Cargando…

Latamoxef for Neonates With Early-Onset Neonatal Sepsis: A Study Protocol for a Randomized Controlled Trial

Early-onset neonatal sepsis (EONS), a bacterial infection that occurs within 72 h after birth, is associated with high likelihood of neonatal mortality. Latamoxef, a semi-synthetic oxacephem antibiotic developed in 1980s, has been brought back into empirical EONS treatment in recent years. In the pr...

Descripción completa

Detalles Bibliográficos
Autores principales: Qi, Hui, Wu, Yue-E, Liu, Ya-Li, Kou, Chen, Wang, Ze-Ming, Peng, Xiao-Xia, Chen, Liang, Cui, Hong, Wang, Ya-Juan, Li, Jie-Qiong, Zhao, Wei, Shen, A-Dong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220210/
https://www.ncbi.nlm.nih.gov/pubmed/34177569
http://dx.doi.org/10.3389/fphar.2021.635517
_version_ 1783711100293873664
author Qi, Hui
Wu, Yue-E
Liu, Ya-Li
Kou, Chen
Wang, Ze-Ming
Peng, Xiao-Xia
Chen, Liang
Cui, Hong
Wang, Ya-Juan
Li, Jie-Qiong
Zhao, Wei
Shen, A-Dong
author_facet Qi, Hui
Wu, Yue-E
Liu, Ya-Li
Kou, Chen
Wang, Ze-Ming
Peng, Xiao-Xia
Chen, Liang
Cui, Hong
Wang, Ya-Juan
Li, Jie-Qiong
Zhao, Wei
Shen, A-Dong
author_sort Qi, Hui
collection PubMed
description Early-onset neonatal sepsis (EONS), a bacterial infection that occurs within 72 h after birth, is associated with high likelihood of neonatal mortality. Latamoxef, a semi-synthetic oxacephem antibiotic developed in 1980s, has been brought back into empirical EONS treatment in recent years. In the preliminary work, we established a population pharmacokinetics (PPK) model for latamoxef in Chinese neonates. Moreover, in order to better guide clinical treatment, we conducted dose simulation and found that ascending administration frequency could improve the target rate of 70% of patients having a free antimicrobial drug concentration exceeding the MIC during 70% of the dosing interval (70% fT > MIC). Accordingly, this study is aimed to compare the 70% fT > MIC, efficacy and safety between conventional regimen and PPK model regimen for rational use of latamoxef in EONS treatment. A single-blind, multicenter randomized controlled trial (RCT) for latamoxef will be conducted in Chinese EONS patients. Neonates (≤3 days of age, expected number = 114) admitted to the hospital with the diagnosis of EONS and fulfilling inclusion and exclusion criteria will be randomized (ratio of 1:1) to either a conventional regimen (30 mg/kg q12h) or model regimen (20 mg/kg q8h) latamoxef treatment group for at least 3 days. Primary outcome measure will be 70% fT > MIC and secondary outcome indicators will be the latamoxef treatment failure, duration of antibiotic therapy, changes of white blood cell count (WBC), C-reactive protein (CRP) and procalcitonin (PCT), blood culture results during administration and incidence of adverse event (AE)s. Assessments will be made at baseline, initial stage of latamoxef treatment (18–72 h) and before the end of latamoxef treatment. Ethical approval of our clinical trial has been granted by the ethics committee of the Beijing Children’s Hospital (ID: 2020-13-1). Written informed consent will be obtained from the parents of the participants. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR 2000040064).It is hoped that our study will provide a clinical basis for the rational clinical use of latamoxef in EONS treatment.
format Online
Article
Text
id pubmed-8220210
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-82202102021-06-24 Latamoxef for Neonates With Early-Onset Neonatal Sepsis: A Study Protocol for a Randomized Controlled Trial Qi, Hui Wu, Yue-E Liu, Ya-Li Kou, Chen Wang, Ze-Ming Peng, Xiao-Xia Chen, Liang Cui, Hong Wang, Ya-Juan Li, Jie-Qiong Zhao, Wei Shen, A-Dong Front Pharmacol Pharmacology Early-onset neonatal sepsis (EONS), a bacterial infection that occurs within 72 h after birth, is associated with high likelihood of neonatal mortality. Latamoxef, a semi-synthetic oxacephem antibiotic developed in 1980s, has been brought back into empirical EONS treatment in recent years. In the preliminary work, we established a population pharmacokinetics (PPK) model for latamoxef in Chinese neonates. Moreover, in order to better guide clinical treatment, we conducted dose simulation and found that ascending administration frequency could improve the target