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Ampicillin and Ceftriaxone for the Treatment of Enterococcus Faecalis Infective Endocarditis.

Phase 4
Not yet recruiting
Conditions
Endocarditis, Infective
Interventions
Drug: Control regimen
Drug: Experimental regimen
Registration Number
NCT06423898
Lead Sponsor
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Brief Summary

Phase IV, open-label, randomized and multicenter clinical trial to prove that patients with Enterococcus faecalis infective endocarditis treated with an antibiotic treatment as a continuous infusion is non-inferior to the standard intermittent infusion regimen, usually administered in hospitalized patients.

Detailed Description

The aim of the study is to prove that the continuous infusion of antibiotic treatment for the patients with Enterococcus faecalis infective endocarditis is as effective and safe as the traditional intermittent infusion. The continuous infusion modality of treatment is expected to provide numerous benefits for individual patients, global health, and for the National Health Care System by reducing to hospital stays from 4-6 weeks to approximately 2-3 weeks and hospital-driven complications.

The mortality, rate of serious adverse events, total number of days of antibiotic treatment and days of hospitalization, among others, are included as secondary objectives.

This is a pragmatic study as the number or visits performed for the study are similar to the normal clinical follow-up for this patients. Final contact and final visit for the study will be performed at 365 days after the 42 days of treatment.

Recruitment & Eligibility

Status
NOT_YET_RECRUITING
Sex
All
Target Recruitment
284
Inclusion Criteria
  • Adult patients
  • Possible or definitive diagnosis of infective endocarditis due to Enterococcus faecalis
  • Signed informed consent of patients
Exclusion Criteria
  • Allergy to penicillins or cephalosporins
  • Pregnancy and lactation
  • Polymicrobial infection including microorganisms different to E. faecalis

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Intermittent intravenous antibiotic infusionControl regimenAmpicillin 2g/4h plus ceftriaxone 2g/12h intermittent infusion. The duration of treatment will be 42 days.
Continuous intravenous antibiotic infusionExperimental regimenAmpicillin 2g/4h plus ceftriaxone 2g/12h intermittently infused. The duration of treatment will be 42 days.
Primary Outcome Measures
NameTimeMethod
Clinical failureOne year after the end of the treatment

It is defined as follow:

i) Confirmed recurrence of E. faecalis infective endocarditis, ii) all-cause mortality. A composite primary endpoint has been chosen to include both a very clinically relevant variable and a hard variable such as survival

Secondary Outcome Measures
NameTimeMethod
Antibiotic treatment daysUp to 12 months after treatment administration

Number of antibiotic treatment days

Minimum Inhibitory ConcentrationDay 14

Minimum Inhibitory Concentration of ampicillin induced by ceftriaxone in the strains responsible for recurrences and control strains

Cardiac surgeriesUp to 12 months after treatment administration

Number of unplanned cardiac surgeries

RecurrenceUp to 12 months after treatment administration

Number of recurrence of Enterococcus faecalis infective endocarditis

Minimum free serum concentrationDay 14

Minimum free serum concentration of antibiotics used

Therapeutic failureUp to 12 months after treatment administration

Number of deaths

ReadmissionsUp to 12 months after treatment administration

Number of unplanned readmissions

Treatment switching42 days

Number of patient of treatment switching

Serious adverse eventsFrom randomisation until 30 days after the last dose administration

Number of medication-related adverse events

Outpatient Parenteral Antimicrobial TherapyUp to 12 months after treatment administration

Number of Outpatient Parenteral Antimicrobial Therapy

Healthcare-associated infectionsUp to 12 months after treatment administration

Number of healthcare-associated infections

Steady-state plasma concentrationDay 14

Steady-state plasma concentration of antibiotics used

Pharmacokinetic parametersDay 14

Volume of distribution, clearance, elimination constant of antibiotics used

Trial Locations

Locations (17)

Hospital Universitario de Cruces

🇪🇸

Barakaldo, Spain

Hospital Universitario Vall d'Hebron

🇪🇸

Barcelona, Spain

Hospital Universitario Virgen de las Nieves

🇪🇸

Granada, Spain

Hospital Clínico de Barcelona

🇪🇸

Barcelona, Spain

Hospital Universitario de Donostia

🇪🇸

Donostia, Spain

Hospital Universitario de Canarias

🇪🇸

La Laguna, Spain

Hospital San Pedro

🇪🇸

Logroño, Spain

Hospital Universitario Puerta del Hierro

🇪🇸

Madrid, Spain

Hospital Universitario Marqués de Valdecilla

🇪🇸

Santander, Spain

Hospital Universitari MútuaTerrassa

🇪🇸

Terrassa, Spain

Hospital Universitario de Álava

🇪🇸

Alava, Spain

Hospital Universitario Gregorio Marañón

🇪🇸

Madrid, Spain

Hospital Universitario La Paz

🇪🇸

Madrid, Spain

Hospital Universitario Virgen de la Victoria

🇪🇸

Málaga, Spain

Hospital Universitario Regional de Málaga

🇪🇸

Málaga, Spain

Hospital Universitario Virgen Macarena

🇪🇸

Sevilla, Spain

Hospital Universitario Virgen del Rocío

🇪🇸

Sevilla, Spain

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