Stopping Antibiotics After 3 Days for the Treatment of High-risk FEbrile Neutropenia

Neutropenia, Febrile Clinical Trial

— SAFE  

Official title:

Stopping Antibiotics After 3 Days for the Treatment of FEbrile Neutropenia in Haematology Patients (SAFE Study): a Randomized Open-label Non-inferiority Trial

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05926063
• Other study ID #: S66527
• Secondary ID: 2022-500389-84
• Status: Recruiting
• Phase: Phase 4
• Start date: February 26, 2024
• Est. completion date: July 2026

Study information

• Verified date: June 2023
• Source: Universitaire Ziekenhuizen KU Leuven
• Contact: Robina Aerts, MD
• Phone: +32 16 34 48 77
• Email: robina.aerts[@]kuleuven.be
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The goal of this clinical trial is to compare a short course of antibiotics in patients in whom no bacterial infection is found with the current "golden standard": long-term antibiotic treatment in adult hematology patients who develop neutropenic fever. The main question it aims to answer is: whether the short-term treatment is equally safe for patients, hence the name 'SAFE study'. Participants will be randomly assigned (randomized) to one of two treatment options once they develop neutropenic fever: short-term or long-term antibiotic treatment. An additional blood sample, urine sample and stool sample will be collected. Researchers will compare the short-term and the long-term antibiotic treatment groups to see if the short treatment is equally safe as the long-term treatment group.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 410
• Est. completion date: July 2026
• Est. primary completion date: July 2026
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

Inclusion Criteria:

• Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures;
• Age older than 16 years;
• Intensive therapy is started within three days before randomization for one of the

following haematological conditions:

• Remission induction chemotherapy for newly diagnosed acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS); OR
• Re-induction chemotherapy for relapsed after haematological remission lasting for a minimum duration of 6 months; OR
• Conditioning regimen to prepare for an allogeneic HCT; OR
• Conditioning regimen to prepare for an autologous HCT.
• Expected longstanding (= 7 days) neutropenia (ANC < 0.5x10^9/L);
• Expected length of hospital stay of at least 10 days.

Exclusion Criteria:

1. Clinically or microbiologically documented infection;

2. Patient already receives broad spectrum antibiotic therapy;

3. Any critical illness for which Intensive Care Unit treatment is required;

4. SOFA score = 11;

5. Longstanding neutropenia (>21 days) prior inclusion;

6. Previous enrolment in this study;

7. Not able to provide written informed consent;

8. Any disorder, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol;

9. Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Trial.

Related Conditions & MeSH terms

• Febrile Neutropenia
• Fever
• Hyperthermia
• Neutropenia
• Neutropenia, Febrile

Intervention

Other:
• Comparison short vs extended EBAT treatment group
This study compares two management strategies of patients undergoing treatment with chemotherapy or a stem cell transplantation. One strategy is to treat these patients at the time of febrile neutropenia with a fixed 72 hours course of EBAT. The other, more commonly followed strategy is a longer minimum EBAT duration of 5 days as well as other variables like neutrophil recovery and defervescence. In both arms, definitive treatment is given when an infectious cause of the fever is found according to local guidelines (e.g. pneumonia or mucosits with bacteremia).

Locations

Country	Name	City	State
Belgium	University Hospitals Leuven	Leuven	Vlaams-Brabant

Sponsors (7)

Lead Sponsor	Collaborator
Universitaire Ziekenhuizen KU Leuven	AZ Sint-Jan AV, Centre Hospitalier Universitaire de Liege, Cliniques universitaires Saint-Luc- Université Catholique de Louvain, Universitair Ziekenhuis Brussel, University Hospital, Antwerp, University Hospital, Ghent

Country where clinical trial is conducted

Belgium, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Absence of a serious medical complication (SMC) following 42 days after randomisation. SMC is defined as: Death; and/or ICU admission; and/or Septic shock requiring vasopressive therapy.		42 days
Secondary	Incidence of bacteraemia within 42 days after randomisation		42 days
Secondary	Clinically documented infections		42 days
Secondary	Number of documented bacterial infections		42 days
Secondary	Total days of non-prophylactic antibiotics given to the patient at engraftment		42 days
Secondary	Total numbers of antibiotic switches before neutrophil recovery		42 days
Secondary	Incidence of Clostridium difficile infection		42 days
Secondary	Incidence, severity and duration of diarrhea		42 days
Secondary	Incidence of candidemia		42 days
Secondary	Length of hospital stay in the first 42 days after randomization		42 days
Secondary	Number of patients admitted to the ICU within 42 days after randomisation		42 days
Secondary	Number of readmissions within 42 days		42 days
Secondary	Number of patients with a culture (surveillance or diagnostic culture) positive for resistant bacteria: VRE; ESBL; MRSA; and/or CPE		42 days
Secondary	Duration of hospitalization		42 days
Secondary	Number of patients in the short treatment arm with ongoing fever at time of EBAT stop		42 days
Secondary	Incidence of acute GVHD (grade II or higher) in the transplanted study population		42 days