Safe shortening of antibiotic treatment duration for complicated Staphylococcus aureus bacteraemia (SAFE trial): protocol for a randomised, controlled, open-label, non-inferiority trial comparing 4 and 6 weeks of antibiotic treatment

Safe shortening of antibiotic treatment duration for complicated Staphylococcus aureus bacteraemia (SAFE trial): protocol for a randomised, controlled, open-label, non-inferiority trial comparing 4 and 6 weeks of antibiotic treatment

IntroductionA major knowledge gap in the treatment of complicated Staphylococcus aureus bacteraemia (SAB) is the optimal duration of antibiotic therapy. Safe shortening of antibiotic therapy has the potential to reduce adverse drug events, length of hospital stay and costs. The objective of the SAFE...

Full description

Saved in:
Bibliographic Details
Published in:BMJ open Vol. 13; no. 4; p. e068295
Main Authors: Buis, DTP, van Werkhoven, CH, van Agtmael, MA, Bax, HI, Berrevoets, M, de Boer, MGJ, Bonten, MJM, Bosmans, JE, Branger, J, Douiyeb, S, Gelinck, LBS, Jong, E, Lammers, AJJ, Van der Meer, JTM, Oosterheert, JJ, Sieswerda, E, Soetekouw, R, Stalenhoef, JE, Van der Vaart, TW, Bij de Vaate, EA, Verkaik, NJ, Van Vonderen, MGA, De Vries, PJ, Prins, JM, Sigaloff, KCE, Botman, E, Van den Broek, A, Buitenhuis, L, Buitenwerf, E, Cents, A S, Engels, N, Hanssen, J L J, Meinders, A J, Mollema, F P N, Nagelmaker, L, van Doorn-Schepens, M L M, Roescher, N, Thomopoulos, P, Timmer, M, van der Wiel, B
Format: Journal Article
Language:English
Published: England British Medical Journal Publishing Group 21-04-2023
BMJ Publishing Group LTD
BMJ Publishing Group
Series:Protocol
Subjects:
Abscesses
Adult
Anti-Bacterial Agents
Antibiotics
Bacteremia - microbiology
Bacterial infections
bacteriology
Clinical medicine
Duration of Therapy
Endocarditis
Fever
Humans
Infectious Diseases
internal medicine
Intravenous therapy
Metastasis
Multicenter Studies as Topic
Prostheses
Randomized Controlled Trials as Topic
Staphylococcal Infections - drug therapy
Staphylococcal Infections - microbiology
Staphylococcus aureus
Staphylococcus infections
Tomography
Ultrasonic imaging
Netherlands
internal medicine
bacteriology
infectious diseases
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:IntroductionA major knowledge gap in the treatment of complicated Staphylococcus aureus bacteraemia (SAB) is the optimal duration of antibiotic therapy. Safe shortening of antibiotic therapy has the potential to reduce adverse drug events, length of hospital stay and costs. The objective of the SAFE trial is to evaluate whether 4 weeks of antibiotic therapy is non-inferior to 6 weeks in patients with complicated SAB.Methods and analysisThe SAFE-trial is a multicentre, non-inferiority, open-label, parallel group, randomised controlled trial evaluating 4 versus 6 weeks of antibiotic therapy for complicated SAB. The study is performed in 15 university hospitals and general hospitals in the Netherlands. Eligible patients are adults with methicillin-susceptible SAB with evidence of deep-seated or metastatic infection and/or predictors of complicated SAB. Only patients with a satisfactory clinical response to initial antibiotic treatment are included. Patients with infected prosthetic material or an undrained abscess of 5 cm or more at day 14 of adequate antibiotic treatment are excluded. Primary outcome is success of therapy after 180 days, a combined endpoint of survival without evidence of microbiologically confirmed disease relapse. Assuming a primary endpoint occurrence of 90% in the 6 weeks group, a non-inferiority margin of 7.5% is used. Enrolment of 396 patients in total is required to demonstrate non-inferiority of shorter antibiotic therapy with a power of 80%. Currently, 152 patients are enrolled in the study.Ethics and disseminationThis is the first randomised controlled trial evaluating duration of antibiotic therapy for complicated SAB. Non-inferiority of 4 weeks of treatment would allow shortening of treatment duration in selected patients with complicated SAB. This study is approved by the Medical Ethics Committee VUmc (Amsterdam, the Netherlands) and registered under NL8347 (the Netherlands Trial Register). Results of the study will be published in a peer-reviewed journal.Trial registration numberNL8347 (the Netherlands Trial Register).
Bibliography:Protocol
ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
ObjectType-Undefined-3
ISSN:2044-6055
2044-6055
DOI:10.1136/bmjopen-2022-068295