Overview
Sponsor-declared trial summary
Phase
Therapeutic use (Phase IV)
Status
Ongoing, recruiting
Participants planned
284
Countries
1
Sites
18
Enterococcus faecalis infectious endocarditis
To demonstrate that continuous infusion ampicillin-ceftriaxone administration is non-inferior in efficacy to standard treatment in patients with Enterococcus faecalis infective endocarditis defined as frequency of disease recurrence.
Key facts
- Sponsor
- Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla
- Participant type
- Patients
- Age range
- 18-64 years, 65+ years
- Gender
- Male and Female
- Therapeutic area
- Diseases [C] - Skin and Connective Tissue Diseases [C17], Diseases [C] - Bacterial Infections and Mycoses [C01]
- Trial duration
- 9 Oct 2024 → ongoing
- Decision date (initial)
- 2024-07-30
- Transition trial
- No
- Low-intervention
- Yes
- Rare-disease indication
- No
- Vulnerable population
- No
Trial design
CTIS Part I — objectives, methods, condition coding
Main objective
Scope: Efficacy
To demonstrate that continuous infusion ampicillin-ceftriaxone administration is non-inferior in efficacy to standard treatment in patients with Enterococcus faecalis infective endocarditis defined as frequency of disease recurrence.
Secondary objectives 9
- To demonstrate that continuous infusion ampicilline-ceftriaxone administration is non-inferior in efficacy to standard treatment in patients with Enterococcus faecalis infective endocarditis defined as mortality frequency
- To determine whether the continuous infusion regimen is non-inferior to to standard treatment in terms of unplanned surgery.
- To evaluate the rate of unplanned readmissions for any reason in patients treated with the continuous infusion regimen compared with the istandard treatment.
- To analyze and compare adverse events related to study antibiotics in both treatment arms.
- To analyze and compare the efficiency of both treatment arms in number of days of hospital stay avoided and healthcare-related infections.
- To study the strains responsible for the recurrences and their similarity to the strain responsible for the original episode, to check whether they are recurrences (same strain) or reinfections (different strains).
- To confirm the ability of ampicilline-ceftriaxone in continuous and intermittent infusion to maintain synergistic serum concentrations of both drugs for 24 hours
- To describe the pharmacokinetic profile of ampicillin and ceftriaxone in continuous and intermittent infusion.
- To analyze the synergistic activity between ampicillin and ceftriaxone in the isolates responsible for the relapses, comparing them with a control group.
Conditions and MedDRA coding
Enterococcus faecalis infectious endocarditis
| Version | Level | Code | Term | System organ class |
|---|---|---|---|---|
| 20.0 | PT | 10014671 | Endocarditis enterococcal | 100000004862 |
Eligibility criteria
Principal inclusion / exclusion criteria as submitted by sponsor
Inclusion criteria 3
- Adult patients (18 years of age or older)
- Possible or definitive diagnosis of infective endocarditis due to Enterococcus faecalis according to the Duke-ISCVID criteria
- Signed informed consent of patients
Exclusion criteria 3
- Allergy to penicillins or cephalosporins
- Pregnancy and lactation
- Polymicrobial infection including microorganisms different to E. faecalis
Endpoints
Primary and secondary outcome measures (English text)
Primary endpoints 1
- Treatment failure defined as confirmed recurrence of infective endocarditis due to Enterococcus faecalis (microbiological failure) one year after completion of antibiotic treatment
Secondary endpoints 9
- Treatment failure assessed up to one year after completion of treatment and defined as follows: mortality (therapeutic failure) from any cause during hospitalization or from endocarditis-related causes throughout the study.
- Number of unplanned cardiac surgeries during the entire study.
- Number of unplanned readmissions during the entire trial.
- Number of medication-related adverse events from randomisation until 30 days after the last dose administered.
- Total number of antibiotic treatment days, number of TADE treatment days in those patients who receive continuous infusion (experimental arm) and their site has a TADE programme, and number of healthcare-associated infections throughout the trial.
- Confirmed recurrence of Enterococcus faecalis infective endocarditis throughout the study.
- Minimum free serum concentration and steady-state plasma concentration of ceftriaxone and ampicillin for 24 hours on day 14 after initiation of treatment (visit 2) in the experimental arm.
- Pharmacokinetic parameters (volume of distribution, clearance, elimination constant) of ceftriaxone and ampicillin on day 14 after initiation of treatment (visit 2).
- Synergistic activity will be calculated through the reduction of the Minimum Inhibitory Concentration of ampicillin induced by ceftriaxone in the strains responsible for recurrences and control strains.
