Oral Switch During Treatment of Left-sided Endocarditis Due to Multi-susceptible Streptococcus

The RODEO 2 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 Streptococcus-Enterococcus IE who have received at least 10 days of IV antibiotic treatment with or without valvular surgery, a switch to an oral combination of amoxicillin 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.

Inclusion criteria

• Left-sided IE (Defined according to Duke criteria) on native or prosthetic valve
• due to one isolate of Streptococcus/Enterococcus sp. susceptible to amoxicillin (MCI ≤ 0.5 mg/l)
• 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 < 30 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
• for 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
• other infection requiring parenteral antibiotic therapy
• taking of an estrogen-progesterone treatment interacting with rifampicin
• patient with contra-indication to oral antibiotics administered in the experimental arm (i.e. amoxicillin) - including anticipated non-manageable drug interactions, and allergy.