Prophylactic Intravenous Acetaminophen in Extremely Premature Infants: Minimum Effective Dose Research by Bayesian Approach
Bouazza, Naïm; Cambonie, Gilles; Flamant, Cyril; Rideau, Aline; Tauzin, Manon; Patkai, Juliana; Gascoin, Géraldine; Lumia, Mirka; Aikio, Outi; Lui, Gabrielle; Bournaud, Léo Froelicher; Walsh-Papageorgiou, Aisling; Tortigue, Marine; Baruteau, Alban-Elouen; Kallio, Jaana; Hallman, Mikko; Diallo, Alpha; Levoyer, Léa; Treluyer, Jean-Marc; Roze, Jean-Christophe (2023-11-17)
Bouazza, Naïm
Cambonie, Gilles
Flamant, Cyril
Rideau, Aline
Tauzin, Manon
Patkai, Juliana
Gascoin, Géraldine
Lumia, Mirka
Aikio, Outi
Lui, Gabrielle
Bournaud, Léo Froelicher
Walsh-Papageorgiou, Aisling
Tortigue, Marine
Baruteau, Alban-Elouen
Kallio, Jaana
Hallman, Mikko
Diallo, Alpha
Levoyer, Léa
Treluyer, Jean-Marc
Roze, Jean-Christophe
Springer
17.11.2023
Bouazza, N., Cambonie, G., Flamant, C. et al. Prophylactic Intravenous Acetaminophen in Extremely Premature Infants: Minimum Effective Dose Research by Bayesian Approach. Pediatr Drugs 26, 83–93 (2024). https://doi.org/10.1007/s40272-023-00602-w
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© The Author(s) 2023. This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
https://creativecommons.org/licenses/by-nc/4.0/
© The Author(s) 2023. This article is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License, which permits any non-commercial use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by-nc/4.0/.
https://creativecommons.org/licenses/by-nc/4.0/
Julkaisun pysyvä osoite on
https://urn.fi/URN:NBN:fi:oulu-202401221392
https://urn.fi/URN:NBN:fi:oulu-202401221392
Tiivistelmä
Abstract
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.
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.
Kokoelmat
- Avoin saatavuus [32889]