Endocarditis, InfectivePhase 4DOBLEINCT06423898
Ampicillin and Ceftriaxone for the Treatment of Enterococcus Faecalis Infective Endocarditis.
A Phase 4 study testing Ampicillin plus ceftriaxone in continuous infusion and Ampicillin plus ceftriaxone in intermittent infusion of 14 days, after which the treatment may be changed in people with Endocarditis, Infective, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 18 sites in Spain.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Endocarditis, Infective
- What is being tested?
- Ampicillin plus ceftriaxone in continuous infusion and Ampicillin plus ceftriaxone in intermittent infusion of 14 days, after which the treatment may be changed
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 284 participants
- Where
- 18 sitesSpain
- Study dates
- 9 Oct 2024to 31 Dec 2028
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients
- Possible or definitive diagnosis of infective endocarditis due to Enterococcus faecalis
- Signed informed consent of patients
Who cannot join
- Allergy to penicillins or cephalosporins
- Pregnancy and lactation
- Polymicrobial infection including microorganisms different to E. faecalis
Trial locations and contacts
18 sites in 1 country. Contact the study team or a site near you to ask about taking part.
18 sites in 1 country
Spain18 sites, 8 recruiting
- Recruiting
Hospital Universitario de Álava
Alava, 01009
Juan Carlos Gainzarain, MD, juancarlos.gainzarainarana@osakidetza.eus
- Active, not recruiting
Hospital Universitario de Cruces
Barakaldo, 48903
- Not yet recruiting
Hospital Universitario Vall d'Hebron
Barcelona, 08035
Nuria Fernández Hidalgo, MD, nufernan@gmail.com
- Not yet recruiting
Hospital Clínico de Barcelona
Barcelona, 08036
Guillermo Cuervo Requena, MD, glcuervo@clinic.cat
- Active, not recruiting
Hospital Universitario de Donostia
Donostia / San Sebastian, 20014
- Active, not recruiting
Hospital Universitario Virgen de las Nieves
Granada, 18014
- Active, not recruiting
Hospital San Pedro
Logroño, 26006
- Active, not recruiting
Hospital Universitario Gregorio Marañón
Madrid, 28007
- Not yet recruiting
Hospital Clínico San Carlos
Madrid, 28040
Ana Muñoz Gómez, MD, amg.sevilla@gmail.com
- Not yet recruiting
Hospital Universitario La Paz
Madrid, 28046
Belén Loeches, MD, bloeches@yahoo.es
- Active, not recruiting
Hospital Universitario Puerta del Hierro
Madrid, 28222
- Active, not recruiting
Hospital Universitario Regional de Málaga
Málaga, 29010
- Active, not recruiting
Hospital Universitario Virgen de la Victoria
Málaga, 29010
- Recruiting
Hospital Universitario de Canarias
San Cristóbal de La Laguna, 38320
Remedios Alemán, MD, remealeman@hotmail.com
- Recruiting
Hospital Universitario Marqués de Valdecilla
Santander, 39008
Mª Carmen Fariñas, MD, mcarmen.farinas@scsalud.es
MD
- Active, not recruiting
Hospital Universitario Virgen Macarena
Seville, 41009
- Recruiting
Hospital Universitario Virgen del Rocío
Seville, 41013
Cesar Aristides de Alarcon gonzalez, MD, +34 955 013414, aa2406ge@yahoo.es
- Active, not recruiting
Hospital Universitari MútuaTerrassa
Terrassa, 08221
About this study
Official title: Efficacy and Safety of Ampicillin and Ceftriaxone Continuous Infusion Versus Standard Therapy for the Treatment of Enterococcus Faecalis Infective Endocarditis (DOβLEI Study)
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.
Read the 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.
