search
Back to results

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

Primary Purpose

Neutropenia, Febrile

Status
Not yet recruiting
Phase
Phase 4
Locations
Study Type
Interventional
Intervention
Comparison short vs extended EBAT treatment group
Sponsored by
Universitaire Ziekenhuizen KU Leuven
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional supportive care trial for Neutropenia, Febrile focused on measuring Neutropenia, Leukemia, Stem Cell Transplant Complications, Infections

Eligibility Criteria

16 Years - undefined (Child, Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Experimental

    Active Comparator

    Arm Label

    Short treatment group

    Extended treatment group

    Arm 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.

    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.

    Outcomes

    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.

    Secondary Outcome Measures

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

    Full Information

    First Posted
    June 21, 2023
    Last Updated
    June 21, 2023
    Sponsor
    Universitaire Ziekenhuizen KU Leuven
    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
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT05926063
    Brief Title
    Stopping Antibiotics After 3 Days for the Treatment of High-risk FEbrile Neutropenia
    Acronym
    SAFE
    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

    2. Study Status

    Record Verification Date
    June 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    July 2023 (Anticipated)
    Primary Completion Date
    July 2026 (Anticipated)
    Study Completion Date
    July 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Sponsor
    Name of the Sponsor
    Universitaire Ziekenhuizen KU Leuven
    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

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Product Manufactured in and Exported from the U.S.
    No

    5. 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.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Neutropenia, Febrile
    Keywords
    Neutropenia, Leukemia, Stem Cell Transplant Complications, Infections

    7. Study Design

    Primary Purpose
    Supportive Care
    Study Phase
    Phase 4
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    410 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Short treatment group
    Arm Type
    Experimental
    Arm 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.
    Arm Title
    Extended treatment group
    Arm Type
    Active Comparator
    Arm 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.
    Intervention Type
    Other
    Intervention Name(s)
    Comparison short vs extended EBAT treatment group
    Intervention Description
    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).
    Primary Outcome Measure Information:
    Title
    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.
    Time Frame
    42 days
    Secondary Outcome Measure Information:
    Title
    Incidence of bacteraemia within 42 days after randomisation
    Time Frame
    42 days
    Title
    Clinically documented infections
    Time Frame
    42 days
    Title
    Number of documented bacterial infections
    Time Frame
    42 days
    Title
    Total days of non-prophylactic antibiotics given to the patient at engraftment
    Time Frame
    42 days
    Title
    Total numbers of antibiotic switches before neutrophil recovery
    Time Frame
    42 days
    Title
    Incidence of Clostridium difficile infection
    Time Frame
    42 days
    Title
    Incidence, severity and duration of diarrhea
    Time Frame
    42 days
    Title
    Incidence of candidemia
    Time Frame
    42 days
    Title
    Length of hospital stay in the first 42 days after randomization
    Time Frame
    42 days
    Title
    Number of patients admitted to the ICU within 42 days after randomisation
    Time Frame
    42 days
    Title
    Number of readmissions within 42 days
    Time Frame
    42 days
    Title
    Number of patients with a culture (surveillance or diagnostic culture) positive for resistant bacteria: VRE; ESBL; MRSA; and/or CPE
    Time Frame
    42 days
    Title
    Duration of hospitalization
    Time Frame
    42 days
    Title
    Number of patients in the short treatment arm with ongoing fever at time of EBAT stop
    Time Frame
    42 days
    Title
    Incidence of acute GVHD (grade II or higher) in the transplanted study population
    Time Frame
    42 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    16 Years
    Accepts Healthy Volunteers
    No
    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: 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.
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Robina Aerts, MD
    Phone
    +32 16 34 48 77
    Email
    robina.aerts@kuleuven.be
    First Name & Middle Initial & Last Name or Official Title & Degree
    Johan Maertens, MD, PhD
    Phone
    +32 16 34 66 70
    Email
    johan.maertens@uzleuven.be
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Johan Maertens, MD, PhD
    Organizational Affiliation
    Universitaire Ziekenhuizen KU Leuven
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Learn more about this trial

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

    We'll reach out to this number within 24 hrs