Efficacy of Extended Infusion of β-lactam Antibiotics for the Treatment of Febrile Neutropenia in Hematologic Patients (BEATLE)

Catalan Institute of Health

Status and phase: Unknown; Phase 4

Conditions: Febrile Neutropenia

Treatments: Drug: Cefepime 2000 mg; Drug: Meropenem 1000 mg; Drug: Piperacillin-Tazobactam 4 g-0.5 g

Study type: Interventional

Funder types: Other

Identifiers

NCT04233996

2018-001476-37

Details and patient eligibility

About

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.

Full 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.

Enrollment: 150 estimated patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

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.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

---

150 participants in 2 patient groups

Extended infusion

Experimental group

Description:

Piperacillin-tazobactam, cefepime or meropenem will be administered in half time of the dosing interval

Treatment:

Drug: Cefepime 2000 mg

Drug: Meropenem 1000 mg

Drug: Piperacillin-Tazobactam 4 g-0.5 g

Intermittent infusion

Active Comparator group

Description:

Piperacillin-tazobactam, cefepime or meropenem will be administered in 30 minutes

Treatment:

Drug: Cefepime 2000 mg

Drug: Meropenem 1000 mg

Drug: Piperacillin-Tazobactam 4 g-0.5 g