Oral Switch During Treatment of Left-sided Endocarditis Due to Multi-susceptible Staphylococcus (Relais Oral Dans le Traitement Des Endocardites à Staphylocoques Multi-sensibles)
Overview
- Phase
- Phase 3
- Intervention
- Levofloxacin
- Conditions
- Infective Endocarditis
- Sponsor
- University Hospital, Tours
- Enrollment
- 162
- Locations
- 45
- Primary Endpoint
- Treatment failure
- Status
- Completed
- Last Updated
- 2 months ago
Overview
Brief Summary
Infective endocarditis (IE) is a serious infection with a significant burden for patients and hospitals (in France, median length of hospital stay = 43 days), partly due to the long duration of intravenous (IV) antibacterial treatment recommended by international guidelines, between 4 and 6 weeks in most situations.
A recent survey of practices regarding the management of IE in France showed that a switch from IV to oral antibiotics is feasible, when patients with left-sided Staphylococcus IE are stable after an initial course of IV antibiotic treatment, with or without valvular surgery.
These practices have not been associated with unfavourable outcome, while significantly reducing the duration and cost of hospitalization, the risk of nosocomial infection, and patients' discomfort.
There has been no randomized controlled trial (RCT) in the field of IE over the last 20 years; current guidelines are mostly based on expert advice, in vitro studies, animal experiments, or clinical studies performed before the 90's.
The RODEO 1 project is an unprecedented opportunity to bring back evidence-based medicine in the field of IE.
Most experts acknowledge that the pharmacological PK/PD characteristics of antibiotics such as fluoroquinolones and rifampicin allow a high level of efficacy in the treatment of IE when orally administrated after an IV period of induction.
It's needed to conduct RCTs that clearly demonstrate the clinical non-inferiority of this strategy for multisusceptible staphylococci with a benefit regarding costs.
The RODEO 1 project corresponds to one pragmatic trial assessing the impact of a switch strategy, making it a comparative effectiveness trial that should be able to feed the next revision of IE international guidelines and to change practices in IE management.
Detailed Description
The RODEO 1 study is designed to determine the safety and efficacy of partial oral treatment of IE compared with traditional full-length parenteral treatment. Our primary objective is to demonstrate that in patients with left-sided multi-susceptible Staphylococcus who have received at least 10 days of IV antibiotic treatment with or without valvular surgery, a switch to an oral combination of rifampicin and fluoroquinolones between Day 10 and Day 28 after initiation of the IV antibiotic treatment, is not inferior to the continuation of the conventional IV antibiotic treatment regarding to treatment failure within 3 months after the end of antibiotic treatment. Nationwide, noninferiority, multicenter, randomized, controlled, open-label trials. Randomisation will only be offered to patients who have received at least 10 days of IV conventional antibiotic treatment of IE, and fulfil the inclusion criteria. Randomisation will take place between Day 10 and Day 28 after initiation of parenteral antibiotic therapy or valvular surgery, thus ensuring to have at least 14 days of oral therapy in the experimental group. Patients will be eligible whether they have undergone valvular surgery or not. This will imply that surgery procedure prior to randomisation will be heterogeneous, but randomisation will be stratified on the requirement of valvular surgery as part of the treatment of the current episode of IE or not.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Left-sided IE (Defined according to Duke criteria) on native or prosthetic valve
- •due to one isolate of Staphylococcus sp. (S. aureus or coagulase negative staphylococci, CNS) susceptible to levofloxacin and rifampicin
- •in an adult ≥18 year old
- •appropriate parenteral antibiotics treatment received for at least 10 days
- •in case of valvular surgery, appropriate parenteral antibiotics treatment received for at least 10 days after valvular surgery
- •planned duration of antibiotics will extend for at least 14 days at the time of randomisation i.e. a potential switch to oral treatment between Day 10 and Day 28 thus ensuring to have at least 14 days of oral therapy remaining in the experimental group
- •apyrexia (temperature \< 38°C) at each time point during the last 48 hours (at least two measures/day) at the time of randomisation
- •blood cultures have been sterile for at least 5 days at the time of randomisation
- •informed, written consent obtained from patient
- •subject covered by or having the rights to French social security
Exclusion Criteria
- •body mass index \<15 kg/m² or \> 40 kg/m²
- •glomerular filtration rate \< 50 ml/min/1,73m²
- •patient unable or unwilling to take oral treatment (digestive intolerance, significant malabsorption) at the time of randomisation
- •expected difficulties regarding compliance with oral antibiotic treatment or follow-up (e.g. severe cognitive impairment, severe psychiatric disease...)
- •patient without entourage to support and watch him at discharge
- •valvular surgery planned within the next 6 months
- •patients with cardiac devices (pace-maker, implantable cardiac defibrillator) and suspected device-related IE (vegetation on the leads) if removal of the device was not performed
- •breast feeding or pregnant women, or women on childbearing age without effective contraception
- •expected duration of follow-up \< 7 months at the time of randomisation (e.g. expected life expectancy \< 7 months, patient living abroad...)
- •past medical history of IE in the last 3 months
Arms & Interventions
Oral switch treatment
Oral switch to the combination of levofloxacin and rifampicin
Intervention: Levofloxacin
Oral switch treatment
Oral switch to the combination of levofloxacin and rifampicin
Intervention: Rifampicin
Conventional IV treatment according to european guidelines
Conventional IV treatment of staphylococci IE (European guidelines 2015)
Intervention: Conventional IV treatment of staphylococci IE following European guidelines 2015 including cloxacilline, oxacilline,gentamicine,vancomycine,rifampicine
Outcomes
Primary Outcomes
Treatment failure
Time Frame: up to 3 months after the end of antibiotic treatment
Failure is a composite outcome defined by death from all causes and/or symptomatic embolic events and/or unplanned valvular surgery and/or a microbiological relapse (with the primary pathogen).
Secondary Outcomes
- microbiological relapse with a different pathogen from the primary pathogen(up to 6 months after the end of antibiotic treatment)
- Echocardiography(up to 6 months after the end of antibiotic treatment)
- Catheter related adverse events(up to 6 months after the end of antibiotic treatment)
- number of symptomatic embolic events(up to 6 months after the end of antibiotic treatment)
- Number of participants with an antibiotic modification(up to the end of antibiotic treatment)
- death from all-cause(up to 6 months after the end of antibiotic treatment)
- unplanned valvular surgery(up to 6 months after the end of antibiotic treatment)
- other healthcare-acquired infections(up to 6 months after the end of antibiotic treatment)
- number of participants with a switch back from oral to IV antibiotic treatment(up to the end of antibiotic treatment)
- relapse of positive blood cultures(up to 6 months after the end of antibiotic treatment)
- Quality of life(up to 6 months after the end of antibiotic treatment)
- Compliance with oral antibiotic treatment(up to 4 weeks after randomisation)
- Cost per patient(up to 6 months after the end of antibiotic treatment)
- Budget impact analysis (BIA)(up to 6 months after the end of antibiotic treatment)
- Length of hospital stay(up to 6 months after the end of antibiotic treatment)
- Utility score and incremental cost-utility ratio (ICUR)(up to 6 months after the end of antibiotic treatment)
- Residual concentration of antibiotics(7 days)
- Biological collection for further analysis on endocarditis(up to 6 months after the end of antibiotic treatment)