## Protocol Section
### Identification Module
**NCT ID:** NCT06423898

**Acronym:** DOBLEI

**Brief Title:** Ampicillin and Ceftriaxone for the Treatment of Enterococcus Faecalis Infective Endocarditis.

**Official Title:** Efficacy and Safety of Ampicillin and Ceftriaxone Continuous Infusion Versus Intermittent Infusion for the Treatment of Enterococcus Faecalis Infective Endocarditis (DOBLEI)

#### Organization Study ID Info
**ID:** DOBLEI
#### Organization
**Class:** OTHER
**Full Name:** Fundación Pública Andaluza para la gestión de la Investigación en Sevilla
### Status Module
#### Completion Date
**Date:** 2028-12-31

**Type:** ESTIMATED

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2024-05-21

**Type:** ACTUAL

**Last Update Submit Date:** 2024-05-16

**Overall Status:** NOT_YET_RECRUITING

#### Primary Completion Date
**Date:** 2027-07-31

**Type:** ESTIMATED

#### Start Date
**Date:** 2024-09-30

**Type:** ESTIMATED

**Status Verified Date:** 2024-05

#### Study First Post Date
**Date:** 2024-05-21
**Type:** ACTUAL
**Study First Submit Date:** 2024-05-13
**Study First Submit QC Date:** 2024-05-16
### Sponsor Collaborators Module

#### Collaborators

**Class:** NETWORK

**Name:** Spanish Clinical Research Network - SCReN

#### Lead Sponsor

**Class:** OTHER

**Name:** Fundación Pública Andaluza para la gestión de la Investigación en Sevilla

#### Responsible Party

**Type:** SPONSOR

### Oversight Module

**Is FDA Regulated Device:** False

**Is FDA Regulated Drug:** False

**Oversight Has DMC:** False

### Description Module

**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.

### Conditions Module

**Conditions:**

- Endocarditis, Infective

**Keywords:**

- Endocarditis, Infective

- Enterococcus faecalis

- Antibiotics

- Outpatient Infusion Therapies

- Outpatient Care

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** PARALLEL

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

##### Masking Info

**Masking:** NONE

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 200

**Type:** ESTIMATED

**Phases:**

- PHASE4

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Description:** Ampicillin 2g/4h plus ceftriaxone 2g/12h intermittently infused. The duration of treatment will be 42 days.

**Intervention Names:**

- Drug: Experimental regimen

**Label:** Continuous intravenous antibiotic infusion

**Type:** EXPERIMENTAL

#### Arm Group 2

**Description:** Ampicillin 2g/4h plus ceftriaxone 2g/12h intermittent infusion. The duration of treatment will be 42 days.

**Intervention Names:**

- Drug: Control regimen

**Label:** Intermittent intravenous antibiotic infusion

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- Continuous intravenous antibiotic infusion

**Description:** Continuous intravenous antibiotic infusion during 42 days for Infective Endocarditis

**Name:** Experimental regimen

**Type:** DRUG

#### Intervention 2

**Arm Group Labels:**

- Intermittent intravenous antibiotic infusion

**Description:** Intermittent intravenous antibiotic infusion during 42 days for Infective Endocarditis

**Name:** Control regimen

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** 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

