Cargando…

Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients: protocol for a randomised, multicentre, open-label, superiority clinical trial (BEATLE)

BACKGROUND: Febrile neutropaenia (FN) is a very common complication in patients with haematological malignancies and is associated with considerable morbidity and mortality. Broad-spectrum antipseudomonal β-lactam antibiotics (BLA) are routinely used for the treatment of cancer patients with FN. How...

Descripción completa

Detalles Bibliográficos
Autores principales: Laporte-Amargos, J., Gudiol, C., Arnan, M., Puerta-Alcalde, P., Carmona-Torre, F., Huguet, M., Albasanz-Puig, A., Parody, R., Garcia-Vidal, C., del Pozo, J. L., Batlle, M., Tebé, C., Rigo-Bonnin, R., Muñoz, C., Padullés, A., Tubau, F., Videla, S., Sureda, A., Carratalà, J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236103/
https://www.ncbi.nlm.nih.gov/pubmed/32423462
http://dx.doi.org/10.1186/s13063-020-04323-0
_version_ 1783536092976250880
author Laporte-Amargos, J.
Gudiol, C.
Arnan, M.
Puerta-Alcalde, P.
Carmona-Torre, F.
Huguet, M.
Albasanz-Puig, A.
Parody, R.
Garcia-Vidal, C.
del Pozo, J. L.
Batlle, M.
Tebé, C.
Rigo-Bonnin, R.
Muñoz, C.
Padullés, A.
Tubau, F.
Videla, S.
Sureda, A.
Carratalà, J.
author_facet Laporte-Amargos, J.
Gudiol, C.
Arnan, M.
Puerta-Alcalde, P.
Carmona-Torre, F.
Huguet, M.
Albasanz-Puig, A.
Parody, R.
Garcia-Vidal, C.
del Pozo, J. L.
Batlle, M.
Tebé, C.
Rigo-Bonnin, R.
Muñoz, C.
Padullés, A.
Tubau, F.
Videla, S.
Sureda, A.
Carratalà, J.
author_sort Laporte-Amargos, J.
collection PubMed
description BACKGROUND: Febrile neutropaenia (FN) is a very common complication in patients with haematological malignancies and is associated with considerable morbidity and mortality. Broad-spectrum antipseudomonal β-lactam antibiotics (BLA) are routinely used for the treatment of cancer patients with FN. However, the clinical efficacy of BLA may be diminished in these patients because they present with pathophysiological variations that compromise the pharmacokinetic (PK) parameters of these antibiotics. Optimised administration of BLA in prolonged infusions has demonstrated better clinical outcomes in critically ill patients. However, there is a paucity of data on the usefulness of this strategy in patients with FN. The aim of this study is to test the hypothesis that the administration of BLA would be clinically more effective by extended infusion (EI) than by intermittent infusion (II) in haematological patients with FN. METHODS: A randomised, multicentre, open-label, superiority clinical trial will be performed. Patients with haematological malignancies undergoing chemotherapy or haematopoietic stem-cell transplant and who have FN and receive empirical antibiotic therapy with cefepime, piperacillin-tazobactam or meropenem will be randomised (1:1) to receive the antibiotic by EI (during half the time of the dosing interval) in the study group, or by II (30 min) in the control group. The primary endpoint will be clinical efficacy, defined as defervescence without modifying the antibiotic treatment administered within the first 5 days of therapy. The primary endpoint will be analysed in the intention-to-treat population. The secondary endpoints will be pharmacokinetic/pharmacodynamic (PK/PD) target achievement, bacteraemia clearance, decrease in C-reactive protein, overall (30-day) case-fatality rate, adverse events and development of a population PK model of the BLA studied. DISCUSSION: Data on the usefulness of BLA administration in patients with FN are scant. Only three clinical studies addressing this issue have been published thus far, with contradictory results. Moreover, these studies had some methodological flaws that limit the interpretation of their findings. If this randomised, multicentre, phase IV, open-label, superiority clinical trial validates the hypothesis that the administration of BLA is clinically more effective by EI than by II in haematological patients with FN, then the daily routine management of these high-risk patients could be changed to improve their outcomes. TRIAL REGISTRATION: European Clinical Trials Database: EudraCT 2018–001476-37. ClinicalTrials.gov, ID: NCT04233996.
