Febrile NeutropeniaPhase 4BEATLENCT04233996
Efficacy of Extended Infusion of β-lactam Antibiotics for the Treatment of Febrile Neutropenia in Hematologic Patients
A Phase 4 study testing Piperacillin-Tazobactam 4 g-0.5 g, Cefepime 2000 mg and Meropenem 1000 mg in people with Febrile Neutropenia, run by Hospital Universitari de Bellvitge at 1 site in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Febrile Neutropenia
- What is being tested?
- Piperacillin-Tazobactam 4 g-0.5 g, Cefepime 2000 mg and Meropenem 1000 mg
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 150 participants
- Where
- 1 siteSpain
- Study dates
- 5 Jun 2019to 31 Dec 2022
- Phase
- Phase 4
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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.
Trial locations and contacts
1 site in 1 country.
Julia Laporte-Amargos, MD contact
Spain1 site, 1 recruiting
- Recruiting
Hospital Duran i Reynals
L'Hospitalet de Llobregat, Barcelona, 08908
Carlota Gudiol, PhD
About this study
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)
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.
Read the 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.
- Conditions
- Febrile Neutropenia
- Being tested
- Piperacillin-Tazobactam 4 g-0.5 g, Cefepime 2000 mg, Meropenem 1000 mg
- Keywords
- Febrile neutropenia, Beta-lactam antibiotics, Cefepime, Meropenem, Piperacillin-tazobactam, Extended infusion
- Medical subject headings
- Febrile Neutropenia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Piperacillin-Tazobactam 4 g-0.5 gDrug
Patients with FN who empirical treatment with piperacillin-tazobactam 4g/6h
Cefepime 2000 mgDrug
Patients with FN who required empirical treatment with cefepime 2g/8h
Meropenem 1000 mgDrug
Patients with FN who required empirical treatment with meropenem 1g/8h
| Study group | Role | What they receive |
|---|---|---|
| Extended infusion | Experimental | Piperacillin-tazobactam, cefepime or meropenem will be administered in half time of the dosing interval Receives: Drug: Piperacillin-Tazobactam 4 g-0.5 g; Drug: Cefepime 2000 mg; Drug: Meropenem 1000 mg |
| Intermittent infusion | Active comparator | Piperacillin-tazobactam, cefepime or meropenem will be administered in 30 minutes Receives: Drug: Piperacillin-Tazobactam 4 g-0.5 g; Drug: Cefepime 2000 mg; Drug: Meropenem 1000 mg |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical efficacy of extended infusion: Number of patients with defervescence
Number of patients with defervescence (<37.5 ºC, for 24 hours) without modifying the antibiotic treatment
Measured: 5 days
Secondary outcomes (14)
Pharmacokinetic target
Number of patients in whom the free antibiotic concentration remains above the MIC of the suspected or isolated microorganism, for 50%, 75% and 100% of the dosing interval.
Measured: 5 days
Inflammatory biomarker
Number of patients who normalize or decrease in more than 50% of the peak value of the C-reactive protein.
Measured: 5 days
Overall mortality at 30 days
Number of patients who died for any reason
Measured: 30 days
Bacteraemia clearance
Time in days until bacteraemia clearance.
Measured: 30 days
Adverse events
Incidence of adverse events in both groups
Measured: 30 days
Pharmacokinetic analysis and population pharmacokinetics of meropenem, piperacillin and cefepime in neutropenic patients: Volume of distribution
Population mean value of volume of distribution of antibiotics during critical illness. Mean population volume of distribution will be derived from pooled data of antibiotic concentrations. Covariates of influence on volume of distribution will be incorporated within a population pharmacokinetic model.
Measured: 5 days
Pharmacokinetic analysis and population pharmacokinetics of meropenem, piperacillin and cefepime in neutropenic patients: Clearance
Population mean value of clearance of antibiotics during critical illness. Mean population clearance will be derived from pooled data of antibiotic concentrations. Covariates of influence on drug clearance will be incorporated within a population pharmacokinetic model
Measured: 5 days
Covariables analysis: biometric values: weight
Assessment of the impact of patient's weight [in kg]
Measured: 5 days
Covariables analysis: biometric values: age
Assessment of the impact of patient's age [in years]
Measured: 5 days
Covariables analysis: biochemical data: serum albumin
Assessment of the impact of total serum albumin [in g/L]
Measured: 5 days
Covariables analysis: biochemical data: blood urea
Assessment of the impact of the urea [in mmol/L]
Measured: 5 days
Covariables analysis: biochemical data: blood creatinine
Assessment of the impact of the creatinine [in umol/L]
Measured: 5 days
Covariables analysis: clinical data: 24h diuresis
Assessment of the impact of 24h diuresis [in mL/day]
Measured: 5 days
Pharmacokinetic analysis and population pharmacokinetics: time above a critical concentration value for plasma concentrations
Analysis of the antibiotic pharmacokinetic profiles by means of appropriate software to calculate the actual mean and median values of the fraction of the time between two successive drug administrations during which plasma concentrations of meropenem, piperacillin and cefepime remain above a critical value ("S" breakpoint of the corresponding antibiotic [meropenem, piperacillin and cefepime: European Committee for Antimicrobials Susceptibility Testing [EUCAST] value) in the study population, and to determine its value in a simulated population (Monte Carlo simulations; 1000 simulated patients).
