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

NCT06423898 | Recruiting Phase 4

• 1 other identifier: DOBLEI
• Study Type: interventional
• Target: 284
• Locations: 1 country
• Sites: 18

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.

Conditions

Endocarditis, Infective

Keywords

Endocarditis, Infective; Enterococcus faecalis; Antibiotics; Outpatient Infusion Therapies; Outpatient Care

Outcome Measures

Primary Outcomes (1)

• Clinical failure

  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

  One year after the end of the treatment

Secondary Outcomes (12)

• Therapeutic failure

  Up to 12 months after treatment administration

• Cardiac surgeries

  Up to 12 months after treatment administration

• Readmissions

  Up to 12 months after treatment administration

• Adverse events

  From randomisation until 30 days after the last dose administration

• Antibiotic treatment days

  Up to 12 months after treatment administration

Study Arms (2)

Continuous intravenous antibiotic infusion

EXPERIMENTAL

Ampicillin 12g/24h plus ceftriaxone 4g/12h continuous infusion. The duration of treatment will be 42 days.

Drug: Ampicillin plus ceftriaxone in continuous infusion

Standard treatment

ACTIVE COMPARATOR

Ampicillin 2g/4h plus ceftriaxone 2g/12h intermittent infusion for a minimum of 14 days. Starting on day 14 of treatment, if the patient is discharged from the hospital, the following treatments will be permitted: 1. Intravenous treatment in TADE programs according to the following regimens: 1. Ampicillin 2g/4h plus ceftriaxone 2g/12h as an intermittent infusion 2. Teicoplanin 10-12mg/kg/24h 3. Daptomycin 10-12mg/kg/24h 4. Dalbavancin: Initial dose: 2 doses of 1500mg every 2 weeks. Maintenance dose: 1500mg every 15days. 5. Linezolid: 600mg/12hours 2. Oral treatment according to the following regimens: 1. Amoxicillin 1 g/6h + Moxifloxacin 400mg/24h. 2. Amoxicillin 1 g/6h + Linezolid 600 mg/12h. 3. Amoxicillin 1 g/6h + Rifampin 600 mg/12h. 4. Linezolid 600 mg/12h + Moxifloxacin 400mg/24h. 5. Linezolid 600 mg/12h + Rifampin 600 mg/12h. The duration of treatment will be 42 days

Drug: Ampicillin plus ceftriaxone in intermittent infusion of 14 days, after which the treatment may be changed

Interventions

Ampicillin plus ceftriaxone in continuous infusion DRUG

Continuous intravenous antibiotic infusion during 42 days for Infective Endocarditis

Also known as: Experimental regimen

Continuous intravenous antibiotic infusion

Ampicillin plus ceftriaxone in intermittent infusion of 14 days, after which the treatment may be changed DRUG

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.

Also known as: Control regimen

Standard treatment

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients
• Possible or definitive diagnosis of infective endocarditis due to Enterococcus faecalis
• Signed informed consent of patients

You may not qualify if:

• Allergy to penicillins or cephalosporins
• Pregnancy and lactation
• Polymicrobial infection including microorganisms different to E. faecalis

Sponsors & Collaborators

• Fundación Pública Andaluza para la gestión de la Investigación en Sevilla: lead
• Spanish Clinical Research Network - SCReN: collaborator

Study Sites (18)

Hospital Universitario de Álava

Alava, 01009, Spain

RECRUITING

Hospital Universitario de Cruces

Barakaldo, 48903, Spain

ACTIVE NOT RECRUITING

Hospital Universitario Vall d'Hebron

Barcelona, 08035, Spain

NOT YET RECRUITING

Hospital Clínico de Barcelona

Barcelona, 08036, Spain

NOT YET RECRUITING

Hospital Universitario de Donostia

Donostia / San Sebastian, 20014, Spain

ACTIVE NOT RECRUITING

Hospital Universitario Virgen de las Nieves

Granada, 18014, Spain

ACTIVE NOT RECRUITING

Hospital San Pedro

Logroño, 26006, Spain

ACTIVE NOT RECRUITING

Hospital Universitario Gregorio Marañón

Madrid, 28007, Spain

ACTIVE NOT RECRUITING

Hospital Clínico San Carlos

Madrid, 28040, Spain

NOT YET RECRUITING

Hospital Universitario La Paz

Madrid, 28046, Spain

NOT YET RECRUITING

Hospital Universitario Puerta del Hierro

Madrid, 28222, Spain

ACTIVE NOT RECRUITING

Hospital Universitario Regional de Málaga

Málaga, 29010, Spain

ACTIVE NOT RECRUITING

Hospital Universitario Virgen de la Victoria

Málaga, 29010, Spain

ACTIVE NOT RECRUITING

Hospital Universitario de Canarias

San Cristóbal de La Laguna, 38320, Spain

RECRUITING

Hospital Universitario Marqués de Valdecilla

Santander, 39008, Spain

RECRUITING

Hospital Universitario Virgen Macarena

Seville, 41009, Spain

ACTIVE NOT RECRUITING

Hospital Universitario Virgen del Rocío

Seville, 41013, Spain

RECRUITING

Hospital Universitari MútuaTerrassa

Terrassa, 08221, Spain

ACTIVE NOT RECRUITING

MeSH Terms

Conditions

Endocarditis

Interventions

Ampicillin; Ceftriaxone

Condition Hierarchy (Ancestors)

Heart Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Penicillin G; Penicillins; beta-Lactams; Lactams; Amides; Organic Chemicals; Sulfur Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cefotaxime; Cephacetrile; Cephalosporins; Thiazines

Study Officials

• HUVR Cesar Arístides de Alarcón González, MD-PhD

  Fundación para la Gestión de la Investigación en Salud de Sevilla

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Laura Herrera Hidalgo, MD-PhD

CONTACT

+34955013414; lauraherrerahidalgo@gmail.com

Clara M Rosso Fernández, MD-PhD

CONTACT

+34955013414; claram.rosso.sspa@juntadeandalucia.es

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Parallel Assignment Randomized 1:1 to experimental group (continuous infusion arm) or control group (intermittent infusion arm)

Study Record Dates

• First Submitted: May 13, 2024
• First Posted: May 21, 2024
• Study Start: October 9, 2024
• Primary Completion (Estimated): July 31, 2027
• Study Completion (Estimated): December 31, 2028
• Last Updated: July 25, 2025

Record last verified: 2025-07

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: 6 months
• Access Criteria: Direct collaborators within the study

Locations

ES (18)