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

NCT ID: NCT02701608

Last Updated: 2021-05-19

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE3

Total Enrollment

324 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-02-29

Study Completion Date

2024-09-30

Brief Summary

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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

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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.

Conditions

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Infective Endocarditis

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Oral switch treatment

Oral switch to the combination of levofloxacin and rifampicin

Group Type EXPERIMENTAL

Levofloxacin

Intervention Type DRUG

levofloxacin 500 mg x1/day (for patients ≤70kg) or levofloxacin 750 mg x1/day (for patients \>70kg)

Rifampicin

Intervention Type DRUG

rifampicin 600mg x1/day (for patients ≤70kg) or rifampicin 900mg x1/day (for patients \>70kg)

Conventional IV treatment according to european guidelines

Conventional IV treatment of staphylococci IE (European guidelines 2015)

Group Type ACTIVE_COMPARATOR

Conventional IV treatment of staphylococci IE following European guidelines 2015 including cloxacilline, oxacilline,gentamicine,vancomycine,rifampicine

Intervention Type PROCEDURE

Conventional IV treatment of staphylococci IE following European guidelines 2015 including cloxacilline, oxacilline,gentamicine,vancomycine,rifampicine

Interventions

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Levofloxacin

levofloxacin 500 mg x1/day (for patients ≤70kg) or levofloxacin 750 mg x1/day (for patients \>70kg)

Intervention Type DRUG

Rifampicin

rifampicin 600mg x1/day (for patients ≤70kg) or rifampicin 900mg x1/day (for patients \>70kg)

Intervention Type DRUG

Conventional IV treatment of staphylococci IE following European guidelines 2015 including cloxacilline, oxacilline,gentamicine,vancomycine,rifampicine

Conventional IV treatment of staphylococci IE following European guidelines 2015 including cloxacilline, oxacilline,gentamicine,vancomycine,rifampicine

Intervention Type PROCEDURE

Other Intervention Names

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Fluoroquinolones

Eligibility Criteria

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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
* 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.
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University Hospital, Tours

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Louis BERNARD, MD,PHD

Role: PRINCIPAL_INVESTIGATOR

CHRU TOURS

Locations

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Service des Maladies infectieuses, Centre Hospitalier du Pays d'Aix

Aix-en-Provence, , France

Site Status WITHDRAWN

Service de court séjour gériatrique - EMG, Centre hospitalier d'Alès

Alès, , France

Site Status WITHDRAWN

Service de Pathologies infectieuses et tropicales, Hôpital Nord, CHU d'Amiens

Amiens, , France

Site Status RECRUITING

CHU ANGERS - Service des maladies infectieuses et tropicales

Angers, , France

Site Status RECRUITING

Service des Maladies infectieuses et Tropicales, Hôpital Jean Minjoz, CHU de Besançon

Besançon, , France

Site Status RECRUITING

Service de Maladies infectieuses et tropicales, Hôpital Avicenne, APHP

Bobigny, , France

Site Status WITHDRAWN

Service de Réanimation médicale, Hôpital St André, CHU de Bordeaux

Bordeaux, , France

Site Status RECRUITING

Service de Médecine interne, Hôpital Ambroise Paré, APHP

Boulogne-Billancourt, , France

Site Status RECRUITING

Service de Maladies infectieuses, Hôpital de la Cavale Blanche

Brest, , France

Site Status WITHDRAWN

Service de Cardiologie, Hôpitall Louis Pradel, Hôpitaux Est, Hospices Civils de Lyon

Bron, , France

Site Status RECRUITING

Service Maladies Infectieuses et tropicales, Hôpital Côte de Nacre, CHU de Caen

Caen, , France

Site Status RECRUITING

Service de Maladies infectieuses et tropicales, médecine interne, CH de Chambéry

Chambéry, , France

Site Status RECRUITING

Service des maladies infectieuses et tropicales, Hôpital G. Montpied, CHU de Clermont-Ferrand

Clermont-Ferrand, , France

Site Status RECRUITING

APHP Henri-Mondor - Service des maladies infectieuses et tropicales

Créteil, , France

Site Status NOT_YET_RECRUITING

Département d'infectiologie, Complexe Bocage, Hôpital d'enfants, CHU de Dijon

Dijon, , France

Site Status RECRUITING

Service de Médecine interne polyvalente et neurologique CH de Douai

Douai, , France

Site Status RECRUITING

Service de Médecine aigue spécifique, Hôpital Raymond Poincaré, APHP

Garches, , France

Site Status RECRUITING

Service de Médecine post-urgence, infectiologie, Site de la Roche sur Yon, CHD Vendée

