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

Sponsor

Universitaire Ziekenhuizen KU Leuven (Other)

Overall Status

Not yet recruiting

CT.gov ID

NCT05926063

Collaborator

University Hospital, Ghent (Other), Universitair Ziekenhuis Brussel (Other), University Hospital, Antwerp (Other), AZ Sint-Jan AV (Other), Centre Hospitalier Universitaire de Liege (Other), Cliniques universitaires Saint-Luc- Université Catholique de Louvain (Other)

410

Enrollment

Arms

Anticipated Duration (Months)

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Neutropenia, Febrile	Other: Comparison short vs extended EBAT treatment group	Phase 4

Study Design

Study Type:

Interventional

Anticipated Enrollment :

410 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Supportive Care

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

Anticipated Study Start Date :

Jul 1, 2023

Anticipated Primary Completion Date :

Jul 1, 2026

Anticipated Study Completion Date :

Jul 1, 2026

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Short treatment group 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.	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).
Active Comparator: Extended treatment group 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 5 consecutive days; OR Until resolution of neutropenia (ANC >0,5 x109/L); OR Until they have been treated 10 days, whatever comes first.	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).

Arm

Intervention/Treatment

Experimental: Short treatment group

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.

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).

Active Comparator: Extended treatment group

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 5 consecutive days; OR Until resolution of neutropenia (ANC >0,5 x109/L); OR Until they have been treated 10 days, whatever comes first.

Other: Comparison short vs extended EBAT treatment group

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

Incidence of bacteraemia within 42 days after randomisation [42 days]
Clinically documented infections [42 days]
Number of documented bacterial infections [42 days]
Total days of non-prophylactic antibiotics given to the patient at engraftment [42 days]
Total numbers of antibiotic switches before neutrophil recovery [42 days]
Incidence of Clostridium difficile infection [42 days]
Incidence, severity and duration of diarrhea [42 days]
Incidence of candidemia [42 days]
Length of hospital stay in the first 42 days after randomization [42 days]
Number of patients admitted to the ICU within 42 days after randomisation [42 days]
Number of readmissions within 42 days [42 days]
Number of patients with a culture (surveillance or diagnostic culture) positive for resistant bacteria: VRE; ESBL; MRSA; and/or CPE [42 days]
Duration of hospitalization [42 days]
Number of patients in the short treatment arm with ongoing fever at time of EBAT stop [42 days]
Incidence of acute GVHD (grade II or higher) in the transplanted study population [42 days]

Eligibility Criteria

Criteria

Ages Eligible for Study:

16 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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:

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;
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.