosus: A Randomized Controlled Trial Dan Dang 0 Dongxuan Wang 0 Chuan Zhang 0 Wenli Zhou 0 Qi Zhou 0 Hui Wu 0 Imti Choonara, Nottingham University, United Kingdom 0 1 Department of Neonatology, The First Hospital of Jilin University , Changchun , China , 2 Department of Ultrasonic Diagnosis, The First Hospital of Jilin University , Changchun , China , 3 Department of Pediatric Surgery, The First Hospital of Jilin University , Changchun , China Trial Design: Oral ibuprofen has demonstrated good effects on symptomatic patent ductus arteriosus (PDA) but with many contraindications and potential side-effects. In the past two years, oral paracetamol administration to several preterm infants with PDA has been reported. Here, a randomized, non-blinded, parallel-controlled and non-inferiority trial was designed to evaluate the efficacy and safety profiles of oral paracetamol to those of standard ibuprofen for PDA closure in premature infants. Methods: One hundred and sixty infants (gestational age #34 weeks) with echocardiographically confirmed PDA were randomly assigned to receive either oral paracetamol (n = 80) or ibuprofen (n = 80). After the initial treatment course in both groups, the need for a second course was determined by echocardiographic evaluation. The main outcome was rate of ductal closure, and secondary outcomes were adverse effects and complications. Result: The ductus was closed in 65 (81.2%) infants of the paracetamol group compared with 63 (78.8%) of the ibuprofen group. The 95% confidence interval of the difference between these groups was [20.080,0.128], demonstrating that the effectiveness of paracetamol treatment was not inferior to that of ibuprofen. In fact, the incidence of hyperbilirubinemia or gastrointestinal bleeding in the paracetamol group was significantly lower than that of the ibuprofen group. No significant differences in other clinical side effects or complications were noted. Conclusion: This comparison of drug efficacy and safety profiles in premature infants with PDA revealed that oral paracetamol was comparable to ibuprofen in terms of the rate of ductal closure and even showed a decreased risk of hyperbilirubinemia or gastrointestinal bleeding. Therefore, paracetamol may be accepted as a first-line drug treatment for PDA in preterm infants. Trial Registration: ChiCTR.org ChiCTR-TRC-12002177 PLOS ONE | www.plosone.org - Funding: The trial Comparison of Oral Paracetamol versus Ibuprofen in Premature Infants with Patent Ductus Arteriosus: A Randomized Controlled Trial was funded from Jilin Department of Health (2012Z033). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing Interests: The authors have declared that no competing interests exist. Patent ductus arteriosus (PDA) in preterm infants is common, with an incidence rate as high as 30% in very low birth weight infants. [1] Persistent PDA in preterm infants can lead to serious clinical consequences, and it is one of the main factors affecting the survival rate of premature children and sequelae incidence. [2,3] Consequently, clinical intervention to promote ductal closure is necessary. Currently, the first choice of treatment for PDA is with medication, primarily indomethacin and ibuprofen. The ductal closure rates for these drugs are similar, ranging from approximately 7085%, [4,5] but they carry many contraindications and potential side effects.[611] When drug treatment fails, clinicians may resort to surgical intervention of symptomatic PDA in preterm infants, and the risk of complications from the operation is high. [12,13] Therefore, a safe and effective alternative drug for the treatment of PDA is urgently needed. Recent studies have shown that paracetamol, a common antipyretic and analgesic drug, can be used to treat PDA in preterm infants with good efficacy and seemingly few side effects. [14] However, it has not been evaluated in a prospective randomized controlled trial. To determine whether oral paracetamol may be used as a first-line drug for PDA in preterm infants, we conducted a randomized, non-blinded, parallel-controlled, non-inferiority trial to compare its efficacy and safety levels to those of ibuprofen. The findings are expected to help extend clinical selections for PDA in preterm infants. Patients and Methods Patients The trial was entered in the Chinese Clinical Trial Register (http://www.chictr.org/cn/registration number: ChiCTR-TRC12002177) and approved by the Hospital Ethics Committee of the First Hospital of Jilin University (No.2012-057). Informed written consent was obtained from parents of the subjects before e (...truncated)


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Dan Dang, Dongxuan Wang, Chuan Zhang, Wenli Zhou, Qi Zhou, Hui Wu. Comparison of Oral Paracetamol versus Ibuprofen in Premature Infants with Patent Ductus Arteriosus: A Randomized Controlled Trial, PLOS ONE, 2013, Volume 8, Issue 11, DOI: 10.1371/journal.pone.0077888