- Conditions
- Endocarditis, Infective
- Being tested
- Ampicillin plus ceftriaxone in continuous infusion, Ampicillin plus ceftriaxone in intermittent infusion of 14 days, after which the treatment may be changed
- Keywords
- Endocarditis, Infective, Enterococcus faecalis, Antibiotics, Outpatient Infusion Therapies, Outpatient Care
- Medical subject headings
- Endocarditis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ampicillin plus ceftriaxone in continuous infusionDrug
Also called Experimental regimen
Continuous intravenous antibiotic infusion during 42 days for Infective Endocarditis
Ampicillin plus ceftriaxone in intermittent infusion of 14 days, after which the treatment may be changedDrug
Also called Control regimen
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:
- Intravenous treatment according to the following regimens: Ampicillin plus ceftriaxone as an intermittent infusion, teicoplanin, daptomycin, dalbavancin or linezolid.
- Oral treatment according to the following regimens: amoxicillin plus moxifloxacin, amoxicillin plus linezolid, amoxicillin plus rifampin, linezolid plus moxifloxacin or linezolid plus rifampin.
| Study group | Role | What they receive |
|---|---|---|
| Continuous intravenous antibiotic infusion | Experimental | Ampicillin 12g/24h plus ceftriaxone 4g/12h continuous infusion. The duration of treatment will be 42 days. Receives: 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 Receives: Drug: Ampicillin plus ceftriaxone in intermittent infusion of 14 days, after which the treatment may be changed |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical failure
It is defined as follow:
- 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
Measured: One year after the end of the treatment
Secondary outcomes (12)
Therapeutic failure
Number of deaths
Measured: Up to 12 months after treatment administration
Cardiac surgeries
Number of unplanned cardiac surgeries
Measured: Up to 12 months after treatment administration
Readmissions
Number of unplanned readmissions
Measured: Up to 12 months after treatment administration
Adverse events
Number of medication-related adverse events
Measured: From randomisation until 30 days after the last dose administration
Antibiotic treatment days
Number of antibiotic treatment days
Measured: Up to 12 months after treatment administration
Outpatient Parenteral Antimicrobial Therapy
Number of Outpatient Parenteral Antimicrobial Therapy
Measured: Up to 12 months after treatment administration
Healthcare-associated infections
Number of healthcare-associated infections
Measured: Up to 12 months after treatment administration
Recurrence
Number of recurrence of Enterococcus faecalis infective endocarditis
Measured: Up to 12 months after treatment administration
Minimum free serum concentration
Minimum free serum concentration of antibiotics used
Measured: Day 14
Steady-state plasma concentration
Steady-state plasma concentration of antibiotics used
Measured: Day 14
Pharmacokinetic parameters
Volume of distribution, clearance, elimination constant of antibiotics used
Measured: Day 14
Minimum Inhibitory Concentration
Minimum Inhibitory Concentration of ampicillin induced by ceftriaxone in the strains responsible for recurrences and control strains
Measured: Day 14
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2024
- Study start9 Oct 2024
- Primary completion31 Jul 2027 (estimated)
- Study completion31 Dec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Endocarditis, InfectiveStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Parallel Assignment Randomized 1:1 to experimental group (continuous infusion arm) or control group (intermittent infusion arm)
- Masking
- None (open label)
- Enrolment
- 284 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
- Sponsor type
- University, hospital or other
- Collaborators
- Spanish Clinical Research Network - SCReN
- Responsible party
- Sponsor
- Investigators
- HUVR Cesar Arístides de Alarcón González, MD-PhD, Principal investigator, Fundación para la Gestión de la Investigación en Salud de Sevilla
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06423898
- Sponsor's protocol ID
- DOBLEI
- Acronym
- DOBLEI
- Status last verified
- Jul 2025
- First submitted
- 13 May 2024
- Last updated
- 25 Jul 2025
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: The results will be shared with the investigators involved in the study, and will be shared when the analysis of the results is performed.
