Neutropenia, FebrilePhase 4SAFENCT05926063
Stopping Antibiotics After 3 Days for the Treatment of High-risk FEbrile Neutropenia
A Phase 4 study testing Comparison short vs extended EBAT treatment group in people with Neutropenia, Febrile, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Neutropenia, Febrile
- What is being tested?
- Comparison short vs extended EBAT treatment group
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 450 participants
- Where
- 1 siteBelgium
- Study dates
- 26 Feb 2024to 14 May 2026
- Phase
- Phase 4
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
- 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
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- 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.
Who cannot join
- Clinically or microbiologically documented infection;
- Patient already receives broad spectrum antibiotic therapy;
- Any critical illness for which Intensive Care Unit treatment is required;
- SOFA score ≥ 11;
- Longstanding neutropenia (>21 days) prior inclusion;
- Previous enrolment in this study;
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- Not able to provide written informed consent;
- Any disorder, which in the Investigator's opinion might jeopardise the participant's safety or compliance with the protocol;
- Any prior or concomitant treatment(s) that might jeopardise the participant's safety or that would compromise the integrity of the Trial.
Trial locations and contacts
1 site in 1 country.
About this study
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
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'.
Read more
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.
- Conditions
- Neutropenia, Febrile
- Being tested
- Comparison short vs extended EBAT treatment group
- Keywords
- Neutropenia, Leukemia, Stem Cell Transplant Complications, Infections
- Medical subject headings
- Febrile Neutropenia, Neutropenia, Leukemia, Infections
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Comparison short vs extended EBAT treatment groupOther
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).
| Study group | Role | What they receive |
|---|---|---|
| Short treatment group | Experimental | Empirical broad-spectrum antibiotics (EBAT) as per local protocol:
* Meropenem 3 x 1(/2) g IV; OR
* Piperacilline-Tazobactam 4 x 4 g IV; OR
* Cefepime 3 x 2 g IV; OR
* Ceftazidim 3 x 2 g IV
Short treatment group: EBAT will be discontinued:
* After 3x24 hours;
* Irrespective of presence of fever; AND
* If no clinical of microbiological infection is documented. Receives: Other: Comparison short vs extended EBAT treatment group |
| Extended treatment group | Active comparator | Empirical broad-spectrum antibiotics (EBAT) as per local protocol:
* Meropenem 3 x 1(/2) g IV; OR
* Piperacilline-Tazobactam 4 x 4 g IV; OR
* Cefepime 3 x 2 g IV; OR
* Ceftazidim 3 x 2 g IV
Extended treatment arm: EBAT will be continued:
* At least 5x24 hours;
* Until afebrile (TMT<38.0°C) for at least 48h; OR
* Until resolution of neutropenia (ANC >0,5 x109/L); OR
* Until they have been treated 10 days, whatever comes first. Receives: Other: Comparison short vs extended EBAT treatment group |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 42 days
Secondary outcomes (15)
Incidence of bacteraemia within 42 days after randomisation
Measured: 42 days
Clinically documented infections
Measured: 42 days
Number of documented bacterial infections
Measured: 42 days
Total days of non-prophylactic antibiotics given to the patient at engraftment
Measured: 42 days
Total numbers of antibiotic switches before neutrophil recovery
Measured: 42 days
Incidence of Clostridium difficile infection
Measured: 42 days
Incidence, severity and duration of diarrhea
Measured: 42 days
Incidence of candidemia
Measured: 42 days
Length of hospital stay in the first 42 days after randomization
Measured: 42 days
Number of patients admitted to the ICU within 42 days after randomisation
Measured: 42 days
Number of readmissions within 42 days
Measured: 42 days
Number of patients with a culture (surveillance or diagnostic culture) positive for resistant bacteria: VRE; ESBL; MRSA; and/or CPE
Measured: 42 days
Duration of hospitalization
Measured: 42 days
Number of patients in the short treatment arm with ongoing fever at time of EBAT stop
Measured: 42 days
Incidence of acute GVHD (grade II or higher) in the transplanted study population
Measured: 42 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 Jul 2023
- Study start26 Feb 2024
- Primary completion8 Mar 2026
- Study completion14 May 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Neutropenia, FebrileStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- 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
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Comparison of two treatment strategies: short versus extended course of beta-lactam antibiotics
- Masking
- None (open label)
- Enrolment
- 450 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- University Hospital, Ghent, Universitair Ziekenhuis Brussel, University Hospital, Antwerp, AZ Sint-Jan AV, Centre Hospitalier Universitaire de Liege, Cliniques universitaires Saint-Luc- Université Catholique de Louvain, Jules Bordet Institute, Grand Hôpital de Charleroi
- Responsible party
- Sponsor
- Investigators
- Johan Maertens, MD, PhD, Principal investigator, Universitaire Ziekenhuizen KU LeuvenYuri Charles Vanbiervliet, MD, Principal investigator, Universitaire Ziekenhuizen KU Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05926063
- Sponsor's protocol ID
- S66527
- Other IDs
- 2022-500389-84
- Acronym
- SAFE
- Status last verified
- May 2026
- First submitted
- 21 Jun 2023
- Last updated
- 23 Oct 2026
- Results posted
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No