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)
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 150
- 试验地点
- 1
- 主要终点
- Clinical efficacy of extended infusion: Number of patients with defervescence
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adult patients (age ≥18 years) of both sexes.
- •Patients admitted in Hematological wards.
- •With any of the following diagnoses:
- •Acute leukemia receiving chemotherapy.
- •Autologous or allogeneic hematopoietic stem cell transplant recipients.
- •With an episode of febrile neutropenia: ≥ 38.0ºC and <500 neutrophils/mm3 or <1000 with a predicted decrease within 24-48 hours.
- •Patient requiring treatment with a beta-lactam antibiotic: cefepime, piperacillin /tazobactam or meropenem, in monotherapy or in combination with another antibiotic.
- •Written informed consent has been obtained from the patient or their legal representative grants.
排除标准
- •Allergy to study drugs.
- •Patient receiving systemic antibiotic treatment (except for prophylaxis) at the time of onset of febrile neutropenia.
- •Absence of fever.
- •Patients with epilepsy.
- •Severe renal impairment (defined as creatinine clearance <30 mL / min)
- •Previously enrolled patients in whom the time between the inclusion and the current episode is less than 5 weeks.
- •Previously enrolled patients without current resolution of the first episode.
研究组 & 干预措施
Extended infusion
Piperacillin-tazobactam, cefepime or meropenem will be administered in half time of the dosing interval
干预措施: Piperacillin-Tazobactam 4 g-0.5 g (Drug)
Extended infusion
Piperacillin-tazobactam, cefepime or meropenem will be administered in half time of the dosing interval
干预措施: Cefepime 2000 mg (Drug)
Extended infusion
Piperacillin-tazobactam, cefepime or meropenem will be administered in half time of the dosing interval
干预措施: Meropenem 1000 mg (Drug)
Intermittent infusion
Piperacillin-tazobactam, cefepime or meropenem will be administered in 30 minutes
干预措施: Piperacillin-Tazobactam 4 g-0.5 g (Drug)
Intermittent infusion
Piperacillin-tazobactam, cefepime or meropenem will be administered in 30 minutes
干预措施: Cefepime 2000 mg (Drug)
Intermittent infusion
Piperacillin-tazobactam, cefepime or meropenem will be administered in 30 minutes
干预措施: Meropenem 1000 mg (Drug)
结局指标
主要结局
Clinical efficacy of extended infusion: Number of patients with defervescence
时间窗: 5 days
Number of patients with defervescence (\<37.5 ºC, for 24 hours) without modifying the antibiotic treatment
次要结局
- Pharmacokinetic target(5 days)
- Inflammatory biomarker(5 days)
- Overall mortality at 30 days(30 days)
- Bacteraemia clearance(30 days)
- Adverse events(30 days)
- Pharmacokinetic analysis and population pharmacokinetics of meropenem, piperacillin and cefepime in neutropenic patients: Volume of distribution(5 days)
- Pharmacokinetic analysis and population pharmacokinetics of meropenem, piperacillin and cefepime in neutropenic patients: Clearance(5 days)
- Covariables analysis: biometric values: weight(5 days)
- Covariables analysis: biometric values: age(5 days)
- Covariables analysis: biochemical data: serum albumin(5 days)
- Covariables analysis: biochemical data: blood urea(5 days)
- Covariables analysis: biochemical data: blood creatinine(5 days)
- Covariables analysis: clinical data: 24h diuresis(5 days)
- Pharmacokinetic analysis and population pharmacokinetics: time above a critical concentration value for plasma concentrations(5 days)
研究者
Carlota Gudiol
Principal Investigator
Hospital Universitari de Bellvitge