SAFE study: Stopping Antibiotics after 3 days for the treatment of FEbrile Neutropenia in Haematology patients, a randomized open-label non-inferiority trial

Overview

Sponsor-declared trial summary

Key facts

Sponsor

UZ Leuven

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Bacterial Infections and Mycoses [C01]

Trial duration

16 Feb 2024 → 14 May 2026

Decision date (initial)

2023-08-23

Transition trial

No

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

Funding sources

Kom op tegen Kanker

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Others

To assess if a strategy of short antibiotic treatment (72h) with a broad-spectrum antibiotic is as safe as extended treatment of high-risk febrile neutropenia in hematology patients.

Conditions and MedDRA coding

Febrile neutropenia

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 5

1. Voluntary written informed consent of the participant or their legally authorized representative has been obtained prior to any screening procedures
2. Age older than 16 years
3. 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.
4. Expected longstanding (≥ 7 days) neutropenia (absolute neutrophil count < 0.5x10^9/L)
5. Expected length of hospital stay of at least 10 days

Exclusion criteria 9

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

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 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 endpoints 15

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

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UZ Leuven

Sponsor organisation

UZ Leuven

Address

Herestraat 49

City

Leuven

Postcode

3000

Country

Belgium

Scientific contact point

Organisation

UZ Leuven

Contact name

Robina Aerts

Public contact point

Organisation

UZ Leuven

Contact name

SAFE Study Team

Locations

1 EU/EEA country · 9 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 31 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

6 submissions — initial application plus substantial / non-substantial modifications