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

  • STATUS
    Recruiting
  • End date
    Sep 27, 2024
  • participants needed
    324
  • sponsor
    University Hospital, Tours
Updated on 27 May 2021
Investigator
Jean-Pierre BRU, Dr
Primary Contact
Infectiologie, m decine interne et m decine des voyages, CH d'Annecy (1.6 mi away) Contact
+71 other location
antibiotic therapy
antibiotics
rifampicin
discomfort
vancomycin
antibacterial
blood culture

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.

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.

Details
Condition Endocarditis, Bacterial Endocarditis, Heart disease, Cardiac Disease
Treatment rifampicin, levofloxacin, Conventional IV treatment of staphylococci IE following European guidelines 2015 including cloxacilline, oxacilline,gentamicine,vancomycine,rifampicine
Clinical Study IdentifierNCT02701608
SponsorUniversity Hospital, Tours
Last Modified on27 May 2021

Eligibility

Yes No Not Sure

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 < 38C) 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/m or > 40 kg/m
glomerular filtration rate < 50 ml/min/1,73m
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
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. fluoroquinolones or rifampicin ) - including anticipated non-manageable drug interactions with rifampicin, and allergy
Clear my responses

How to participate?

Step 1 Connect with a site
What happens next?
  • You can expect the study team to contact you via email or phone in the next few days.
  • Sign up as volunteer to help accelerate the development of new treatments and to get notified about similar trials.

You are contacting

Investigator Avatar
Name

Primary Contact

site
Name

0/250
Preferred Language
Other Language
Please verify that you are not a bot.

Additional screening procedures may be conducted by the study team before you can be confirmed eligible to participate.

Learn more

If you are confirmed eligible after full screening, you will be required to understand and sign the informed consent if you decide to enroll in the study. Once enrolled you may be asked to make scheduled visits over a period of time.

Learn more

Complete your scheduled study participation activities and then you are done. You may receive summary of study results if provided by the sponsor.

Learn more

Similar trials to consider

Loading...

Browse trials for

Not finding what you're looking for?

Every year hundreds of thousands of volunteers step forward to participate in research. Sign up as a volunteer and receive email notifications when clinical trials are posted in the medical category of interest to you.

Sign up as volunteer

user name

Added by • 

 • 

Private

Reply by • Private
Loading...

Lorem ipsum dolor sit amet consectetur, adipisicing elit. Ipsa vel nobis alias. Quae eveniet velit voluptate quo doloribus maxime et dicta in sequi, corporis quod. Ea, dolor eius? Dolore, vel!

  The passcode will expire in None.
Loading...

No annotations made yet

Add a private note
  • abc Select a piece of text from the left.
  • Add notes visible only to you.
  • Send it to people through a passcode protected link.
Add a private note