Investigational products
Investigational medicinal products (IMPs), comparators, placebo, auxiliary
Test 2
SCP126209 · ATC
- Active substance
- Ampicillin Sodium
- Route of administration
- INTRAVENOUS
- Max daily dose
- 12 g gram(s)
- Max total dose
- 504 g gram(s)
- Max treatment duration
- 42 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01CA01 — AMPICILLIN
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
SCP1153452 · ATC
- Active substance
- Ceftriaxone Sodium
- Route of administration
- INTRAVENOUS
- Max daily dose
- 4 g gram(s)
- Max total dose
- 168 g gram(s)
- Max treatment duration
- 42 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01DD04 — CEFTRIAXONE
- Marketing authorisation
- -
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Auxiliary 8
Linezolid Demo 2 mg/ml solución para perfusión EFG
PRD3321197 · Product
- Active substance
- Linezolid
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 1200 mg milligram(s)
- Max total dose
- 33600 mg milligram(s)
- Max treatment duration
- 28 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01XX08 — LINEZOLID
- Marketing authorisation
- 80350
- MA holder
- DEMO ABEE
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Linezolid Teva Pharma 600 mg comprimidos recubiertos con película EFG
PRD2403658 · Product
- Active substance
- Linezolid
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 1200 mg milligram(s)
- Max total dose
- 33600 mg milligram(s)
- Max treatment duration
- 28 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01XX08 — LINEZOLID
- Marketing authorisation
- 79489
- MA holder
- TEVA PHARMA S.L.U.,
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
PRD421291 · Product
- Active substance
- Rifampicin
- Substance synonyms
- RIFAMPIN
- Pharmaceutical form
- CAPSULE, HARD
- Route of administration
- ORAL
- Max daily dose
- 1200 mg milligram(s)
- Max total dose
- 33600 mg milligram(s)
- Max treatment duration
- 28 Day(s)
- Authorisation status
- Authorised
- ATC code
- J04AB02 — RIFAMPICIN
- Marketing authorisation
- 46029
- MA holder
- SANOFI-AVENTIS, S.A.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Teicoplanina Sala 200 mg polvo para solución inyectable y para perfusión EFG.
PRD11904820 · Product
- Active substance
- Teicoplanin
- Substance synonyms
- Teichomycin A2
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 12 mg/kg milligram(s)/kilogram
- Max total dose
- 336 mg/kg milligram(s)/kilogram
- Max treatment duration
- 28 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01XA02 — TEICOPLANIN
- Marketing authorisation
- 78.750
- MA holder
- LABORATORIO REIG JOFRE, S.A.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Amoxicilina Teva 1.000 mg comprimidos EFG
PRD11888891 · Product
- Active substance
- Amoxicillin
- Substance synonyms
- AMOXICILLINE, AMOXICILLINUM
- Pharmaceutical form
- TABLET
- Route of administration
- ORAL
- Max daily dose
- 4 g gram(s)
- Max total dose
- 112 g gram(s)
- Max treatment duration
- 28 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01CA04 — AMOXICILLIN
- Marketing authorisation
- 66643
- MA holder
- TEVA PHARMA S.L.U.,
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Moxifloxacino Sandoz 400 mg comprimidos recubiertos con película EFG
PRD2849191 · Product
- Active substance
- Moxifloxacin
- Pharmaceutical form
- FILM-COATED TABLET
- Route of administration
- ORAL
- Max daily dose
- 400 mg milligram(s)
- Max total dose
- 11200 mg milligram(s)
- Max treatment duration
- 28 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01MA14 — MOXIFLOXACIN
- Marketing authorisation
- 74573
- MA holder
- SANDOZ FARMACÉUTICA, S.A.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Dalbavancina Sala 500 mg polvo para concentrado para solución para perfusión EFG
PRD11329629 · Product
- Active substance
- Dalbavancin
- Pharmaceutical form
- SOLUTION FOR INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 3000 mg milligram(s)
- Max total dose
- 64500 mg milligram(s)
- Max treatment duration
- 28 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01XA04 — -
- Marketing authorisation
- 89545
- MA holder
- LABORATORIO REIG JOFRE, S.A.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Daptomicina Accord 500 mg polvo para solución inyectable y para perfusión EFG
PRD5581438 · Product
- Active substance
- Daptomycin
- Pharmaceutical form
- SOLUTION FOR INJECTION/INFUSION
- Route of administration
- INTRAVENOUS
- Max daily dose
- 12 mg/kg milligram(s)/kilogram
- Max total dose
- 336 mg/kg milligram(s)/kilogram
- Max treatment duration
- 28 Day(s)
- Authorisation status
- Authorised
- ATC code
- J01XX09 — -
- Marketing authorisation
- 82320
- MA holder
- ACCORD HEALTHCARE S.L.U.
