Ashutosh Kumar1, Rahul Subhash Gosavi2, Venkataseshan Sundaram3, Tejo Pratap Oleti2, Arun Krishnan4, Sai Kiran2, Jogender Kumar5, Srinivas Murki2, Mangalabharathi Sundaram4, Shiv Sajan Saini5, Sourabh Dutta5. 1. Division of Neonatology, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India; Department of Pediatrics, Research and Referral, Army Hospital, New Delhi, India. 2. Department of Neonatology, Fernandez Hospital, Bogulakunta, Hyderabad, India. 3. Division of Neonatology, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Electronic address: venkatpgi@gmail.com. 4. Department of Neonatology, Institute of Child Health, Egmore, Chennai, India. 5. Division of Neonatology, Department of Pediatrics, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
Abstract
OBJECTIVE: To test the hypothesis that oral paracetamol is non-inferior to oral ibuprofen in closing hemodynamically significant patent ductus arteriosus (hsPDA) with an a priori noninferiority (NI) margin of 15%. STUDY DESIGN: Multicenter, randomized, controlled, NI trial conducted in level III neonatal intensive care units. Consecutively inborn preterm neonates of <32 weeks of gestation with hsPDA were included. Those with structural heart disease, major malformations, and contraindications for enteral feeding or for administration of study drugs were excluded. Interventions included oral paracetamol in the experimental arm and oral ibuprofen in the active control arm. The primary outcome was closure of hsPDA by 24 hours from the last dose of the study drug. Secondary outcome measures included closure of hsPDA by 24 hours after the first course of the study drug, rate of reopening after the first course, and adverse events associated with the study drug. RESULTS: Out of 1250 neonates screened, 161 were randomized. Oral paracetamol was noninferior to oral ibuprofen in closure of hsPDA by both per protocol analysis (62 [95.4%] vs 63 [94%]; relative risk [RR], 1.01 [95% CI, 0.94-1.1]; risk difference [RD], 1.4 [95% CI, -6 to 9]; P = .37) and intention-to-treat analysis (63 [89%] vs 65 [89%]; RR, 0.99 [95% CI, 0.89-1.12]; RD, -0.3 [95% CI, -11 to 10]; P = .47). All adverse events were comparable in the 2 study arms. CONCLUSIONS:Oral paracetamol is noninferior to oral ibuprofen for the closure of hsPDA in preterm neonates of <32 weeks of gestation. No difference was observed in the adverse events studied.
RCT Entities:
OBJECTIVE: To test the hypothesis that oral paracetamol is non-inferior to oral ibuprofen in closing hemodynamically significant patent ductus arteriosus (hsPDA) with an a priori noninferiority (NI) margin of 15%. STUDY DESIGN: Multicenter, randomized, controlled, NI trial conducted in level III neonatal intensive care units. Consecutively inborn preterm neonates of <32 weeks of gestation with hsPDA were included. Those with structural heart disease, major malformations, and contraindications for enteral feeding or for administration of study drugs were excluded. Interventions included oral paracetamol in the experimental arm and oral ibuprofen in the active control arm. The primary outcome was closure of hsPDA by 24 hours from the last dose of the study drug. Secondary outcome measures included closure of hsPDA by 24 hours after the first course of the study drug, rate of reopening after the first course, and adverse events associated with the study drug. RESULTS: Out of 1250 neonates screened, 161 were randomized. Oral paracetamol was noninferior to oral ibuprofen in closure of hsPDA by both per protocol analysis (62 [95.4%] vs 63 [94%]; relative risk [RR], 1.01 [95% CI, 0.94-1.1]; risk difference [RD], 1.4 [95% CI, -6 to 9]; P = .37) and intention-to-treat analysis (63 [89%] vs 65 [89%]; RR, 0.99 [95% CI, 0.89-1.12]; RD, -0.3 [95% CI, -11 to 10]; P = .47). All adverse events were comparable in the 2 study arms. CONCLUSIONS: Oral paracetamol is noninferior to oral ibuprofen for the closure of hsPDA in preterm neonates of <32 weeks of gestation. No difference was observed in the adverse events studied.
Authors: David J McCulley; Erik A Jensen; Jennifer M S Sucre; Sarah McKenna; Laura G Sherlock; Evgenia Dobrinskikh; Clyde J Wright Journal: Am J Physiol Lung Cell Mol Physiol Date: 2022-05-03 Impact factor: 6.011
Authors: Ana García-Robles; Ana Gimeno Navarro; María Del Mar Serrano Martín; María José Párraga Quiles; Anna Parra Llorca; José Luis Poveda-Andrés; Máximo Vento Torres; Marta Aguar Carrascosa Journal: Front Pediatr Date: 2020-07-17 Impact factor: 3.418