Safe shortening of antibiotic treatment duration for complicated Staphylococcus aureus bacteremia (SAFE-trial)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Stichting Amsterdam UMC

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

17 Aug 2020 → ongoing

Decision date (initial)

2024-08-14

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515398-90-01

EudraCT number

2019-004921-25

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To determine whether 4 weeks of total antibiotic treatment duration is non-inferior to 6 weeks in patients with complicated SAB who have responded well to the initial treatment.

Conditions and MedDRA coding

Staphylococcus aureus bacteremia

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 4

1. Adults with methicillin-sensitive complicated SAB, defined as having at least one blood culture positive for S. aureus and one of the following conditions:
2. Evidence of organ involvement and/or deep-seated infection. Examples of clinical diagnoses are: endocarditis, spondylodiscitis, arthritis, intravascular infection, abscess, and/or metastatic complications.
3. Predictors of complicated SAB, defined as presence of at least one of the following risk factors for complicated SAB: a. community acquisition; b. delay > 48 hours of adequate treatment after the initial positive blood culture; c. positive follow-up blood culture > 48 hours after initiation of adequate treatment; d. persistence of fever at 72 hours after the initial positive blood culture (temperature > 38 degrees for two consecutive calendar days, measured at two time points with at least 24 hours interval, between 2 days and 7 days after the initial positive blood culture) e.unknown primary source of infection (porte d’entrée).
4. 1) Satisfactory clinical response to initial treatment, defined as meeting all of the following: a) Negative blood culture for S. aureus on day 8 of adequate antibiotic treatment, defined as intravenous administration of an antibiotic agent with in-vitro activity against the cultured S. aureus. In absence of blood culture sampling on day 8, the date of first negative blood culture is the midpoint between the last positive blood culture for S. aureus and the first negative blood culture for S. aureus. b) Negative intra-operative cultures in patients with S. aureus native valve endocarditis who underwent cardiac surgery. c) C-reactive protein (CRP) decline to at least 50% below peak level or to <30 mg/L within 14 days of adequate antibiotic treatment. A high CRP due to an evident other cause, for example, an unrelated infection, is disregarded in this definition. d) Absence of fever (temperature < 38 degrees for two consecutive calendar days, measured at two time points with at least 24 hours interval) between 7 and 14 days of adequate antibiotic treatment. Fever due to unrelated, intercurrent infection (e.g. respiratory tract infection) is disregarded in this definition.

Exclusion criteria 3

1. Infected prosthetic heart valve or other infected prosthetic material which is not removed within 14 days of antibiotic therapy, as manifested by either one of the following: a) Clinical suspicion of infected prosthetic material; b) Transthoracic echocardiogram (TTE) or transesophageal echocardiogram (TEE) positive for prosthetic valve or device endocarditis; c) Positron emission tomography/computed tomography (PET/CT) scan positive for infection of prosthetic material (including prosthetic heart valve, cardiac device, vascular prosthesis or joint prosthesis).
2. Presence of undrained abscess of 5 cm or more in one direction on radiological imaging at day 14 of antibiotic treatment .
3. Pregnancy or lactation.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary outcome is success of therapy, defined at 180 days after randomization by presence of the following: 1. Patient alive. 2. No evidence of microbiologically confirmed disease relapse, defined as symptoms and/or signs of infection, after initial clinical improvement, with S. aureus isolated from blood or another normally sterile site (e.g. joint fluid, tissue) by conventional culture.

Investigational products

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

Test 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Stichting Amsterdam UMC

Sponsor organisation

Stichting Amsterdam UMC

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Stichting Amsterdam UMC

Contact name

Jan Prins

Public contact point

Organisation

Stichting Amsterdam UMC

Contact name

Jan Prins

Locations

1 EU/EEA country · 15 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 9 files

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

Application history

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