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. (Institut d'Investigació Biomèdica de Bellvitge)
Gudiol, Carlota (Institut Català d'Oncologia)
Arnan, Montserrat (Institut d'Investigació Biomèdica de Bellvitge)
Puerta-Alcalde, Pedro (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Carmona-Torre, F. (Clínica Universidad de Navarra)
Huguet, Maria (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Albasanz-Puig, Adaia (Spanish Network for Research in Infectious Diseases)
Parody Porras, Rocío (Institut d'Investigació Biomèdica de Bellvitge)
Garcia-Vidal, Carolina (Institut d'Investigacions Biomèdiques August Pi i Sunyer)
Del Pozo, Jose Luis (Clínica Universidad de Navarra)
Batlle, Montserrat. (Institut Germans Trias i Pujol. Institut de Recerca contra la Leucèmia Josep Carreras)
Tebé, C. (Institut d'Investigació Biomèdica de Bellvitge)
Rigo-Bonnin, R. (Hospital Universitari de Bellvitge)
Muñoz, C. (Institut Català d'Oncologia)
Padullés, A. (Institut d'Investigació Biomèdica de Bellvitge)
Tubau, F. (Institut d'Investigació Biomèdica de Bellvitge)
Videla, S. (Institut d'Investigació Biomèdica de Bellvitge)
Sureda, A. (Institut d'Investigació Biomèdica de Bellvitge)
Carratalà, Jordi (Spanish Network for Research in Infectious Diseases)
Universitat Autònoma de Barcelona

Data:	2020
Resum:	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.
Ajuts:	Instituto de Salud Carlos III PI17-01372
Nota:	Altres ajuts: The BEATLE study is a non-commercial, investigator-driven clinical trial funded by the Spanish Network for Research in Infectious Diseases (REIPI RD16/0016/0005; RD16/0016/0010) The Spanish Clinical Research Network (SCReN) provides clinical trial data monitoring and oversees pharmacovigilance (PT17/0017/0010).
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Cefepime ; Extended infusion ; Febrile neutropaenia ; Meropenem ; Piperacillin-tazobactam Randomised controlled trial ; β-lactam antibiotics
Publicat a:	Trials, Vol. 21 Núm. 1 (18 2020) , p. 412, ISSN 1745-6215

DOI: 10.1186/s13063-020-04323-0
PMID: 32423462

9 p, 703.1 KB

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