**Measure:** Clinical failure

**Time Frame:** One year after the end of the treatment

#### Secondary Outcomes

**Description:** Number of deaths

**Measure:** Therapeutic failure

**Time Frame:** Up to 12 months after treatment administration

**Description:** Number of patient of treatment switching

**Measure:** Treatment switching

**Time Frame:** 42 days

**Description:** Number of unplanned cardiac surgeries

**Measure:** Cardiac surgeries

**Time Frame:** Up to 12 months after treatment administration

**Description:** Number of unplanned readmissions

**Measure:** Readmissions

**Time Frame:** Up to 12 months after treatment administration

**Description:** Number of medication-related adverse events

**Measure:** Serious adverse events

**Time Frame:** From randomisation until 30 days after the last dose administration

**Description:** Number of antibiotic treatment days

**Measure:** Antibiotic treatment days

**Time Frame:** Up to 12 months after treatment administration

**Description:** Number of Outpatient Parenteral Antimicrobial Therapy

**Measure:** Outpatient Parenteral Antimicrobial Therapy

**Time Frame:** Up to 12 months after treatment administration

**Description:** Number of healthcare-associated infections

**Measure:** Healthcare-associated infections

**Time Frame:** Up to 12 months after treatment administration

**Description:** Number of recurrence of Enterococcus faecalis infective endocarditis

**Measure:** Recurrence

**Time Frame:** Up to 12 months after treatment administration

**Description:** Minimum free serum concentration of antibiotics used

**Measure:** Minimum free serum concentration

**Time Frame:** Day 14

**Description:** Steady-state plasma concentration of antibiotics used

**Measure:** Steady-state plasma concentration

**Time Frame:** Day 14

**Description:** Volume of distribution, clearance, elimination constant of antibiotics used

**Measure:** Pharmacokinetic parameters

**Time Frame:** Day 14

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

**Measure:** Minimum Inhibitory Concentration

**Time Frame:** Day 14

### Eligibility Module

**Eligibility Criteria:** 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

**Minimum Age:** 18 Years

**Sex:** ALL

**Standard Ages:**

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Central Contacts

**Contact 1:**

**Email:** lauraherrerahidalgo@gmail.com

**Name:** Laura Herrera Hidalgo, MD-PhD

**Phone:** +34955013414

**Role:** CONTACT

**Contact 2:**

**Email:** claram.rosso.sspa@juntadeandalucia.es

**Name:** Clara M Rosso Fernández, MD-PhD

**Phone:** +34955013414

**Role:** CONTACT

#### Locations

**Location 1:**

**City:** Alava

**Contacts:**

***Contact 1:***

- **Email:** juancarlos.gainzarainarana@osakidetza.eus

- **Name:** Juan Carlos Gainzarain, MD

- **Role:** CONTACT

**Country:** Spain

**Facility:** Hospital Universitario de Álava

**Zip:** 01009

**Location 2:**

**City:** Barakaldo

**Contacts:**

***Contact 1:***

- **Email:** goikoetxeaagirre@osakidetza.eus

- **Name:** Ane Josune Goikoetxea, MD

- **Role:** CONTACT

***Contact 2:***

- **Name:** MD

- **Role:** CONTACT

**Country:** Spain

**Facility:** Hospital Universitario de Cruces

**Zip:** 48903

**Location 3:**

**City:** Barcelona

**Contacts:**

***Contact 1:***

- **Email:** nufernan@gmail.com

- **Name:** Nuria Fernández Hidalgo, MD

- **Role:** CONTACT

**Country:** Spain

**Facility:** Hospital Universitario Vall d'Hebron

**Zip:** 08035

**Location 4:**

**City:** Barcelona

**Contacts:**

***Contact 1:***

- **Email:** glcuervo@clinic.cat

- **Name:** Guillermo Cuervo Requena, MD

- **Role:** CONTACT

**Country:** Spain

**Facility:** Hospital Clínico de Barcelona

**Zip:** 08036

**Location 5:**

**City:** Donostia

**Contacts:**

***Contact 1:***

- **Email:** muskilda.goyenechedelrio@osakidetza.eus

- **Name:** Muskildav Goyeneche del Rio, MD

- **Role:** CONTACT

**Country:** Spain

**Facility:** Hospital Universitario de Donostia

**Zip:** 20014

**Location 6:**

**City:** Granada

**Contacts:**

***Contact 1:***

- **Email:** chidalgo72@gmail.com

- **Name:** Carmen Hidalgo Tenorio, MD

- **Role:** CONTACT

**Country:** Spain

**Facility:** Hospital Universitario Virgen de las Nieves

**Zip:** 18014

**Location 7:**

**City:** La Laguna

**Contacts:**

***Contact 1:***

- **Email:** remealeman@hotmail.com

- **Name:** Remedios Alemán, MD

- **Role:** CONTACT

**Country:** Spain

**Facility:** Hospital Universitario de Canarias

**Zip:** 38320

**Location 8:**

**City:** Logroño

**Contacts:**

***Contact 1:***

- **Email:** jalbaf@riojasalud.es

- **Name:** Jorge Alba Fernandez, MD

- **Role:** CONTACT

**Country:** Spain

**Facility:** Hospital San Pedro

**Zip:** 26006

**Location 9:**

**City:** Madrid

**Contacts:**

***Contact 1:***

- **Email:** victor.gonzalez@salud.madrid.org, vgramallo@gmail.com

- **Name:** Víctor José Gonzalez Ramallo, MD

