Clinical trial NCT05394298: Short vs Long of Usual Treatment for Non Complicated Enterococcal Bacteremia
Official title: Randomized Non-inferiority Clinical Trial to Evaluate the Effectiveness and Security of Therapy for Non Complicated Enterococcal Bacteremia.
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Enterococcal Bacteremia
Keywords: Enterococcus
Bacteremia
Lead sponsor: Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Sponsor class: OTHER
Collaborators: name: Spanish Network for Research in Infectious Diseases
name: Spanish Clinical Research Network - SCReN
First posted: 2022-05-27
Enrollment: 284
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Randomised, multicentre, phase IV open trial of real clinical practice
Primary purpose: TREATMENT

Brief summary: Randomized clinical trial to determine the optimal duration of antibiotic treatment for E. Faecalis or E. faecium bacteraemia, following an innovative DOOR / RADAR (Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR)) analysis methodology.

Phase IV clinical trial, open-labelled, randomized, pragmatic, multicenter study to demonstrate non-inferiority of a 7-day antibiotic regimen vs. 14 days in the treatment of bacteremia due to E. faecalis or E. faecium.

Detailed description: Phase IV clinical trial, open-labelled, randomized, pragmatic, multicenter study to demonstrate non-inferiority of a 7-day antibiotic regimen vs. 14 days in the treatment of bacteremia due to E. faecalis or E. faecium.

Adequate antibiotic regimen is included in the protocol; initially this regimen included ciprofloxacine but this has been modified si that in the last version 3 dated feb 6th ciprofloxacine is not allowed as a possible treatment for these patients.

Antibiotic regimen included as possible treatments in the study are the follows:

* Isolated strains sensitive to ampicillin: ampicillin 2g/6 or 8h (i.v)
* Strains resistant to ampicillin and/or patients with allergy to beta-lactam drugs:
* Vancomycin: 15 mg/kg/12h i.v (with determination of trough plasma levels on day 2-3 of treatment if available).
* Linezolid: 600 mg/12 hours (i.v)
* Daptomycin: 8-10 mg/kg/day (i.v).

Intra-abdominal or soft tissue infections meeting study criteria, for which a polymicrobial infection is suspected:

Amoxicillin/clavulanic acid (isolates sensitive to ampicillin) 1 g/8h iv - Piperacillin/tazobactam (isolates sensitive to ampicillin) 4 g/8h (i.v.) - Combination of vancomycin, linezolid or daptomycin with a drug active against Gram-negative and anaerobic bacteria to ensure complete coverage in the case of bacteremia with a presumably polymicrobial focus.

Oral Treatment: In order to facilitate discharge of patients in both arms and reduce the risk of complications, as well as in keeping with the increasing use of this practice, the option to switch to oral therapy is allowed at the discretion of the responsible clinician, in both arms in patients with hemodynamic stability who tolerate oral treatment, at the discretion of the physician.

responsable.

- Amoxicillin 1g/8h or amoxicillin/clavulanic acid 875/125mg/8h if polymicrobial infection is suspected Linezolid 600mg/12h The choice will be in this order, according to the sensitivity of the isolate and allergies or other common circumstances for the use of these drugs.

The previous version allowed the use of cipro at the discretion of the clinicians as a sequential treatment option based on the fact that it is a clinical trial for low-risk bacteraemias in order to facilitate early sequential treatment (and thus avoid unnecessarily prolonging the hospital admissions.We decided to withdraw it on the basis that currently the EUCAST breakpoints only apply to urinary tract infections.The direct consequence is that the number of sequential treatment options is reduced.

Eligibility criteria: Inclusion Criteria:

* Adult patients (18 years of age or older) hospitalised with monomicrobial E. faecalis or E. faecium bacteremia.
* Negative follow-up blood cultures performed between days 2 and 3 of active treatment.
* Disappearance of fever (\>37.8ºC) within the first 72 hours.
* Signed informed consent.

The previous version allowed this inclusion criterion "Early adequate control of the source of bacteremia within 72 hours in the cases in which it is feasible and necessary (urinary or biliary tract release; abscess drainage; catheter-removal, etc)", which is now removed because it is already an exclusion criterion.

