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

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

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.

Study Overview

• Status: Withdrawn
• Conditions: Febrile Neutropenia
• Intervention / Treatment: Other: Early antibiotic discontinuation; Other: Usual practice

Detailed Description

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

• Study Type: Interventional
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Israel
  • Petah Tikvah, Israel
    • Rabin Medical Center, Beilinson Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Early antibiotic discontinuation; 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; Antibiotic treatment for unexplained febrile neutropenia stopped after 72 hours, regardless of fever
Other: Usual practice; 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; Continued antibiotic treatment as accepted by guidelines for febrile neutropenia

What is the study measuring?

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
All-cause mortality	All-cause mortality	30 days
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
Infection-related mortality	Cause of death adjudicated by the trial's safety committee	30 days after randomization

Collaborators and Investigators

• Sponsor: Rabin Medical Center
• Investigators: Principal Investigator: Dafna Yahav, MD, Rabin Medical Center; Principal Investigator: Mical Paul, MD, Rabin Medical Center; Principal Investigator: Leonard Leibovici, Prof, Rabin Medical Center

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Anticipated): January 1, 2014
• Study Completion (Anticipated): January 1, 2015

Study Registration Dates

• First Submitted: September 17, 2011
• First Submitted That Met QC Criteria: October 9, 2011
• First Posted (Estimate): October 12, 2011

Study Record Updates

• Last Update Posted (Estimate): June 7, 2013
• Last Update Submitted That Met QC Criteria: June 6, 2013
• Last Verified: June 1, 2013

More Information

Terms related to this study

• Keywords: Febrile neutropenia; Duration; Unexplained fever; Short-term antibiotic treatment
• Additional Relevant MeSH Terms: Wounds and Injuries; Hematologic Diseases; Agranulocytosis; Leukopenia; Leukocyte Disorders; Body Temperature Changes; Heat Stress Disorders; Neutropenia; Hyperthermia; Fever; Febrile Neutropenia; Anti-Infective Agents; Anti-Bacterial Agents
• Other Study ID Numbers: RabinMC6249