Paracetamol vs. Ibuprofen in Preterm Infants With Hemodynamically Significant Patent Ductus Arteriosus: A Non-inferiority Randomized Clinical Trial Protocol

Abstract

This is a non-inferiority, randomized, multicenter, double-blinded study to evaluate the efficacy, and safety of intravenous (IV) paracetamol vs. IV ibuprofen (standard treatment) for PDA in preterm patients with a gestational age ≤30 weeks. At baseline, patients will be randomized (1:1) to treatment with paracetamol or ibuprofen. The primary endpoint is closure of the ductus after the first treatment course. Secondary endpoints are related to effectiveness (need for a second treatment course, rescue treatment, reopening rate, time to definitive closure, need for surgical ligation), safety (early and long-term complications), pharmacokinetics, and pharmacodynamics, pharmacogenetics, pharmacoeconomics, and genotoxicity. Long-term follow-up to 24 months of corrected postnatal age will be performed using Bayley III neurodevelopmental scale.

Prophylactic Low-Dose Paracetamol Administration for Ductal Closure and Amplitude-Integrated Electroencephalography in Preterm Infants

“…Patent ductus arteriosus (PDA) is observed in more than 30% of preterm infants with a gestational age of 32 weeks ( 1 ). Cyclooxygenase inhibitors are the therapeutics of choice to induce ductal closure in preterm infants, but they also carry substantial risks that may outweigh the benefit ( 2 – 4 ). Despite a large body of research, there is controversy about the management of ductal closure in preterm infants ( 5 ).…”

Efficacy and Safety of Oral Acetaminophen for Premature Infants With Patent Ductus Arteriosus: A Meta-Analysis

“…4) Only one RCT was included in subgroups II, III, and IV, which may have affected the quality of our results. García-Robles et al (2020) are currently conducting a multicenter RCT on the effects of intravenous acetaminophen and intravenous ibuprofen, further meta-analysis of this subgroup can be conducted after the completion of the study ( García-Robles et al, 2020 ).…”

Efficacy of Paracetamol Compared to Ibuprofen on Closure of Patent Ductus Arteriosus in Premature Infants

“…Insiden kegagalan DA untuk menutup setelah lahir berbanding terbalik dengan usia kehamilan, dengan insiden mulai dari 10% hingga 20% pada bayi prematur >32 minggu hingga 60% pada usia gestasi <28 minggu. 1 Di Indonesia, insiden PDA pada bayi prematur ialah 14%. Kehadiran PDA lebih sering terjadi pada bayi low birth weight (LBW).…”

“…Peran parasetamol sebagai pengobatan alternatif untuk penutupan PDA telah mendapat perhatian karena adanya efek samping potensial dari inhibitor COX. 1,4 Parasetamol juga menghambat aktivitas prostaglandin sintetase melalui kerja pada segmen peroksidase dari enzim yang menyebabkan pengurangan sintesis PG. Selain itu, parasetamol memiliki keuntungan terapeutik dibandingkan NSAID lainnya karena tidak memiliki efek vasokonstriksi perifer.…”