Clinical trial NCT04233996: Efficacy of Extended Infusion of β-lactam Antibiotics for the Treatment of Febrile Neutropenia in Hematologic Patients
Official title: Efficacy of Extended Infusion of β-lactam Antibiotics for the Treatment of Febrile Neutropenia in Haematologic Patients: a Randomised, Multicentre, Open-label, Superiority Clinical Trial (BEATLE)
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Febrile Neutropenia
Keywords: Febrile neutropenia
Beta-lactam antibiotics
Cefepime
Meropenem
Piperacillin-tazobactam
Extended infusion
Lead sponsor: Hospital Universitari de Bellvitge
Sponsor class: OTHER
Collaborators: name: Institut d'Investigació Biomèdica de Bellvitge
name: Instituto de Salud Carlos III
First posted: 2020-01-21
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study evaluates the administration of beta-lactam antibiotics in extended infusion in hematological patients with febrile neutropenia after 5 days of treatment. The beta-lactam antibiotics analyzed are the following: piperacillin-tazobactam, cefepime and meropenem. Half of patients will receive the antibiotic in intermittent infusion, while the other half will receive it in extended infusion.

Detailed description: Febrile neutropenia (FN) is a very frequent complication in patients with hematological malignancies. It is associated with an important morbidity and mortality. Nowadays the use of betalactam antibiotics (BLA) in extended or continuous infusion (EI, CI) instead of intermittent infusion (II), has demonstrated a therapeutic success and lower mortality rate in critically ill intensive care patients. Neutropenic patients are a particular population since FN is assoicated with pathophysiological variations that compromise pharmacokinetic parameters of BLA, and may therefore, diminish their clinical efficacy. Information regarding the usefulness of BLA in EI in neutropenic hematologic patients is scarce.

The objective of this randomized clinical trial is to demonstrate the clinical superiority of the administration of BLA in EI compared to II in patients with FN.

Eligibility criteria: Inclusion Criteria:

1. Adult patients (age ≥18 years) of both sexes.
2. Patients admitted in Hematological wards.
3. With any of the following diagnoses:

   1. Acute leukemia receiving chemotherapy.
   2. Autologous or allogeneic hematopoietic stem cell transplant recipients.
4. With an episode of febrile neutropenia: ≥ 38.0ºC and \<500 neutrophils/mm3 or \<1000 with a predicted decrease within 24-48 hours.
5. Patient requiring treatment with a beta-lactam antibiotic: cefepime, piperacillin /tazobactam or meropenem, in monotherapy or in combination with another antibiotic.
6. Written informed consent has been obtained from the patient or their legal representative grants.

Exclusion Criteria:

1. Allergy to study drugs.
2. Patient receiving systemic antibiotic treatment (except for prophylaxis) at the time of onset of febrile neutropenia.
3. Absence of fever.
4. Patients with epilepsy.
5. Severe renal impairment (defined as creatinine clearance \<30 mL / min)
6. Previously enrolled patients in whom the time between the inclusion and the current episode is less than 5 weeks.
7. Previously enrolled patients without current resolution of the first episode.

Primary outcomes:
measure: Clinical efficacy of extended infusion: Number of patients with defervescence
timeFrame: 5 days
Secondary outcomes:
measure: Pharmacokinetic target
timeFrame: 5 days
measure: Inflammatory biomarker
timeFrame: 5 days
measure: Overall mortality at 30 days
timeFrame: 30 days
measure: Bacteraemia clearance
timeFrame: 30 days
measure: Adverse events
timeFrame: 30 days
measure: Pharmacokinetic analysis and population pharmacokinetics of meropenem, piperacillin and cefepime in neutropenic patients: Volume of distribution
timeFrame: 5 days
measure: Pharmacokinetic analysis and population pharmacokinetics of meropenem, piperacillin and cefepime in neutropenic patients: Clearance
timeFrame: 5 days
measure: Covariables analysis: biometric values: weight
timeFrame: 5 days
measure: Covariables analysis: biometric values: age
timeFrame: 5 days
measure: Covariables analysis: biochemical data: serum albumin
timeFrame: 5 days
measure: Covariables analysis: biochemical data: blood urea
timeFrame: 5 days
measure: Covariables analysis: biochemical data: blood creatinine
timeFrame: 5 days
measure: Covariables analysis: clinical data: 24h diuresis
timeFrame: 5 days
measure: Pharmacokinetic analysis and population pharmacokinetics: time above a critical concentration value for plasma concentrations
timeFrame: 5 days
Other outcomes:
Locations:
city: Hospitalet de Llobregat
country: Spain
facility: Hospital Duran i Reynals
state: Barcelona
Study officials:
affiliation: Hospital Universitari de Bellvitge
name: Carlota Gudiol, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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 JL, Batlle M, Tebe C, Rigo-Bonnin R, Munoz C, Padulles A, Tubau F, Videla S, Sureda A, Carratala J. Efficacy of extended infusion of beta-lactam antibiotics for the treatment of febrile neutropenia in haematologic patients: protocol for a randomised, multicentre, open-label, superiority clinical trial (BEATLE). Trials. 2020 May 18;21(1):412. doi: 10.1186/s13063-020-04323-0.