rate of 70% of patients having a free antimicrobial drug concentration exceeding the MIC during 70% of the dosing interval (70% fT > MIC). Accordingly, this study is aimed to compare the 70% fT > MIC, efficacy and safety between conventional regimen and PPK model regimen for rational use of latamoxef in EONS treatment. A single-blind, multicenter randomized controlled trial (RCT) for latamoxef will be conducted in Chinese EONS patients. Neonates (≤3 days of age, expected number = 114) admitted to the hospital with the diagnosis of EONS and fulfilling inclusion and exclusion criteria will be randomized (ratio of 1:1) to either a conventional regimen (30 mg/kg q12h) or model regimen (20 mg/kg q8h) latamoxef treatment group for at least 3 days. Primary outcome measure will be 70% fT > MIC and secondary outcome indicators will be the latamoxef treatment failure, duration of antibiotic therapy, changes of white blood cell count (WBC), C-reactive protein (CRP) and procalcitonin (PCT), blood culture results during administration and incidence of adverse event (AE)s. Assessments will be made at baseline, initial stage of latamoxef treatment (18–72 h) and before the end of latamoxef treatment. Ethical approval of our clinical trial has been granted by the ethics committee of the Beijing Children’s Hospital (ID: 2020-13-1). Written informed consent will be obtained from the parents of the participants. This trial is registered in the Chinese Clinical Trial Registry (ChiCTR 2000040064).It is hoped that our study will provide a clinical basis for the rational clinical use of latamoxef in EONS treatment. Frontiers Media S.A. 2021-06-09 /pmc/articles/PMC8220210/ /pubmed/34177569 http://dx.doi.org/10.3389/fphar.2021.635517 Text en Copyright © 2021 Qi, Wu, Liu, Kou, Wang, Peng, Chen, Cui, Wang, Li, Zhao and Shen. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Pharmacology
Qi, Hui
Wu, Yue-E
Liu, Ya-Li
Kou, Chen
Wang, Ze-Ming
Peng, Xiao-Xia
Chen, Liang
Cui, Hong
Wang, Ya-Juan
Li, Jie-Qiong
Zhao, Wei
Shen, A-Dong
Latamoxef for Neonates With Early-Onset Neonatal Sepsis: A Study Protocol for a Randomized Controlled Trial
title Latamoxef for Neonates With Early-Onset Neonatal Sepsis: A Study Protocol for a Randomized Controlled Trial
title_full Latamoxef for Neonates With Early-Onset Neonatal Sepsis: A Study Protocol for a Randomized Controlled Trial
title_fullStr Latamoxef for Neonates With Early-Onset Neonatal Sepsis: A Study Protocol for a Randomized Controlled Trial
title_full_unstemmed Latamoxef for Neonates With Early-Onset Neonatal Sepsis: A Study Protocol for a Randomized Controlled Trial
title_short Latamoxef for Neonates With Early-Onset Neonatal Sepsis: A Study Protocol for a Randomized Controlled Trial
title_sort latamoxef for neonates with early-onset neonatal sepsis: a study protocol for a randomized controlled trial
topic Pharmacology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8220210/
https://www.ncbi.nlm.nih.gov/pubmed/34177569
http://dx.doi.org/10.3389/fphar.2021.635517
work_keys_str_mv AT qihui latamoxefforneonateswithearlyonsetneonatalsepsisastudyprotocolforarandomizedcontrolledtrial
AT wuyuee latamoxefforneonateswithearlyonsetneonatalsepsisastudyprotocolforarandomizedcontrolledtrial
AT liuyali latamoxefforneonateswithearlyonsetneonatalsepsisastudyprotocolforarandomizedcontrolledtrial
AT kouchen latamoxefforneonateswithearlyonsetneonatalsepsisastudyprotocolforarandomizedcontrolledtrial
AT wangzeming latamoxefforneonateswithearlyonsetneonatalsepsisastudyprotocolforarandomizedcontrolledtrial
AT pengxiaoxia latamoxefforneonateswithearlyonsetneonatalsepsisastudyprotocolforarandomizedcontrolledtrial
AT chenliang latamoxefforneonateswithearlyonsetneonatalsepsisastudyprotocolforarandomizedcontrolledtrial
AT cuihong latamoxefforneonateswithearlyonsetneonatalsepsisastudyprotocolforarandomizedcontrolledtrial
AT wangyajuan latamoxefforneonateswithearlyonsetneonatalsepsisastudyprotocolforarandomizedcontrolledtrial
AT lijieqiong latamoxefforneonateswithearlyonsetneonatalsepsisastudyprotocolforarandomizedcontrolledtrial
AT zhaowei latamoxefforneonateswithearlyonsetneonatalsepsisastudyprotocolforarandomizedcontrolledtrial
AT shenadong latamoxefforneonateswithearlyonsetneonatalsepsisastudyprotocolforarandomizedcontrolledtrial