Measured: 5 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jan 2020
- Study start5 Jun 2019
- Primary completion30 Dec 2021 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Febrile NeutropeniaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 150 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Hospital Universitari de Bellvitge
- Sponsor type
- University, hospital or other
- Collaborators
- Institut d'Investigació Biomèdica de Bellvitge, Instituto de Salud Carlos III
- Responsible party
- Principal investigator, Carlota Gudiol, Hospital Universitari de Bellvitge
- Investigators
- Carlota Gudiol, PhD, Principal investigator, Hospital Universitari de Bellvitge
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04233996
- Sponsor's protocol ID
- 2018-001476-37
- Other IDs
- 2018
- Acronym
- BEATLE
- Status last verified
- Feb 2021
- First submitted
- 4 Sep 2019
- Last updated
- 12 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
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.
PubMed 32423462
Study at a glance
From the registry record, last updated by the sponsor on 12 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT04233996
- Acronym / sponsor ID
- BEATLE / 2018-001476-37
- Conditions
- Febrile Neutropenia
- Keywords
- Febrile neutropenia, Beta-lactam antibiotics, Cefepime, Meropenem, Piperacillin-tazobactam, Extended infusion
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 150 participants (estimated)
- Lead sponsor
- Hospital Universitari de BellvitgeUniversity, hospital or other
- Collaborators
- Institut d'Investigació Biomèdica de Bellvitge, Instituto de Salud Carlos III
- Study start
- 5 Jun 2019 (actual)
- Primary completion
- 30 Dec 2021 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 21 Jan 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Extended infusion | Experimental | Drug: Piperacillin-Tazobactam 4 g-0.5 g, Drug: Cefepime 2000 mg, Drug: Meropenem 1000 mgPiperacillin-tazobactam, cefepime or meropenem will be administered in half time of the dosing interval |
| Intermittent infusion | Active comparator | Drug: Piperacillin-Tazobactam 4 g-0.5 g, Drug: Cefepime 2000 mg, Drug: Meropenem 1000 mgPiperacillin-tazobactam, cefepime or meropenem will be administered in 30 minutes |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Adult patients (age ≥18 years) of both sexes.
- Patients admitted in Hematological wards.
- With any of the following diagnoses:
- 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.
Key exclusion criteria (7 listed)
- 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)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Piperacillin-Tazobactam 4 g-0.5 gPatients with FN who empirical treatment with piperacillin-tazobactam 4g/6h | Drug | Extended infusion, Intermittent infusion |
| Cefepime 2000 mgPatients with FN who required empirical treatment with cefepime 2g/8h | Drug | Extended infusion, Intermittent infusion |
| Meropenem 1000 mgPatients with FN who required empirical treatment with meropenem 1g/8h | Drug | Extended infusion, Intermittent infusion |
Primary outcome
Clinical efficacy of extended infusion: Number of patients with defervescence
Time frame: 5 days
Number of patients with defervescence (<37.5 ºC, for 24 hours) without modifying the antibiotic treatment
14 secondary outcomes
Pharmacokinetic target
Time frame: 5 days
Inflammatory biomarker
Time frame: 5 days
Overall mortality at 30 days
Time frame: 30 days
Bacteraemia clearance
Time frame: 30 days
Adverse events
Time frame: 30 days
Pharmacokinetic analysis and population pharmacokinetics of meropenem, piperacillin and cefepime in neutropenic patients: Volume of distribution
Time frame: 5 days
Pharmacokinetic analysis and population pharmacokinetics of meropenem, piperacillin and cefepime in neutropenic patients: Clearance
Time frame: 5 days
Covariables analysis: biometric values: weight
Time frame: 5 days
Covariables analysis: biometric values: age
Time frame: 5 days
Covariables analysis: biochemical data: serum albumin
Time frame: 5 days
Covariables analysis: biochemical data: blood urea
Time frame: 5 days
Covariables analysis: biochemical data: blood creatinine
Time frame: 5 days
Covariables analysis: clinical data: 24h diuresis
Time frame: 5 days
Pharmacokinetic analysis and population pharmacokinetics: time above a critical concentration value for plasma concentrations
Time frame: 5 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Feb 2021.
- Derived from this study: PubMed 32423462Laporte-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.
- Spanish clinical trial registration (REEC, registro español de estudios clínicos)Link provided by the sponsor.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Julia Laporte-Amargos, MD contact
Carlota Gudiol, PhD principal investigator
Hospital Universitari de Bellvitge
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Piperacillin-Tazobactam 4 g-0.5 g, Cefepime 2000 mg and Meropenem 1000 mg in people with Febrile Neutropenia, run by Hospital Universitari de Bellvitge at 1 site in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Carlota Gudiol, PhD (0034675786820, carlotagudiol@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical efficacy of extended infusion: Number of patients with defervescence (time frame: 5 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04233996, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Feb 2021.