Efficacy of extended infusion of ß-lactam antibiotics for the treatment of febrile neutropenia in hematologic patients (BEATLE study).

Conditions

Febrile neutropenia is the presence of fever in compramised immune activity in patients with hematologic disease. In which case, an antibiotic must be started. MedDRA version: 20.0 Level: LLT Classification code 10029357 Term: Neutropenia malignant System Organ Class: 100000004851

Júlia Laporte-Amargós, Carlota Gudiol, Montserrat Arnán, Pedro Puerta‐Alcalde, Francisco Carmona-Torre et al. (19 authors)

Trials2020-05-1812 citations

10.1186/s13063-020-04323-0

Interventions

Product Name: Piperacilina Pharmaceutical Form: Powder for solution for injection INN or Proposed INN: PIPERACILLIN CAS Number: 66258-76-2

Eligibility

Sex/Gender

All

Inclusion criteria

Inclusion criteria: 1)Adult patients (age =18 years) of both sexes 2)Patients admitted in Hematological ward 3) With any of the following diagnoses: 3.1)Acute leukemia undergoing induction or consolidation chemotherapy 3.2)Autologous or allogeneic hematopoietic stem cell transplant recipients 4) With an episode of Febrile Neutropenia: = 38.0ºC and =65 years) yes F.1.3.1 Number of subjects for this age range 44

Exclusion criteria

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 rate MDR / CKD-EPI <30 mL / min) 6) Previously enrolled patients in whom the time between the inclusion and the current episode is less than 5 weeks 7) Patients who have participated previously in this trial without current resolution of the first episode.

Design outcomes

Primary

Measure	Time frame
Timepoint(s) of evaluation of this end point: During the 5 days of treatment with ABL, and without modification of the antibiotic treatment.;Main Objective: To study the clinical efficacy of extended infusion (EI) of BLA in the patient with febrile neutropenia.; Secondary Objective: 1) Clinical Objectives: 1.1)To determine if the administration of BLA in EI is superior to the administration in II in reaching the PK/PD target in hematological patients with febrile neutropenia. 1.2)To determine if the administration of BLA in EI is superior to the administration in II, defined by the time to the normalization/significant decrease in the inflammatory biomarkers. 1.3)To determine the 30-day overall case-fatality rate of the study population, according to therapy group. 1.4)Develop a pharmacokinetic / pharmacodynamic model to optimize BLA treatment in patients with febrile neutropenia 2)Microbiological Objective: 2.1)To determine if the administration of BLA in EI is superior to the administration in II in the rapidity of negativization of blood cultures in patients with bacteremia. 3)Security Objectives: 3.1)PENDIENTE DE TRADUCIR ;Primary end point(s): Number of responding patients. Responder is defined as a patient with defervescence (axillary temperature <37.5ºC, for 24 hours and documented in a minimum of 3 determinations, without reappearance of fever) during the first 5 days of treatment with ABL and without a modification of the antibiotic treatment.	—

Measure

Time frame

Timepoint(s) of evaluation of this end point: During the 5 days of treatment with ABL, and without modification of the antibiotic treatment.;Main Objective: To study the clinical efficacy of extended infusion (EI) of BLA in the patient with febrile neutropenia.; Secondary Objective: 1) Clinical Objectives: 1.1)To determine if the administration of BLA in EI is superior to the administration in II in reaching the PK/PD target in hematological patients with febrile neutropenia. 1.2)To determine if the administration of BLA in EI is superior to the administration in II, defined by the time to the normalization/significant decrease in the inflammatory biomarkers. 1.3)To determine the 30-day overall case-fatality rate of the study population, according to therapy group. 1.4)Develop a pharmacokinetic / pharmacodynamic model to optimize BLA treatment in patients with febrile neutropenia 2)Microbiological Objective: 2.1)To determine if the administration of BLA in EI is superior to the administration in II in the rapidity of negativization of blood cultures in patients with bacteremia. 3)Security Objectives: 3.1)PENDIENTE DE TRADUCIR ;Primary end point(s): Number of responding patients. Responder is defined as a patient with defervescence (axillary temperature <37.5ºC, for 24 hours and documented in a minimum of 3 determinations, without reappearance of fever) during the first 5 days of treatment with ABL and without a modification of the antibiotic treatment.

