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

Phase 4

Recruiting

• Conditions: Endocarditis, Infective
• Interventions: Drug: Ampicillin plus ceftriaxone in continuous infusion; Drug: Ampicillin plus ceftriaxone in intermittent infusion of 14 days, after which the treatment may be changed

• 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 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.

Study Timeline

• Study First Submitted: 2024-05-13
• Study First Submitted QC: 2024-05-16
• Study First Posted: 2024-05-21
• Study Start: 2024-10-09
• Status Verified: 2025-07
• Last Update Submitted: 2025-07-24
• Last Update Posted: 2025-07-25
• Primary Completion: 2027-07-31
• Study Completion: 2028-12-31

Recruitment & Eligibility

• Status: 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

Group	Intervention	Description
Continuous intravenous antibiotic infusion	Ampicillin plus ceftriaxone in continuous infusion	Ampicillin 12g/24h plus ceftriaxone 4g/12h continuous infusion. The duration of treatment will be 42 days.
Standard treatment	Ampicillin plus ceftriaxone in intermittent infusion of 14 days, after which the treatment may be changed	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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
Therapeutic failure	Up to 12 months after treatment administration	Number of deaths
Cardiac surgeries	Up to 12 months after treatment administration	Number of unplanned cardiac surgeries
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
Healthcare-associated infections	Up to 12 months after treatment administration	Number of healthcare-associated infections
Recurrence	Up to 12 months after treatment administration	Number of recurrence of Enterococcus faecalis infective endocarditis
Pharmacokinetic parameters	Day 14	Volume of distribution, clearance, elimination constant of antibiotics used
Readmissions	Up to 12 months after treatment administration	Number of unplanned readmissions
Outpatient Parenteral Antimicrobial Therapy	Up to 12 months after treatment administration	Number of Outpatient Parenteral Antimicrobial Therapy
Minimum free serum concentration	Day 14	Minimum free serum concentration 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
Steady-state plasma concentration	Day 14	Steady-state plasma concentration of antibiotics used

Trial Locations

Locations (18)

Hospital Universitario de Álava; 🇪🇸 Alava, Spain

Hospital Universitario de Cruces; 🇪🇸 Barakaldo, Spain

Hospital Universitario Vall d'Hebron; 🇪🇸 Barcelona, Spain

Hospital Clínico de Barcelona; 🇪🇸 Barcelona, Spain

Hospital Universitario de Donostia; 🇪🇸 Donostia, Spain

Hospital Universitario Virgen de las Nieves; 🇪🇸 Granada, Spain

Hospital Universitario de Canarias; 🇪🇸 La Laguna, Spain

Hospital San Pedro; 🇪🇸 Logroño, Spain

Hospital Universitario Gregorio Marañón; 🇪🇸 Madrid, Spain

Hospital Clínico San Carlos; 🇪🇸 Madrid, Spain

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