Exclusion Criteria:

* patients with polymicrobial bacteremia
* Patients with limited life expectancy in whom only conservative clinical management had been decided.
* Hemodynamic instability on day 5-6 after the start of active treatment.
* Patients wearing endovascular devices or prosthetic heart valves.
* Source of uncontrolled bacteremia adequately defined as undrained abscess, bile duct infection associated with plastic prostheses not removed or not replaced within the first 72 hours of bacteraemia, other infections related to non-removed prostheses, prostatitis, and infective endocarditis, as well as infections that require prolonged treatment, such as joint and bone infections.
* Existence of a secondary focus, different from the initial one, or presence of metastatic focus of infection.
* Severe neutropenia (\<500 cells / mm3) at the time of bacteremia diagnosis.
* Pregnancy and lactation.

Primary outcomes:
measure: Clinical success
timeFrame: TOC (Test of cure) visit (performed at day 28-32 after the end of suitable antibiotic treatment) or if drainage occurs after day 7 of treatment, TOC is to be done 7 days after that day.
Secondary outcomes:
measure: Rates of relapse or infective endocarditis diagnosis
timeFrame: TOC visit (day 28-32 ) and follow-up visit at day 90
measure: Survival
timeFrame: TOC visit (day 28-32) and follow-up visit at day 90
measure: Length of hospital stay
timeFrame: From patient first day inhospital (day of admission) until patient hospital discharge due to cure or home follow up assessed up to 30 days of the initiation of antibiotic administration
measure: Duration of intravenous and total therapy
timeFrame: From date of randomization until the last follow up visit planned 30 days of the initiation of antibiotic administration
measure: Incidence of diarrhoea by C. difficile
timeFrame: From date of randomization until the last follow up visit planned 30 days of the initiation of antibiotic administration
measure: Number of participants with Adverse Events due to antibiotic treatment
timeFrame: From date of randomization until the last follow up visit planned 90 days of the initiation of antibiotic administration
measure: Incidence of secondary infections
timeFrame: TOC visit (on day 28-32) and follow-up visit at day 90
measure: Change in SOFA score (Sepsis related Organ Failure Assessment)
timeFrame: Visit 0 (baseline) and TOC visit (on day 28-32) and follow-up visit at day 90
Other outcomes:
Locations:
city: Coruña
country: Spain
facility: COMPLEJO Universitario de La Coruña
state: A Coruña
city: Almería
country: Spain
facility: Hospital Universitario Torrecárdenas
state: Almeria
city: Palma De Mallorca
country: Spain
facility: Hospital Universitario Son Espases
state: Baleares
city: Terrassa
country: Spain
facility: Hospital Universitario Mutua de Terrassa
state: Barcelona
city: Barakaldo
country: Spain
facility: Hospital de Cruces
state: Bizkaia
city: Jerez De La Frontera
country: Spain
facility: Hospital Universitario de Jerez de La Frontera
state: Cadiz
city: Puerto Real
country: Spain
facility: Hospital Universitario de Puerto Real
state: Cadiz
city: Jaén
country: Spain
facility: Hospital Universitario de Jaén
state: Jaen
city: Marbella
country: Spain
facility: Hospital Universitario Costa Del Sol
state: Malaga
city: Málaga
country: Spain
facility: Hospital Universitario Regional de Málaga
state: Malaga
city: Vigo
country: Spain
facility: Hospital Universitario de Vigo
state: Pontevedra
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Granada
country: Spain
facility: Hospital Universitario Virgen de Las Nieves
city: Huelva
country: Spain
facility: Hospital Universitario Juan Ramón Jiménez
city: Madrid
country: Spain
facility: Hospital Universitario Ramón y Cajal
city: Murcia
country: Spain
facility: Complejo Hospitalario Universitario Virgen de la Arrixaca
city: San Sebastián
country: Spain
facility: Hospital Universitario de Donostia
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Macarena
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen Del Rocío
city: Sevilla
country: Spain
facility: Hospital Universitario Virgen de Valme
Study officials:
affiliation: Hospital Universitario Virgen Macarena
name: Luis Eduardo López Cortés
role: PRINCIPAL_INVESTIGATOR
References: