Early oral switch therapy in low-risk Staphylococcus aureus bloodstream infection (SABATO): study protocol for a randomized controlled trial

Achim J Kaasch, Gerd Fätkenheuer, Reinhild Prinz-Langenohl, Ursula Paulus, Martin Hellmich, Verena Weiß, Norma Jung, Siegbert Rieg, Winfried V Kern, Harald Seifert, SABATO trial group (with linked authorship to the individuals in the Acknowledgements section), Gerd Fätkenheuer, Norma Jung, Achim J Kaasch, Harald Seifert, Martin Hellmich, Verena Weiß, Karl Lewalter, Sebastian Lemmen, Cornelis Stijnis, Jan van der Meer, Alex Soriano, Laura Morata Ruiz, Keikawus Arastéh, Hartmut Stocker, Jan Kluytmans, Jacobien Veenemans, Hans-Reinhard Brodt, Christoph Stephan, Timo Wolf, Johanna Kessel, Winfried V Kern, Siegbert Rieg, Insa Joost, Bhanu Sinha, Sander van Assen, Kasper Wilting, Tobias Welte, Christiane Mölgen, Julia Freise Frank Brunkhorst, Mathias Pletz, Stefan Hagel, Christian Becker, Thomas Frieling, Katrin Kösters, Stefan Reuter, Mikai Hsiao, Jan Rupp, Klaus Dalhoff, David Turner, Susan Snape, Shanika Crusz, Pradhib Venkatesan, Bernd Salzberger, Frank Hanses, Jesùs Rodriguez-Baño, Adoración Valiente Méndez, Luis Eduardo López Cortés, José Miguel Cisneros, Maria Dolores Navarro-Amuedo, Marc Bonten, Jan Jelrik Oosterheert, Miquel Ekkelenkamp, Achim J Kaasch, Gerd Fätkenheuer, Reinhild Prinz-Langenohl, Ursula Paulus, Martin Hellmich, Verena Weiß, Norma Jung, Siegbert Rieg, Winfried V Kern, Harald Seifert, SABATO trial group (with linked authorship to the individuals in the Acknowledgements section), Gerd Fätkenheuer, Norma Jung, Achim J Kaasch, Harald Seifert, Martin Hellmich, Verena Weiß, Karl Lewalter, Sebastian Lemmen, Cornelis Stijnis, Jan van der Meer, Alex Soriano, Laura Morata Ruiz, Keikawus Arastéh, Hartmut Stocker, Jan Kluytmans, Jacobien Veenemans, Hans-Reinhard Brodt, Christoph Stephan, Timo Wolf, Johanna Kessel, Winfried V Kern, Siegbert Rieg, Insa Joost, Bhanu Sinha, Sander van Assen, Kasper Wilting, Tobias Welte, Christiane Mölgen, Julia Freise Frank Brunkhorst, Mathias Pletz, Stefan Hagel, Christian Becker, Thomas Frieling, Katrin Kösters, Stefan Reuter, Mikai Hsiao, Jan Rupp, Klaus Dalhoff, David Turner, Susan Snape, Shanika Crusz, Pradhib Venkatesan, Bernd Salzberger, Frank Hanses, Jesùs Rodriguez-Baño, Adoración Valiente Méndez, Luis Eduardo López Cortés, José Miguel Cisneros, Maria Dolores Navarro-Amuedo, Marc Bonten, Jan Jelrik Oosterheert, Miquel Ekkelenkamp

Abstract

Background: Current guidelines recommend that patients with Staphylococcus aureus bloodstream infection (SAB) are treated with long courses of intravenous antimicrobial therapy. This serves to avoid SAB-related complications such as relapses, local extension and distant metastatic foci. However, in certain clinical scenarios, the incidence of SAB-related complications is low. Patients with a low-risk for complications may thus benefit from an early switch to oral medication through earlier discharge and fewer complications of intravenous therapy. The major objective for the SABATO trial is to demonstrate that in patients with low-risk SAB a switch from intravenous to oral antimicrobial therapy (oral switch therapy, OST) is non-inferior to a conventional course of intravenous therapy (intravenous standard therapy, IST).

Methods/design: The trial is designed as randomized, parallel-group, observer-blinded, clinical non-inferiority trial. The primary endpoint is the occurrence of a SAB-related complication (relapsing SAB, deep-seated infection, and attributable mortality) within 90 days. Secondary endpoints are the length of hospital stay; 14-day, 30-day, and 90-day mortality; and complications of intravenous therapy. Patients with SAB who have received 5 to 7 full days of adequate intravenous antimicrobial therapy are eligible. Main exclusion criteria are polymicrobial bloodstream infection, signs and symptoms of complicated SAB (deep-seated infection, hematogenous dissemination, septic shock, and prolonged bacteremia), the presence of a non-removable foreign body, and severe comorbidity. Patients will receive either OST or IST with a protocol-approved antimicrobial and are followed up for 90 days. Four hundred thirty patients will be randomized 1:1 in two study arms. Efficacy regarding incidence of SAB-related complications is tested sequentially with a non-inferiority margin of 10 and 5 percentage points.

Discussion: The SABATO trial assesses whether early oral switch therapy is safe and effective for patients with low-risk SAB. Regardless of the result, this pragmatic trial will strongly influence the standard of care in SAB.

Trial registration: ClinicalTrials.gov NCT01792804 registered 13 February 2013; German Clinical trials register DRKS00004741 registered 4 October 2013, EudraCT 2013-000577-77 . First patient randomized on 20 December 2013.

Figures

Fig. 1
Fig. 1
Trial flowchart
Fig. 2
Fig. 2
Analysis sets

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Source: PubMed

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