- MA country
- Spain
- Paediatric formulation
- No
- Orphan designation
- No
- Modified vs. Marketing Authorisation
- No
Sponsors and contacts
Sponsor organisations, regulatory contacts, third parties
Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla
- Sponsor organisation
- Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla
- Address
- Avenida De Manuel Siurot Sn
- City
- Sevilla
- Postcode
- 41013
- Country
- Spain
Scientific contact point
- Organisation
- Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla
- Contact name
- Clinical Trial Unit IBIS/University Hospital Virgen del Rocío
Public contact point
- Organisation
- Fundacion Publica Andaluza Para La Gestion De La Investigacion En Salud De Sevilla
- Contact name
- Clinical Trial Unit IBIS/University Hospital Virgen del Rocío
Locations
1 EU/EEA country · 18 investigational sites
By country
| Country | MS status | Planned subjects | Sites |
|---|---|---|---|
| Spain | Ongoing, recruiting | 284 | 18 |
| Rest of world | — | 0 | — |
Investigational sites
Hospital Universitario Araba
infectious diseases, Jose Achotegui Kalea S/N, 01009, Vitoria
Hospital Universitario De Cruces
infectious diseases, Cruces Plaza S/n, 48903, Barakaldo
Hospital Universitario Puerta De Hierro De Majadahonda
Internal Medicine, Calle De Joaquin Dicenta 2, 28029, Madrid
Hospital Universitario Clínico San Carlos
infectious diseases, Calle Del Profesor Martin Lagos S/N, 28040, Madrid
Hospital Universitario Regional De Malaga
infectious diseases, Avenida De Carlos De Haya Sn, 29010, Malaga
Hospital Universitario Virgen De La Victoria
infectious diseases, Calle Del Arroyo Teatinos Sn, 29010, Malaga
University Hospital Virgen Del Rocio S.L.
infectious diseases, Avenida De Manuel Siurot S/n, 41013, Sevilla
Hospital San Pedro
infectious diseases, Calle Piqueras 98, 26006, Logrono
Hospital Universitario De Canarias
infectious diseases, Calle Ofra Sn La Cuesta, 38320, La Laguna
Hospital Clinic De Barcelona
infectious diseases, Calle Villarroel 170, 08036, Barcelona
Hospital Universitario Virgen De La Macarena
infectious diseases, Avenida Del Doctor Fedriani 3, 41009, Sevilla
Hospital Universitario Donostia
infectious diseases, Pasealeku Doct. Begiristain 109, 20014, Donostia
Hospital General Universitario Gregorio Maranon
infectious diseases, Calle Del Doctor Esquerdo 46, 28009, Madrid
Hospital Universitario Marques De Valdecilla
infectious diseases, Avenida Valdecilla Sn, 39008, Santander
Hospital Universitario Virgen De Las Nieves
infectious diseases, Avenida De Las Fuerzas Armadas 2, 18014, Granada
Hospital Universitario La Paz
infectious diseases, Paseo De La Castellana 261, 28046, Madrid
Hospital Universitari Vall D Hebron
infectious diseases, Passeig De La Vall D'Hebron 119-129, 08035, Barcelona
Hospital Universitari Mutua Terrassa
infectious diseases, Plaza del Dr. Robert 5, 08221, Terrassa
Country notifications
Trial-start, recruitment-start, end and early-termination notifications submitted per Member State
| Country | Trial start | Trial end | Recruitment start | Recruitment end | Early termination |
|---|---|---|---|---|---|
| Spain | 2024-10-09 | 2024-10-15 |
Results and documents
Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial
Documents 11 files
Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.
| Type | Title | Version |
|---|---|---|
| Protocol (for publication) | Protocol_2024-511719-40-00 | 2.0 |
| Protocol (for publication) | Protocol_2024-511719-40-00 V 1_1 con cambios | 2.0 |
| Recruitment arrangements (for publication) | K1_ Recruitment arrangements_DOBLEI | 1 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults CRF adults_DOBLEI V1 | 2.0 |
| Subject information and informed consent form (for publication) | L1_SIS and ICF adults_DOBLEI V 2_0 con cambios | 2.0 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC Ampicillin | 1 |
| Summary of Product Characteristics (SmPC) (for publication) | E2_SmPC ceftriaxone Jul2024 | 1 |
| Synopsis of the protocol (for publication) | Protocol synopsis 2024-511719-40-00_English | 2.0 |
| Synopsis of the protocol (for publication) | Protocol synopsis 2024-511719-40-00_English w changes | 2.0 |
| Synopsis of the protocol (for publication) | Protocol synopsis 2024-511719-40-00_Spanish | 2.0 |
| Synopsis of the protocol (for publication) | Protocol synopsis 2024-511719-40-00_Spanish con cambios | 2.0 |
Application history
5 submissions — initial application plus substantial / non-substantial modifications
| # | Type | Code | Submitted | Reference MS | Conclusion | Decision date |
|---|---|---|---|---|---|---|
| 1 | INITIAL | IN | 2024-05-07 | Spain | Acceptable 2024-07-30
|
2024-07-30 |
| 2 | SUBSTANTIAL MODIFICATION | SM-2 | 2024-08-26 | Spain | Acceptable | 2024-10-02 |
| 3 | SUBSTANTIAL MODIFICATION | SM-4 | 2025-05-08 | Spain | Acceptable 2025-06-16
|
2025-06-16 |
| 4 | SUBSTANTIAL MODIFICATION | SM-5 | 2025-06-25 | Spain | Acceptable | 2025-07-16 |
| 5 | SUBSTANTIAL MODIFICATION | SM-6 | 2026-02-03 | Spain | Acceptable | 2026-02-17 |