Endocarditis, Infective
Conditions
Keywords
Endocarditis, Infective, Enterococcus faecalis, Antibiotics, Outpatient Infusion Therapies, Outpatient Care
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 treatment, 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 standard treatment. 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.
Interventions
DRUGAmpicillin plus ceftriaxone in continuous infusion
Continuous intravenous antibiotic infusion during 42 days for Infective Endocarditis
DRUGAmpicillin plus ceftriaxone in intermittent infusion of 14 days, after which the treatment may be changed
Ampicillin plus ceftriaxone as an intermittent infusion for a minimum of 14 days. After, if the patient is discharged from the hospital, the following treatments, until the 42-day treatment period is completed: 1. Intravenous treatment according to the following regimens: Ampicillin plus ceftriaxone as an intermittent infusion, teicoplanin, daptomycin, dalbavancin or linezolid. 2. Oral treatment according to the following regimens: amoxicillin plus moxifloxacin, amoxicillin plus linezolid, amoxicillin plus rifampin, linezolid plus moxifloxacin or linezolid plus rifampin.
Sponsors
Spanish Clinical Research Network - SCReN
Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
Parallel Assignment Randomized 1:1 to experimental group (continuous infusion arm) or control group (intermittent infusion arm)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical failure | One 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
| Measure | Time frame | Description |
|---|---|---|
| Cardiac surgeries | Up to 12 months after treatment administration | Number of unplanned cardiac surgeries |
| Readmissions | Up to 12 months after treatment administration | Number of unplanned readmissions |
| Adverse events | From randomisation until 30 days after the last dose administration | Number of medication-related adverse events |
| Antibiotic treatment days | Up to 12 months after treatment administration | Number of antibiotic treatment days |
| Outpatient Parenteral Antimicrobial Therapy | Up to 12 months after treatment administration | Number of Outpatient Parenteral Antimicrobial Therapy |
| Therapeutic failure | Up to 12 months after treatment administration | Number of deaths |
| Recurrence | Up to 12 months after treatment administration | Number of recurrence of Enterococcus faecalis infective endocarditis |
| Minimum free serum concentration | Day 14 | Minimum free serum concentration of antibiotics used |
| Steady-state plasma concentration | Day 14 | Steady-state plasma concentration of antibiotics used |
| Pharmacokinetic parameters | Day 14 | Volume of distribution, clearance, elimination constant of antibiotics used |
| Minimum Inhibitory Concentration | Day 14 | Minimum Inhibitory Concentration of ampicillin induced by ceftriaxone in the strains responsible for recurrences and control strains |
| Healthcare-associated infections | Up to 12 months after treatment administration | Number of healthcare-associated infections |
Countries
Spain
Contacts
Primary ContactLaura Herrera Hidalgo, MD-PhD
Backup ContactClara M Rosso Fernández, MD-PhD
Outcome results
None listed