Study at a glance
From the registry record, last updated by the sponsor on 25 Jul 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Efficacy and Safety of Ampicillin and Ceftriaxone Continuous Infusion Versus Standard Therapy for the Treatment of Enterococcus Faecalis Infective Endocarditis (DOβLEI Study)
- ClinicalTrials.gov ID
- NCT06423898
- Acronym / sponsor ID
- DOBLEI / DOBLEI
- Conditions
- Endocarditis, Infective
- Keywords
- Endocarditis, Infective, Enterococcus faecalis, Antibiotics, Outpatient Infusion Therapies, Outpatient Care
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 284 participants (estimated)
- Lead sponsor
- Fundación Pública Andaluza para la gestión de la Investigación en SevillaUniversity, hospital or other
- Collaborators
- Spanish Clinical Research Network - SCReN
- Study start
- 9 Oct 2024 (actual)
- Primary completion
- 31 Jul 2027 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 21 May 2024 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Parallel Assignment Randomized 1:1 to experimental group (continuous infusion arm) or control group (intermittent infusion arm)
| Arm | Type | Receives |
|---|---|---|
| Continuous intravenous antibiotic infusion | Experimental | Drug: Ampicillin plus ceftriaxone in continuous infusionAmpicillin 12g/24h plus ceftriaxone 4g/12h continuous infusion. The duration of treatment will be 42 days. |
| Standard treatment | Active comparator | Drug: Ampicillin plus ceftriaxone in intermittent infusion of 14 days, after which the treatment may be changedAmpicillin 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Adult patients
- Possible or definitive diagnosis of infective endocarditis due to Enterococcus faecalis
- Signed informed consent of patients
Key exclusion criteria (3 listed)
- Allergy to penicillins or cephalosporins
- Pregnancy and lactation
- Polymicrobial infection including microorganisms different to E. faecalis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Ampicillin plus ceftriaxone in continuous infusionAlso: Experimental regimenContinuous intravenous antibiotic infusion during 42 days for Infective Endocarditis | Drug | Continuous intravenous antibiotic infusion |
| Ampicillin plus ceftriaxone in intermittent infusion of 14 days, after which the treatment may be changedAlso: Control regimenAmpicillin 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. | Drug | Standard treatment |
Primary outcome
Clinical failure
Time frame: 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
12 secondary outcomes
Therapeutic failure
Time frame: Up to 12 months after treatment administration
Cardiac surgeries
Time frame: Up to 12 months after treatment administration
Readmissions
Time frame: Up to 12 months after treatment administration
Adverse events
Time frame: From randomisation until 30 days after the last dose administration
Antibiotic treatment days
Time frame: Up to 12 months after treatment administration
Outpatient Parenteral Antimicrobial Therapy
Time frame: Up to 12 months after treatment administration
Healthcare-associated infections
Time frame: Up to 12 months after treatment administration
Recurrence
Time frame: Up to 12 months after treatment administration
Minimum free serum concentration
Time frame: Day 14
Steady-state plasma concentration
Time frame: Day 14
Pharmacokinetic parameters
Time frame: Day 14
Minimum Inhibitory Concentration
Time frame: Day 14
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Jul 2025.
- Individual participant dataSharing planned: Yes. The results will be shared with the investigators involved in the study, and will be shared when the analysis of the results is performed.
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CBCT vs OPT on the Oral Health Status at 12 Months of Patients Hospitalized for Infective Endocarditis.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
HUVR Cesar Arístides de Alarcón González, MD-PhD principal investigator
Fundación para la Gestión de la Investigación en Salud de Sevilla
18 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Ampicillin plus ceftriaxone in continuous infusion and Ampicillin plus ceftriaxone in intermittent infusion of 14 days, after which the treatment may be changed in people with Endocarditis, Infective, run by Fundación Pública Andaluza para la gestión de la Investigación en Sevilla at 18 sites in Spain.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 25 Jul 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 18 sites in Spain. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Laura Herrera Hidalgo, MD-PhD (+34955013414, lauraherrerahidalgo@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical failure (time frame: One year after the end of the treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Jul 2025.