Short-term Antibiotic Treatment for Unexplained Fever in Solid Cancer Patients With Febrile Neutropenia

Study Overview
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Brief Summary
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The purpose of this study is to determine whether short-course antibiotic therapy is safe and effective for the treatment of cancer patients with febrile neutropenia.

Detailed Description
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Febrile neutropenia remains a major cause of morbidity in solid cancer patients. There is an unresolved question regarding the appropriate duration of antibiotic treatment for patients with febrile neutropenia of unknown origin. Current guidelines recommend at least seven days of antibiotic treatment. Several studies have demonstrated the safety of early antibiotic discontinuation in patients with febrile neutropenia. We plan an open label randomized controlled trial to compare early antibiotic discontinuation to the accepted prolonged antibiotic treatment protocol

Official Title
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Short-term Antibiotic Treatment for Unexplained Fever in Solid Cancer Patients With Febrile Neutropenia: Randomized-controlled Trial

Conditions
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Febrile Neutropenia

Intervention / Treatment
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* Other: Early antibiotic discontinuation
* Other: Usual practice


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adults >18 years providing signed informed consent Patients with solid tumors, lymphoma, multiple myeloma or chronic lymphocytic leukemia, regardless of disease status or previous chemotherapy Documented febrile neutropenia No clinically or microbiologically documented infection after 72 hours Exclusion Criteria: Previous enrollment in this study Concurrent participation in another interventional trial Severe sepsis or septic shock Acute leukemia, autologous or allogeneic hematopoietic stem-cell transplantation Diarrhea suspected by treating physician to be Irinotecan induced Any antibiotic treatment for >48h in the last week before enrollment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Early antibiotic discontinuation<br>Antibiotic treatment stopped after 72h, regardless of fever.The antibiotics used will be piperacillin tazobactam for high-risk patients and amoxycillin-clavulanate + ciprlofloxacin for low-risk patients (defined by MASCC scoring system). Alternatives in case of penicillin allergy will be ceftazidine and levofloxacin, respectively. | Other: Early antibiotic discontinuation<br>* Antibiotic treatment for unexplained febrile neutropenia stopped after 72 hours, regardless of fever<br>|
| Other: Usual practice<br>Antibiotic treatment continued according to accepted guidelines and current clinical practice. The antibiotics used will be piperacillin tazobactam for high-risk patients and amoxycillin-clavulanate + ciprlofloxacin for low-risk patients (defined by MASCC scoring system). Alternatives in case of penicillin allergy will be ceftazidine and levofloxacin, respectively. | Other: Usual practice<br>* Continued antibiotic treatment as accepted by guidelines for febrile neutropenia<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Composite outcome of all-cause mortality, severe infection, severe diarrhea or fever | Composite outcome of all-cause mortality, severe infection (defined as clinically or microbiologically documented infection with systemic inflammatory response syndrome (SIRS)), severe diarrhea (>=3 daily for >=2 days) or fever (>38) | After day 7 from randomization until day 30 | 
| Total febrile or antibiotic days | Total febrile or antibiotic days from the day of randomization until day 30, defined as a day with one or more temperature measurement >38.0°C or a day on which antibiotic treatment was prescribed for any reason other than prophylaxis | From the day of randomization until day 30 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinically and/or microbiologically documented infections | Clinically and/or microbiologically documented infections within 30 days of randomization. We will use the 2008 CDC/NHSN surveillance definitions of health-care associated infections for bacterial infections (including Clostridium difficile) and the 2008 revised definitions for invasive fungal infections. | 30 days | 
| Total in-hospital days | Total in-hospital days from the day of randomization up to day 30 | 30 days | 
| Re-admission | Rates of re-admission for any reason other than planned chemotherapy. | 30 days | 
| Antibiotic treatment | Patients receiving antibiotic treatment after day 7 from randomization until day 30 | After day 7 from randomization until day 30 | 
| Antifungal treatment | Institution of antifungal treatment | 30 days | 
| Duration of intravenous antibiotic treatment | Duration of intravenous antibiotic treatment | 30 days | 
| Duration of neutropenia | Duration of neutropenia | 30 days | 
| Development of resistance | Development of resistance, defined as clinical isolates resistant to antibiotics previously used in the febrile episode. Surveillance sampling will not be conducted. | 30 days | 
| All-cause mortality | All-cause mortality | 30 days | 
| Infection-related mortality | Cause of death adjudicated by the trial's safety committee | 30 days after randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Febrile neutropenia, Unexplained fever, Duration, Short-term antibiotic treatment