—

Secondary

Measure	Time frame
Timepoint(s) of evaluation of this end point: During the 5 days of treatment with ABL, and without modification of the antibiotic treatment.; Secondary end point(s): 1) Clinical variables: 1.1)Time (hours) until the defervescence, without a modification the antibiotic treatment. 1.2)Number of patients that do not change the ABL treatment during the 5 days of study. 1.3)Number of patients in which the PK / PD goal is reached, defined as antibiotic concentration time above a MIC of 50% (50% ft> MIC), 75% (75% ft> MIC) and 100% (100% ft> MIC) of the administration interval. In cases where there is a microbiological documentation, the determined MIC will be selected. Otherwise, the highest susceptible MIC for all likely organisms according to EUCAST2 will be selected (for P. aeruginosa: 16mg/L for piperacillin-tazobactam, 8mg/L for cefepime and 2mg/L for meropenem). 1.4)Number of occasions per patient in which the PK / PD goal is reached, defined as antibiotic concentration time above a MIC of 50% (50% ft> MIC), 75% (75% ft> MIC) and 100% (100% ft> MIC) of the administration interval. In cases where there is a microbiological documentation, the determined MIC will be selected. Otherwise, the highest susceptible MIC for all likely organisms according to EUCAST2 will be selected (for P. aeruginosa: 16mg/L for piperacillin-tazobactam, 8mg/L for cefepime and 2mg/L for meropenem). 1.5)Number of patients with clinical resolution of the infectious disease within 5 days and 30 days. 1.6) Number of patients who normalize (<5 mg / dL C-reactive protein, (CRP); <0.1 mcg/dL procalcitonin) or decrease (50% of the maximum value) CRP and procalcitonin within the first 5 days of treatment. 1.7) Time (days) until normalization / decrease of 50% of CRP. 1.8) All-cause crude mortality at 30 days. 1.9) A population pharma	—

Measure

Time frame

Timepoint(s) of evaluation of this end point: During the 5 days of treatment with ABL, and without modification of the antibiotic treatment.; Secondary end point(s): 1) Clinical variables: 1.1)Time (hours) until the defervescence, without a modification the antibiotic treatment. 1.2)Number of patients that do not change the ABL treatment during the 5 days of study. 1.3)Number of patients in which the PK / PD goal is reached, defined as antibiotic concentration time above a MIC of 50% (50% ft> MIC), 75% (75% ft> MIC) and 100% (100% ft> MIC) of the administration interval. In cases where there is a microbiological documentation, the determined MIC will be selected. Otherwise, the highest susceptible MIC for all likely organisms according to EUCAST2 will be selected (for P. aeruginosa: 16mg/L for piperacillin-tazobactam, 8mg/L for cefepime and 2mg/L for meropenem). 1.4)Number of occasions per patient in which the PK / PD goal is reached, defined as antibiotic concentration time above a MIC of 50% (50% ft> MIC), 75% (75% ft> MIC) and 100% (100% ft> MIC) of the administration interval. In cases where there is a microbiological documentation, the determined MIC will be selected. Otherwise, the highest susceptible MIC for all likely organisms according to EUCAST2 will be selected (for P. aeruginosa: 16mg/L for piperacillin-tazobactam, 8mg/L for cefepime and 2mg/L for meropenem). 1.5)Number of patients with clinical resolution of the infectious disease within 5 days and 30 days. 1.6) Number of patients who normalize (<5 mg / dL C-reactive protein, (CRP); <0.1 mcg/dL procalcitonin) or decrease (50% of the maximum value) CRP and procalcitonin within the first 5 days of treatment. 1.7) Time (days) until normalization / decrease of 50% of CRP. 1.8) All-cause crude mortality at 30 days. 1.9) A population pharma

—

Countries

Spain

Contacts

Public ContactDra. Júlia Laporte Amargós

Dra. Júlia Laporte Amargós. Servicio de Enfermedades Infecciosas. Hospital Universitari de Bellvitge

julia_laporte@hotmail.com34932607625

Outcome results

None listed