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
Introduction A 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 SAF...
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2023-04-01
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| author | N Roescher JM Prins JTM van der Meer HI Bax R Soetekouw MGJ de Boer LBS Gelinck JJ Oosterheert MA van Agtmael M Berrevoets DTP Buis CH van Werkhoven MJM Bonten JE Bosmans J Branger S Douiyeb E Jong AJJ Lammers E Sieswerda JE Stalenhoef TW Van der Vaart EA Bij de Vaate NJ Verkaik MGA Van Vonderen PJ De Vries KCE Sigaloff E Botman A Van den Broek L Buitenhuis E Buitenwerf A S Cents N Engels J L J Hanssen A J Meinders F P N Mollema L Nagelmaker M L M van Doorn-Schepens P Thomopoulos M Timmer B van der Wiel |
| author_facet | N Roescher JM Prins JTM van der Meer HI Bax R Soetekouw MGJ de Boer LBS Gelinck JJ Oosterheert MA van Agtmael M Berrevoets DTP Buis CH van Werkhoven MJM Bonten JE Bosmans J Branger S Douiyeb E Jong AJJ Lammers E Sieswerda JE Stalenhoef TW Van der Vaart EA Bij de Vaate NJ Verkaik MGA Van Vonderen PJ De Vries KCE Sigaloff E Botman A Van den Broek L Buitenhuis E Buitenwerf A S Cents N Engels J L J Hanssen A J Meinders F P N Mollema L Nagelmaker M L M van Doorn-Schepens P Thomopoulos M Timmer B van der Wiel |
| author_sort | N Roescher |
| collection | DOAJ |
| description | Introduction A 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 analysis The 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 dissemination This 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 number NL8347 (the Netherlands Trial Register). |
| format | Article |
| id | doaj-art-cf2fa20a75a4412a9dbd8b21a6ce2c68 |
| institution | OA Journals |
| issn | 2044-6055 |
| language | English |
| publishDate | 2023-04-01 |
| publisher | BMJ Publishing Group |
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| series | BMJ Open |
| spelling | doaj-art-cf2fa20a75a4412a9dbd8b21a6ce2c682025-08-20T02:12:34ZengBMJ Publishing GroupBMJ Open2044-60552023-04-0113410.1136/bmjopen-2022-068295Safe 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 treatmentN RoescherJM Prins0JTM van der Meer1HI Bax2R Soetekouw3MGJ de Boer4LBS Gelinck5JJ Oosterheert6MA van Agtmael7M Berrevoets8DTP Buis9CH van Werkhoven10MJM Bonten11JE Bosmans12J Branger13S Douiyeb14E Jong15AJJ Lammers16E Sieswerda17JE Stalenhoef18TW Van der Vaart19EA Bij de Vaate20NJ Verkaik21MGA Van Vonderen22PJ De Vries23KCE Sigaloff24E BotmanA Van den BroekL BuitenhuisE BuitenwerfA S CentsN EngelsJ L J HanssenA J MeindersF P N MollemaL NagelmakerM L M van Doorn-SchepensP ThomopoulosM TimmerB van der WielDepartment of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity, Amsterdam UMC Locatie VUmc, Amsterdam, The NetherlandsDepartment of Internal Medicine, Division of Infectious Diseases, Amsterdam UMC Locatie AMC, Amsterdam, The NetherlandsDepartment of Internal Medicine, Section of Infectious Diseases, Erasmus Medical Center, Rotterdam, The NetherlandsDepartment of Internal Medicine, Spaarne Gasthuis, Haarlem/Hoofddorp, The NetherlandsDepartment of Infectious Diseases, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Internal Medicine, Haaglanden Medisch Centrum, Den Haag, The NetherlandsDepartment of Internal Medicine, Infectious Diseases, UMC Utrecht, Utrecht, The NetherlandsDepartment of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity, Amsterdam UMC Locatie VUmc, Amsterdam, The NetherlandsDepartment of Internal Medicine, Elisabeth twee-steden Hospital, Tilburg, The NetherlandsDepartment of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity, Amsterdam UMC Locatie VUmc, Amsterdam, The NetherlandsJulius Center for Health Sciences and Primary Care, UMC Utrecht, Utrecht, The NetherlandsJulius Center for Health Sciences and Primary Care, UMC Utrecht, Utrecht, The NetherlandsDepartment of Health Sciences, Faculty of Science, Amsterdam Public Health research institute, VU University Amsterdam, Amsterdam, The NetherlandsDepartment of Internal Medicine, Flevohospital, Almere, The NetherlandsDepartment of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity, Amsterdam UMC Locatie VUmc, Amsterdam, The NetherlandsDepartment of Internal Medicine, Meander Medisch Centrum, Amersfoort, The NetherlandsDepartment of Internal medicine & Infectious Diseases, Isala Zwolle, Zwolle, The NetherlandsJulius Center for Health Sciences and Primary Care, UMC Utrecht, Utrecht, The NetherlandsDepartment of Internal Medicine, OLVG, Amsterdam, The NetherlandsDepartment of Internal Medicine, Division of Infectious Diseases, Amsterdam UMC Locatie AMC, Amsterdam, The NetherlandsDepartment of Internal Medicine, St. Antonius Hospital, Nieuwegein, The NetherlandsDepartment of Medical Microbiology and Infectious Diseases, Erasmus MC, Rotterdam, The NetherlandsMedisch Centrum Leeuwarden, Leeuwarden, The NetherlandsDepartment of Internal Medicine, Tergooi Hospital, Hilversum, The NetherlandsDepartment of Internal Medicine, Division of Infectious Diseases, Amsterdam Institute for Infection and Immunity, Amsterdam UMC Locatie VUmc, Amsterdam, The NetherlandsIntroduction A 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 analysis The 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 dissemination This 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 number NL8347 (the Netherlands Trial Register).https://bmjopen.bmj.com/content/13/4/e068295.full |
| spellingShingle | N Roescher JM Prins JTM van der Meer HI Bax R Soetekouw MGJ de Boer LBS Gelinck JJ Oosterheert MA van Agtmael M Berrevoets DTP Buis CH van Werkhoven MJM Bonten JE Bosmans J Branger S Douiyeb E Jong AJJ Lammers E Sieswerda JE Stalenhoef TW Van der Vaart EA Bij de Vaate NJ Verkaik MGA Van Vonderen PJ De Vries KCE Sigaloff E Botman A Van den Broek L Buitenhuis E Buitenwerf A S Cents N Engels J L J Hanssen A J Meinders F P N Mollema L Nagelmaker M L M van Doorn-Schepens P Thomopoulos M Timmer B van der Wiel 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 BMJ Open |
| title | 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 |
| title_full | 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 |
| title_fullStr | 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 |
| title_full_unstemmed | 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 |
| title_short | 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 |
| title_sort | 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 |
| url | https://bmjopen.bmj.com/content/13/4/e068295.full |
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