Prophylactic Intravenous Acetaminophen in Extremely Premature Infants: Minimum Effective Dose Research by Bayesian Approach.

Autor: Bouazza N; EA 7323, Université Paris Cité, Pharmacologie et évaluations thérapeutiques chez l'enfant et la femme enceinte, Paris, France. naim.bouazza@aphp.fr.; Unité de Recherche Clinique, Université Paris Cité Necker/Cochin, Hôpital Tarnier, Paris, France. naim.bouazza@aphp.fr.; CIC-1419 Inserm, Cochin-Necker, Paris, France. naim.bouazza@aphp.fr., Cambonie G; Department of Neonatal Medicine and Pediatric Intensive Care, Arnaud de Villeneuve Hospital, Montpellier University Hospital, 371 Avenue du Doyen Giraud, 34295, Montpellier, France.; Pathogenesis and Control of Chronic Infection, INSERM, UMR 1058, University of Montpellier, Montpellier, France., Flamant C; Department of Neonatology, CHU Nantes, Nantes, France., Rideau A; Department of Pediatrics, Robert Debré Hospital, APHP, Paris, France., Tauzin M; Neonatal Intensive Care Unit, Centre Hospitalier Intercommunal de Créteil, Créteil, France., Patkai J; Neonatology Department, Port-Royal Hospital, 75014, Paris, France., Gascoin G; Department of Neonatology, Angers University Hospital, Angers, France., Lumia M; Department of Children and Adolescents, New Children's Hospital, Pediatric Research Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland., Aikio O; Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, and Research Unit of Clinical Medicine and MRC Oulu, University of Oulu, Oulu, Finland., Lui G; Service de Pharmacologie Clinique, Hôpital Cochin, AP-HP, Groupe Hospitalier Paris Centre, Paris, France., Bournaud LF; Service de Pharmacologie Clinique, Hôpital Cochin, AP-HP, Groupe Hospitalier Paris Centre, Paris, France., Walsh-Papageorgiou A; European Foundation for the Care of Newborn Infants, Munich, Germany., Tortigue M; Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France.; Department of Pediatric Cardiology and Pediatric Cardiac Surgery, FHU PRECICARE, Nantes Université, CHU Nantes, Nantes, France.; Nantes Université, CHU Nantes, INSERM, CIC FEA 1413, Nantes, France., Baruteau AE; Nantes Université, CHU Nantes, CNRS, INSERM, l'institut du thorax, Nantes, France.; Department of Pediatric Cardiology and Pediatric Cardiac Surgery, FHU PRECICARE, Nantes Université, CHU Nantes, Nantes, France.; Nantes Université, CHU Nantes, INSERM, CIC FEA 1413, Nantes, France.; Nantes Université, INRAE, UMR 1280, PhAN, Nantes, France., Kallio J; Department of Children and Adolescents, New Children's Hospital, Pediatric Research Center, Helsinki University Hospital and University of Helsinki, Helsinki, Finland., Hallman M; Department of Pediatrics and Adolescent Medicine, Oulu University Hospital, and Research Unit of Clinical Medicine and MRC Oulu, University of Oulu, Oulu, Finland., Diallo A; Clinical Trial Safety and Public Health, ANRS|Emerging Infectious Diseases, Paris, France.; Clinical Research Safety Department, INSERM, Paris, France., Levoyer L; Clinical Trial Safety and Public Health, ANRS|Emerging Infectious Diseases, Paris, France.; Clinical Research Safety Department, INSERM, Paris, France., Treluyer JM; EA 7323, Université Paris Cité, Pharmacologie et évaluations thérapeutiques chez l'enfant et la femme enceinte, Paris, France.; Unité de Recherche Clinique, Université Paris Cité Necker/Cochin, Hôpital Tarnier, Paris, France.; CIC-1419 Inserm, Cochin-Necker, Paris, France.; Service de Pharmacologie Clinique, Hôpital Cochin, AP-HP, Groupe Hospitalier Paris Centre, Paris, France., Roze JC; Nantes Université, CHU Nantes, INSERM, CIC FEA 1413, Nantes, France.; Nantes Université, INRAE, UMR 1280, PhAN, Nantes, France.
Jazyk: angličtina
Zdroj: Paediatric drugs [Paediatr Drugs] 2024 Jan; Vol. 26 (1), pp. 83-93. Date of Electronic Publication: 2023 Nov 17.
DOI: 10.1007/s40272-023-00602-w
Abstrakt: Background: Patent ductus arteriosus (PDA) in preterm infants is associated with increased morbidities and mortality. Prophylactic treatment with cyclooxygenase inhibitors, as indomethacin or ibuprofen, failed to demonstrate significant clinical benefits. Acetaminophen may represent an alternative treatment option.
Objective: This study evaluated the minimum effective dose of prophylactic acetaminophen to close the ductus and assessed the safety and tolerability profile in extremely preterm infants at 23-26 weeks of gestation.
Methods: A dose finding trial with Bayesian continual reassessment method was performed in a multicenter study with premature infants hospitalized in neonatal intensive care unit. Infants of 23-26 weeks of gestation and post-natal age ≤ 12 h were enrolled. Four intravenous acetaminophen dose levels were predefined. The primary outcome was the ductus arteriosus closing at two consecutive echocardiographies or at day 7. The main secondary objectives included the safety of acetaminophen on hemodynamics and biological hepatic function.
Results: A total of 29 patients were analyzed sequentially for the primary analysis with 20 infants assigned to the first dose level followed by 9 infants to the second dose level. No further dose level increase was necessary. The posterior probabilities of success, estimated from the Bayesian logistic model, were 46.1% [95% probability interval (PI), 24.9-63.9] and 67.6% (95% PI, 51.5-77.9) for dose level 1 and 2, respectively. A closing or closed pattern was observed among 19 patients at the end of treatment [65.5% (95% confidence interval (CI), 45.7-82.0)]. No change in alanine aminotransferase values was observed during treatment. A significant decrease in aspartate aminotransferase values was observed with postnatal age. No change in systolic and diastolic blood pressures was observed during treatment.
Conclusions: Minimum effective dose to close the ductus was 25 mg/kg loading dose then 10 mg/kg/6 h for 5 days in extremely preterm infants. Acetaminophen was well tolerated in this study following these doses.
Trial Registration: ClinicalTrials.gov Identifier: NCT04459117.
(© 2023. The Author(s).)
Databáze: MEDLINE
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