La Roche-sur-Yon, , France

Site Status RECRUITING

Service de Médecine infectieuse, Hôpital Nord Michallon, CHU de Grenoble

La Tronche, , France

Site Status RECRUITING

Service de Maladies infectieuses et tropicales, et pathologie VIH

Le Chesnay, , France

Site Status WITHDRAWN

APHP BICETRE - Service des maladies infectieuses et tropicales

Le Kremlin-Bicêtre, , France

Site Status ACTIVE_NOT_RECRUITING

Service des Maladies infectieuses et tropicales, CH Le Mans

Le Mans, , France

Site Status RECRUITING

Unité médicale d'infectiologie, Hôpital Huriez, CHU de Lille

Lille, , France

Site Status RECRUITING

Service de Maladies Infectieuses et tropicales, Hôpital Dupuytren, CHU de Limoges

Limoges, , France

Site Status WITHDRAWN

Clinique de la Sauvegarde

Lyon, , France

Site Status RECRUITING

Service de Maladies infectieuses, Hôpital Gui de CHauliac, CHU de Montpellier

Montpellier, , France

Site Status WITHDRAWN

Service de Maladies infectieuses et tropicales, Hôpital Hôtel Dieu, CHU Nantes

Nantes, , France

Site Status RECRUITING

Service d'Infectiologie, Hôpital de l'Archet, CHU de Nice

Nice, , France

Site Status RECRUITING

Service des Maladies infectieuses, CH de Niort

Niort, , France

Site Status RECRUITING

Service des Maladies Infectieuses et Tropicales, Hôpital Carémeau, CHU de Nîmes

Nîmes, , France

Site Status RECRUITING

Service de Maladies infectieuses et tropicales, Hôpital de la Source, CHR Orléans

Orléans, , France

Site Status RECRUITING

APHP St Antoine

Paris, , France

Site Status NOT_YET_RECRUITING

Service de Microbiologie, Hôpital Européen Georges Pompidou, APHP

Paris, , France

Site Status RECRUITING

Service de Maladies infectieuses et tropicales, Hôpital Necker, APHP

Paris, , France

Site Status RECRUITING

Service de Maladies infectieuses, parasitaires et tropicales, Hôpital Bichat, APHP

Paris, , France

Site Status RECRUITING

Institut Mutualiste Montsouris - Service de médecine interne

Paris, , France

Site Status RECRUITING

CH PAU - Service de Médecine interne et Maladies infectieuses

Pau, , France

Site Status ACTIVE_NOT_RECRUITING

Service des Maladies infectieuses et tropicales, CH de Perpignan

Perpignan, , France

Site Status WITHDRAWN

Service de Médecine interne, maladies infectieuses et tropicales, CHU de Poitiers

Poitiers, , France

Site Status RECRUITING

Infectiologie, médecine interne et médecine des voyages, CH d'Annecy

Pringy, , France

Site Status RECRUITING

CH QUIMPER - Service d'infectiologie

Quimper, , France

Site Status RECRUITING

Service de Médecine interne, maladies infectieuses, immunologie clinique, Hôpital R. Debré, CHU de Reims

Reims, , France

Site Status RECRUITING

Service des maladies infectieuses et réanimation médicale, Hôpital Pontchaillou, CHU de Rennes

Rennes, , France

Site Status RECRUITING

Service des Maladies infectieuses et tropicales, Hôpital Charles Nicolle, CHU de Rouen

Rouen, , France

Site Status RECRUITING

Service des Maladie infectieuses et tropicales, Hôpital d'instruction des armées Bégin

Saint-Mandé, , France

Site Status WITHDRAWN

CHU St Etienne - Service des maladies infectieuses et tropicales

Saint-Priest-en-Jarez, , France

Site Status RECRUITING

Service des maladies respiratoires et infectieuses, CH de St Malo

St-Malo, , France

Site Status RECRUITING

Service des Maladies infectieuses et tropicales, Hôpital de Purpan, CHU de Toulouse

Toulouse, , France

Site Status RECRUITING

CHU Toulouse (Rangueil) Service de Cardiologie

Toulouse, , France

Site Status NOT_YET_RECRUITING

Service Universitaire des Maladies Infectieuses et du voyageur, CH de Tourcoing

Tourcoing, , France

Site Status RECRUITING

Service de Médecine interne et maladies infectieuses, Hôpital Bretonneau, CHU de Tours

Tours, , France

Site Status RECRUITING

Service de Maladies infectieuses et tropicales, Hôpitaux de Brabois, CHU de Nancy

