Clinical trial NCT05926063: Stopping Antibiotics After 3 Days for the Treatment of High-risk FEbrile Neutropenia
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
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE4
Conditions: Neutropenia, Febrile
Keywords: Neutropenia
Leukemia
Stem Cell Transplant Complications
Infections
Lead sponsor: Universitaire Ziekenhuizen KU Leuven
Sponsor class: OTHER
Collaborators: name: University Hospital, Ghent
name: Universitair Ziekenhuis Brussel
name: University Hospital, Antwerp
name: AZ Sint-Jan AV
name: Centre Hospitalier Universitaire de Liege
name: Cliniques universitaires Saint-Luc- Université Catholique de Louvain
First posted: 2023-07-03
Enrollment: 410
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Comparison of two treatment strategies
Primary purpose: SUPPORTIVE_CARE

Brief 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.


Eligibility criteria: 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.

Primary outcomes:
measure: 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.
timeFrame: 42 days
Secondary outcomes:
measure: Incidence of bacteraemia within 42 days after randomisation
timeFrame: 42 days
measure: Clinically documented infections
timeFrame: 42 days
measure: Number of documented bacterial infections
timeFrame: 42 days
measure: Total days of non-prophylactic antibiotics given to the patient at engraftment
timeFrame: 42 days
measure: Total numbers of antibiotic switches before neutrophil recovery
timeFrame: 42 days
measure: Incidence of Clostridium difficile infection
timeFrame: 42 days
measure: Incidence, severity and duration of diarrhea
timeFrame: 42 days
measure: Incidence of candidemia
timeFrame: 42 days
measure: Length of hospital stay in the first 42 days after randomization
timeFrame: 42 days
measure: Number of patients admitted to the ICU within 42 days after randomisation
timeFrame: 42 days
measure: Number of readmissions within 42 days
timeFrame: 42 days
measure: Number of patients with a culture (surveillance or diagnostic culture) positive for resistant bacteria: VRE; ESBL; MRSA; and/or CPE
timeFrame: 42 days
measure: Duration of hospitalization
timeFrame: 42 days
measure: Number of patients in the short treatment arm with ongoing fever at time of EBAT stop
timeFrame: 42 days
measure: Incidence of acute GVHD (grade II or higher) in the transplanted study population
timeFrame: 42 days
Other outcomes:
Locations:
city: Leuven
country: Belgium
facility: University Hospitals Leuven
state: Vlaams-Brabant
Study officials:
affiliation: Universitaire Ziekenhuizen KU Leuven
name: Johan Maertens, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: