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

Universitaire Ziekenhuizen KU Leuven

Status and phase: Enrolling; Phase 4

Conditions: Neutropenia, Febrile

Treatments: Other: Comparison short vs extended EBAT treatment group

Study type: Interventional

Funder types: Other

Identifiers

NCT05926063

2022-500389-84 (EudraCT Number)

S66527

Details and patient eligibility

About

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.

Enrollment: 410 estimated patients

Sex: All

Ages: 16+ years old

Volunteers: No 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

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.

Trial design

Primary purpose: Supportive Care

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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410 participants in 2 patient groups

Short treatment group

Experimental group

Description:

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.

Treatment:

Other: Comparison short vs extended EBAT treatment group

Extended treatment group

Active Comparator group

Description:

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.

Treatment:

Other: Comparison short vs extended EBAT treatment group