- **Role:** CONTACT

**Country:** Spain

**Facility:** Hospital Universitario Gregorio Marañón

**Zip:** 28007

**Location 10:**

**City:** Madrid

**Contacts:**

***Contact 1:***

- **Email:** bloeches@yahoo.es

- **Name:** Belén Loeches, MD

- **Role:** CONTACT

**Country:** Spain

**Facility:** Hospital Universitario La Paz

**Zip:** 28046

**Location 11:**

**City:** Madrid

**Contacts:**

***Contact 1:***

- **Email:** jorge050390@gmail.com

- **Name:** Jorge Calderón Parra

- **Role:** CONTACT

**Country:** Spain

**Facility:** Hospital Universitario Puerta del Hierro

**Zip:** 28222

**Location 12:**

**City:** Málaga

**Contacts:**

***Contact 1:***

- **Email:** nonispc@hotmail.com

- **Name:** Antonio Plata Ciézar, MD

- **Role:** CONTACT

**Country:** Spain

**Facility:** Hospital Universitario Regional de Málaga

**Zip:** 29010

**Location 13:**

**City:** Málaga

**Contacts:**

***Contact 1:***

- **Email:** guilleojeda@me.com

- **Name:** Guillermo Ojeda Burgos, MD

- **Role:** CONTACT

**Country:** Spain

**Facility:** Hospital Universitario Virgen de la Victoria

**Zip:** 29010

**Location 14:**

**City:** Santander

**Contacts:**

***Contact 1:***

- **Email:** mcarmen.farinas@scsalud.es

- **Name:** Mª Carmen Fariñas, MD

- **Role:** CONTACT

***Contact 2:***

- **Name:** MD

- **Role:** CONTACT

**Country:** Spain

**Facility:** Hospital Universitario Marqués de Valdecilla

**Zip:** 39008

**Location 15:**

**City:** Sevilla

**Contacts:**

***Contact 1:***

- **Email:** luiselopezcortes@gmail.com

- **Name:** Luis Eduardo López Cortés, MD

- **Role:** CONTACT

**Country:** Spain

**Facility:** Hospital Universitario Virgen Macarena

**Zip:** 41009

**Location 16:**

**City:** Sevilla

**Contacts:**

***Contact 1:***

- **Email:** aa2406ge@yahoo.es

- **Name:** Cesar Aristides de Alarcon gonzalez, MD

- **Role:** CONTACT

**Country:** Spain

**Facility:** Hospital Universitario Virgen del Rocío

**Zip:** 41013

**Location 17:**

**City:** Terrassa

**Contacts:**

***Contact 1:***

- **Email:** bdgomezluengo@mutuaterrassa.es

- **Name:** Beatriz Dietl Gómez-Luengo, MD

- **Role:** CONTACT

**Country:** Spain

**Facility:** Hospital Universitari MútuaTerrassa

**Zip:** 08221

#### Overall Officials

**Official 1:**

**Affiliation:** Fundación para la Gestión de la Investigación en Salud de Sevilla

**Name:** HUVR Cesar Arístides de Alarcón González, MD-PhD

**Role:** PRINCIPAL_INVESTIGATOR

### IPD Sharing Statement Module

**Access Criteria:** Direct collaborators within the study

**Description:** The results will be shared with the investigators involved in the study, and will be shared when the analysis of the results is performed.

**Info Types:**

- STUDY_PROTOCOL

- SAP

- ICF

**IPD Sharing:** YES

**Time Frame:** 6 months

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000006331

- Term: Heart Diseases

- ID: D000002318

- Term: Cardiovascular Diseases

- ID: D000001424

- Term: Bacterial Infections

- ID: D000001423

- Term: Bacterial Infections and Mycoses

- ID: D000007239

- Term: Infections

- ID: D000053821

- Term: Cardiovascular Infections

### Condition Browse Module - Browse Branches

- Abbrev: BC01

- Name: Infections

- Abbrev: BC14

- Name: Heart and Blood Diseases

- Abbrev: All

- Name: All Conditions

- Abbrev: BC23

- Name: Symptoms and General Pathology

- Abbrev: Rare

- Name: Rare Diseases

### Condition Browse Module - Browse Leaves

- ID: M7859

- Name: Endocarditis, Bacterial

- Relevance: HIGH

- As Found: Infective Endocarditis

- ID: M7858

- Name: Endocarditis

- Relevance: HIGH

- As Found: Endocarditis

- ID: M9419

- Name: Heart Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M10283

- Name: Infections

- Relevance: LOW

- As Found: Unknown

- ID: M6368

- Name: Communicable Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M4722

- Name: Bacterial Infections

- Relevance: LOW

- As Found: Unknown

- ID: M12136

- Name: Mycoses

- Relevance: LOW

- As Found: Unknown

- ID: M4721

- Name: Bacterial Infections and Mycoses

- Relevance: LOW

- As Found: Unknown

- ID: M27489

- Name: Cardiovascular Infections

- Relevance: LOW

- As Found: Unknown

- ID: T3065

- Name: Infective Endocarditis

- Relevance: HIGH

- As Found: Infective Endocarditis

### Condition Browse Module - Meshes

- ID: D000004697

- Term: Endocarditis, Bacterial

- ID: D000004696

- Term: Endocarditis

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: All

- Name: All Drugs and Chemicals

### Intervention Browse Module - Browse Leaves

- ID: M4222

- Name: Anti-Bacterial Agents

- Relevance: LOW

- As Found: Unknown

- ID: M5693

- Name: Ceftriaxone

- Relevance: LOW

- As Found: Unknown

- ID: M4003

- Name: Ampicillin

- Relevance: LOW

- As Found: Unknown

- ID: M4224

- Name: Antibiotics, Antitubercular

- Relevance: LOW

- As Found: Unknown

### Misc Info Module

- Version Holder: 2024-05-31