format Online
Article
Text
id pubmed-7236103
institution National Center for Biotechnology Information
language English
publishDate 2020
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-72361032020-05-27 Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients: protocol for a randomised, multicentre, open-label, superiority clinical trial (BEATLE) Laporte-Amargos, J. Gudiol, C. Arnan, M. Puerta-Alcalde, P. Carmona-Torre, F. Huguet, M. Albasanz-Puig, A. Parody, R. Garcia-Vidal, C. del Pozo, J. L. Batlle, M. Tebé, C. Rigo-Bonnin, R. Muñoz, C. Padullés, A. Tubau, F. Videla, S. Sureda, A. Carratalà, J. Trials Study Protocol BACKGROUND: Febrile neutropaenia (FN) is a very common complication in patients with haematological malignancies and is associated with considerable morbidity and mortality. Broad-spectrum antipseudomonal β-lactam antibiotics (BLA) are routinely used for the treatment of cancer patients with FN. However, the clinical efficacy of BLA may be diminished in these patients because they present with pathophysiological variations that compromise the pharmacokinetic (PK) parameters of these antibiotics. Optimised administration of BLA in prolonged infusions has demonstrated better clinical outcomes in critically ill patients. However, there is a paucity of data on the usefulness of this strategy in patients with FN. The aim of this study is to test the hypothesis that the administration of BLA would be clinically more effective by extended infusion (EI) than by intermittent infusion (II) in haematological patients with FN. METHODS: A randomised, multicentre, open-label, superiority clinical trial will be performed. Patients with haematological malignancies undergoing chemotherapy or haematopoietic stem-cell transplant and who have FN and receive empirical antibiotic therapy with cefepime, piperacillin-tazobactam or meropenem will be randomised (1:1) to receive the antibiotic by EI (during half the time of the dosing interval) in the study group, or by II (30 min) in the control group. The primary endpoint will be clinical efficacy, defined as defervescence without modifying the antibiotic treatment administered within the first 5 days of therapy. The primary endpoint will be analysed in the intention-to-treat population. The secondary endpoints will be pharmacokinetic/pharmacodynamic (PK/PD) target achievement, bacteraemia clearance, decrease in C-reactive protein, overall (30-day) case-fatality rate, adverse events and development of a population PK model of the BLA studied. DISCUSSION: Data on the usefulness of BLA administration in patients with FN are scant. Only three clinical studies addressing this issue have been published thus far, with contradictory results. Moreover, these studies had some methodological flaws that limit the interpretation of their findings. If this randomised, multicentre, phase IV, open-label, superiority clinical trial validates the hypothesis that the administration of BLA is clinically more effective by EI than by II in haematological patients with FN, then the daily routine management of these high-risk patients could be changed to improve their outcomes. TRIAL REGISTRATION: European Clinical Trials Database: EudraCT 2018–001476-37. ClinicalTrials.gov, ID: NCT04233996. BioMed Central 2020-05-18 /pmc/articles/PMC7236103/ /pubmed/32423462 http://dx.doi.org/10.1186/s13063-020-04323-0 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits 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/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Study Protocol
Laporte-Amargos, J.
Gudiol, C.
Arnan, M.
Puerta-Alcalde, P.
Carmona-Torre, F.
Huguet, M.
Albasanz-Puig, A.
Parody, R.
Garcia-Vidal, C.
del Pozo, J. L.
Batlle, M.
Tebé, C.
Rigo-Bonnin, R.
Muñoz, C.
Padullés, A.
Tubau, F.
Videla, S.
Sureda, A.
Carratalà, J.
Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients: protocol for a randomised, multicentre, open-label, superiority clinical trial (BEATLE)
title Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients: protocol for a randomised, multicentre, open-label, superiority clinical trial (BEATLE)
title_full Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients: protocol for a randomised, multicentre, open-label, superiority clinical trial (BEATLE)
title_fullStr Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients: protocol for a randomised, multicentre, open-label, superiority clinical trial (BEATLE)
title_full_unstemmed Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients: protocol for a randomised, multicentre, open-label, superiority clinical trial (BEATLE)
title_short Efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients: protocol for a randomised, multicentre, open-label, superiority clinical trial (BEATLE)
title_sort efficacy of extended infusion of β-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients: protocol for a randomised, multicentre, open-label, superiority clinical trial (beatle)
topic Study Protocol
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7236103/
https://www.ncbi.nlm.nih.gov/pubmed/32423462
http://dx.doi.org/10.1186/s13063-020-04323-0
work_keys_str_mv AT laporteamargosj efficacyofextendedinfusionofblactamantibioticsforthetreatmentoffebrileneutropeniainhaematologicpatientsprotocolforarandomisedmulticentreopenlabelsuperiorityclinicaltrialbeatle
AT gudiolc efficacyofextendedinfusionofblactamantibioticsforthetreatmentoffebrileneutropeniainhaematologicpatientsprotocolforarandomisedmulticentreopenlabelsuperiorityclinicaltrialbeatle
AT arnanm efficacyofextendedinfusionofblactamantibioticsforthetreatmentoffebrileneutropeniainhaematologicpatientsprotocolforarandomisedmulticentreopenlabelsuperiorityclinicaltrialbeatle
AT puertaalcaldep efficacyofextendedinfusionofblactamantibioticsforthetreatmentoffebrileneutropeniainhaematologicpatientsprotocolforarandomisedmulticentreopenlabelsuperiorityclinicaltrialbeatle
AT carmonatorref efficacyofextendedinfusionofblactamantibioticsforthetreatmentoffebrileneutropeniainhaematologicpatientsprotocolforarandomisedmulticentreopenlabelsuperiorityclinicaltrialbeatle
AT huguetm efficacyofextendedinfusionofblactamantibioticsforthetreatmentoffebrileneutropeniainhaematologicpatientsprotocolforarandomisedmulticentreopenlabelsuperiorityclinicaltrialbeatle
AT albasanzpuiga efficacyofextendedinfusionofblactamantibioticsforthetreatmentoffebrileneutropeniainhaematologicpatientsprotocolforarandomisedmulticentreopenlabelsuperiorityclinicaltrialbeatle
AT parodyr efficacyofextendedinfusionofblactamantibioticsforthetreatmentoffebrileneutropeniainhaematologicpatientsprotocolforarandomisedmulticentreopenlabelsuperiorityclinicaltrialbeatle
AT garciavidalc efficacyofextendedinfusionofblactamantibioticsforthetreatmentoffebrileneutropeniainhaematologicpatientsprotocolforarandomisedmulticentreopenlabelsuperiorityclinicaltrialbeatle
AT delpozojl efficacyofextendedinfusionofblactamantibioticsforthetreatmentoffebrileneutropeniainhaematologicpatientsprotocolforarandomisedmulticentreopenlabelsuperiorityclinicaltrialbeatle
AT batllem efficacyofextendedinfusionofblactamantibioticsforthetreatmentoffebrileneutropeniainhaematologicpatientsprotocolforarandomisedmulticentreopenlabelsuperiorityclinicaltrialbeatle
AT tebec efficacyofextendedinfusionofblactamantibioticsforthetreatmentoffebrileneutropeniainhaematologicpatientsprotocolforarandomisedmulticentreopenlabelsuperiorityclinicaltrialbeatle
AT rigobonninr efficacyofextendedinfusionofblactamantibioticsforthetreatmentoffebrileneutropeniainhaematologicpatientsprotocolforarandomisedmulticentreopenlabelsuperiorityclinicaltrialbeatle
AT munozc efficacyofextendedinfusionofblactamantibioticsforthetreatmentoffebrileneutropeniainhaematologicpatientsprotocolforarandomisedmulticentreopenlabelsuperiorityclinicaltrialbeatle
AT padullesa efficacyofextendedinfusionofblactamantibioticsforthetreatmentoffebrileneutropeniainhaematologicpatientsprotocolforarandomisedmulticentreopenlabelsuperiorityclinicaltrialbeatle
AT tubauf efficacyofextendedinfusionofblactamantibioticsforthetreatmentoffebrileneutropeniainhaematologicpatientsprotocolforarandomisedmulticentreopenlabelsuperiorityclinicaltrialbeatle
AT videlas efficacyofextendedinfusionofblactamantibioticsforthetreatmentoffebrileneutropeniainhaematologicpatientsprotocolforarandomisedmulticentreopenlabelsuperiorityclinicaltrialbeatle
AT suredaa efficacyofextendedinfusionofblactamantibioticsforthetreatmentoffebrileneutropeniainhaematologicpatientsprotocolforarandomisedmulticentreopenlabelsuperiorityclinicaltrialbeatle
AT carratalaj efficacyofextendedinfusionofblactamantibioticsforthetreatmentoffebrileneutropeniainhaematologicpatientsprotocolforarandomisedmulticentreopenlabelsuperiorityclinicaltrialbeatle