Vandœuvre-lès-Nancy, , France

Site Status RECRUITING

Consultation de Médecine Interne, maladies infectieuses et tropicales, CH intercommunal de Villeneuve St Georges

Villeneuve-Saint-Georges, , France

Site Status RECRUITING

Médipôle Lyon Villeurbanne

Villeurbanne, , France

Site Status RECRUITING

Countries

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France

Central Contacts

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Louis BERNARD, MD, PHD

Role: CONTACT

Elodie MOUSSET

Role: CONTACT

02.47.47.46.65

Facility Contacts

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Jean-Phillipe LANOIX, Dr

Role: primary

03 22 66 88 13

DUBEE Vincent, Dr

Role: primary

06 65 80 70 22

Catherine CHIROUZE, Pr

Role: primary

03 22 66 88 13

Fabrice CAMOU, Dr

Role: primary

05 56 79 58 30

Elisabeth ROUVEIX NORDON, Pr

Role: primary

01 49 09 56 45

François DELAHAYE, Pr

Role: primary

04 72 35 76 28

Renaud VERDON, Pr

Role: primary

02 31 06 47 14

Emmanuel FORESTIER, Dr

Role: primary

04 79 96 58 47

Magali VIDAL, Dr

Role: primary

04 73 75 44 05

LEPEULE Raphael, Dr

Role: primary

01 49 81 22 11

Lionel PIROTH, Pr

Role: primary

03 80 29 36 31

Xavier LEMAIRE

Role: primary

03 27 94 74 50

Aurélien DINH, Dr

Role: primary

01 47 10 44 32

Thomas GUIMARD, Dr

Role: primary

02 51 44 63 85

Olivier EPAULARD, Pr

Role: primary

04 76 76 52 91

Hikombo HITOTO

Role: primary

02 43 43 26 14

Karine FAURE, Pr

Role: primary

03 20 44 57 43

Franck SIBELLAS, Dr

Role: primary

04 72 20 28 00

David BOUTOILLE, Pr

Role: primary

02 40 08 33 55

Elisa DEMONCHY, Dr

Role: primary

04 92 03 54 61

Simon SUNDER, Dr

Role: primary

05 49 78 30 75

Catherine LECHICHE, Dr

Role: primary

04 66 68 41 49

Laurent HOCQUELOUX, Dr

Role: primary

02 38 22 95 88

KRAUSE Jessica, Dr

Role: primary

Jean-Luc MAINARDI, Pr

Role: primary

01 56 09 22 54

Caroline CHARLIER, Dr

Role: primary

01 44 49 52 62

Xavier Marie DUVAL, Dr

Role: primary

01 40 25 88 92

RICHAUD Clémence, Dr

Role: primary

01 56 61 67 70

Guillaume BERAUD, Dr

Role: primary

05 49 44 40 04

Virginie VITRAT, Dr

Role: primary

04 50 63 66 02

Lydie KHATCHATOURIAN, Dr

Role: primary

02 90 94 41 12

Firouzé BANI SADR, Pr

Role: primary

03 26 78 71 89

Pierre TATTEVIN, Pr

Role: primary

02 99 28 95 64

Claire CHAPUZET, Dr

Role: primary

02 32 88 87 39

Elisabeth BOTELHO NEVERS, Dr

Role: primary

04 77 12 77 89

Mathieu DUPONT, Dr

Role: primary

02 99 21 21 70

Lydie PORTE, Dr

Role: primary

05 61 77 91 17

PORTE Lydie, Dr

Role: primary

Eric SENNEVILLE, Pr

Role: primary

03 20 69 48 48

Louis BERNARD, Pr

Role: primary

02 18 37 06 44

François GOEHRINGER, Dr

Role: primary

03 83 15 40 98

Olivier PATEY, Dr

Role: primary

01 43 86 20 81

Bertrand ISSARTEL, Dr

Role: primary

08 26 10 12 01

References

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Lemaignen A, Bernard L, Tattevin P, Bru JP, Duval X, Hoen B, Brunet-Houdard S, Mainardi JL, Caille A; RODEO (Relais Oral Dans le traitement des Endocardites a staphylocoques ou streptOcoques) and AEPEI (Association pour l'Etude et la Prevention de l'Endocardite Infectieuse) study groups. 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. BMJ Open. 2020 Jul 14;10(7):e033540. doi: 10.1136/bmjopen-2019-033540.

Reference Type DERIVED
PMID: 32665381 (View on PubMed)

Other Identifiers

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RODEO 1

Identifier Type: -

Identifier Source: org_study_id

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