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

NCT ID: NCT05926063

Last Updated: 2024-03-08

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE4
• Total Enrollment: 410 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2024-02-26
• Study Completion Date: 2026-07-31

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.

Conditions

Neutropenia, Febrile

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Comparison short vs extended EBAT treatment group

Intervention Type: OTHER

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).

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.

Group Type: ACTIVE_COMPARATOR

Comparison short vs extended EBAT treatment group

Intervention Type: OTHER

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).

Interventions

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).

Intervention Type: OTHER

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.

• Minimum Eligible Age: 16 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital, Ghent

OTHER

Sponsor Role: collaborator

Universitair Ziekenhuis Brussel

OTHER

Sponsor Role: collaborator

University Hospital, Antwerp

OTHER

Sponsor Role: collaborator

AZ Sint-Jan AV

OTHER

Sponsor Role: collaborator

Centre Hospitalier Universitaire de Liege

OTHER

Sponsor Role: collaborator

Cliniques universitaires Saint-Luc- Université Catholique de Louvain

OTHER

Sponsor Role: collaborator

Universitaire Ziekenhuizen KU Leuven

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Johan Maertens, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Universitaire Ziekenhuizen KU Leuven

Locations

University Hospitals Leuven

Leuven, Vlaams-Brabant, Belgium

Site Status: RECRUITING

Countries

Belgium

Central Contacts

Robina Aerts, MD

Role: CONTACT

robina.aerts@kuleuven.be

+32 16 34 48 77

Johan Maertens, MD, PhD

Role: CONTACT

johan.maertens@uzleuven.be

+32 16 34 66 70

Facility Contacts

Robina Aerts, MD

Role: primary

robina.aerts@kuleuven.be

Yuri Vanbiervliet, MD

Role: backup

yuri.vanbiervliet@uzleuven.be

Other Identifiers

2022-500389-84

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

S66527

Identifier Type: -

Identifier Source: org_study_id