Oral switch versus standard intravenous antibiotic therapy in left-sided endocarditis due to susceptible staphylococci, streptococci or enterococci (RODEO): a protocol for two open-label randomised controlled trials

Adrien Lemaignen, Louis Bernard, Pierre Tattevin, Jean-Pierre Bru, Xavier Duval, Bruno Hoen, Solène Brunet-Houdard, Jean-Luc Mainardi, Agnes Caille, RODEO (Relais Oral Dans le traitement des Endocardites à staphylocoques ou streptOcoques) and AEPEI (Association pour l’Etude et la Prévention de l’Endocardite Infectieuse) study groups, Adrien Lemaignen, Louis Bernard, Pierre Tattevin, Jean-Pierre Bru, Xavier Duval, Bruno Hoen, Solène Brunet-Houdard, Jean-Luc Mainardi, Agnes Caille, RODEO (Relais Oral Dans le traitement des Endocardites à staphylocoques ou streptOcoques) and AEPEI (Association pour l’Etude et la Prévention de l’Endocardite Infectieuse) study groups

Abstract

Introduction: Left-sided infective endocarditis (IE) is a serious infection with a heavy burden for patients and healthcare system. Oral switch after initial intravenous antibiotic therapy may reduce costs and improve patients' discomfort without increasing unfavourable outcomes. We describe the methodology of two simultaneously conducted open-label randomised trials aiming to assess non-inferiority of oral switch as compared with entirely intravenous antibiotic therapy for the treatment of left-sided IE.

Methods and analysis: Two simultaneous multicentre open-label prospective randomised trials assessing non-inferiority of oral switch during antibiotic treatment as compared with entirely intravenous therapy in patients with left-sided IE are ongoing. One trial is dedicated to left-sided IE caused by multisusceptible staphylococci (Relais Oral Dans le traitement des Endocardites à staphylocoques ou streptOcoques (RODEO)-1) and the other is dedicated to left-sided IE caused by susceptible streptococci or enterococci (RODEO-2). It is planned to randomise 324 patients in each trial after an initial course of at least 10 days of intravenous antibiotic therapy either to continue intravenous antibiotic therapy or to switch to oral antibiotic therapy. The primary outcome is treatment failure within 3 months after the end of antibiotic treatment, a composite outcome defined by all-cause death and/or symptomatic embolic events and/or unplanned valvular surgery and/or microbiological relapse (with the primary pathogen). Secondary outcomes include patient quality of life, echocardiographic outcome, costs and efficiency associated with IE care. Statistical analysis will be performed with a non-inferiority margin of 10% and a one-sided 2.5% type I error.

Ethics and dissemination: Written informed consent will be obtained from all participants. This study was approved by Tours Research ethics committee (CPP TOURS-Region Centre-Ouest 1, 2015-R26, 23 February 2016). Study findings will be published in peer-reviewed journals and disseminated through presentation at relevant national and international conferences.

Trial registration number: EudraCT Number: 2015-002371-16 and NCT02701608; NCT02701595.

Keywords: adult; anti-bacterial agents; infective endocarditis; oral administration; randomised controlled trial.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
Study design. IE, infective endocarditis; IV, intravenous.
Figure 2
Figure 2
Study schedule. *Clinical examination will collect the following information: body temperature, blood pressure, heart murmur (new or modified), any infectious site, list and tolerance of any drug, with a special focus on digestive symptoms, rash, neuropsychiatric problems. **Residual concentration of antibiotic treatment is realised only for patients randomised in ‘oral therapy’ group. ATB, antibiotic treatment; EQ5D3L, EuroQol Five Dimensions; IE, infective endocarditis; IV, intravenous.

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