Enterococcal EndocarditisPhase 4FOURSIXNCT05398289
FOUR-SIX TRIAL for the Treatment of Enterococcal Endocarditis
A Phase 4 study testing 4-week duration of antibiotic therapy and 6-week duration of antibiotic therapy in people with Enterococcal Endocarditis, run by University Magna Graecia.
Trial summary
Duration of therapy in severe infections has a high impact in term of compliance, adverse events, and costs but also in term of antibiotic pressure on selection of multidrug-resistant pathogens. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Enterococcal Endocarditis
- What is being tested?
- 4-week duration of antibiotic therapy and 6-week duration of antibiotic therapy
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 130 participants
- Where
- No sites listed yet
- Study dates
- 1 Jan 2024to 1 Sep 2026
- Phase
- Phase 4
- Are there results?
- None posted in the registry
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
- documented infective endocarditis due to enterococcal strains, according to the modified Duke criteria.
Who cannot join
- patients candidate for chronic suppressive antibiotic treatment
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Four-week Duration Versus 6-week Duration of Therapy for the Treatment of Enterococcal Endocarditis
Duration of therapy in severe infections has a high impact in term of compliance, adverse events, and costs but also in term of antibiotic pressure on selection of multidrug-resistant pathogens. In this context, many advancements have been obtained for an early diagnosis of IE with a strict selection of criteria for surgery. Moreover, the use in antibiotic regimen of new drugs with peculiar PK/PD characteristics, as a quick bactericidal action, also for IE was not accompanied to a revaluation of duration of antibiotic treatment. On this basis, US and European guidelines recommend a 6-week duration of antibiotic treatment for IE due to enterococcal species.
AIM 1: To evaluate a 4-week duration of antibiotic therapy versus a 6-week duration according to international guidelines.
Read more
AIM 2: Second aim is to evaluate the PK/PD of antimicrobials in relation to the probability of target attainment (PTA) of optimal exposure against enterococci.
AIM 3: Finally, we will analyze the bactericidal activities of antibiotic combinations used in patients with IE and the survival of the subgroup of patients who underwent surgery.
Open-label, multicenter, randomized, non-inferiority trial to be conducted in a 3-year period. The institutional review board at each site will approve the protocol, and all patients or their authorized representatives will provide written informed consent. Eligible patients will be 18 years of age or older with a documented IE due to enterococcal strains, according to the modified Duke criteria.
63 patients in each of the two arms. The study will be conducted at Italian sites. Data on demographic characteristics, comorbidities, antibiotic and concomitant therapies will be collected. Baseline treatments will be defined according to the patients' pharmacological history. IE will be defined according to modified Duke criteria. Antibiotic treatment, indications and timing of surgery will be based on the 2015 American Heart Association and European Society of Cardiology guidelines.
Blood samples for determining antibiotic concentrations of ampicillin, gentamicin, vancomycin, daptomycin and linezolid will be collected at predetermined times in order to allow estimation of PK/PD.
Randomization:
- 4-week duration of antibiotic therapy
- standard 6-week duration of antibiotic therapy The intention-to-treat population (ITT) will include all randomized patients. The modified intention-to-treat population (mITT) will include all randomized patients receiving at least one dose of study medication. The clinically evaluable (CE) population will include ITT patients demonstrating sufficient adherence to study protocol.
Primary endpoint: non-inferiority of a 4-week course in terms of outcome at 60 days.
Secondary endpoints: microbiological eradication, pharmacological concentrations of antibiotic regimens, patients undergoing surgery, duration of therapy according with resistance profile of enterococcal species.
- Conditions
- Enterococcal Endocarditis
- Being tested
- 4-week duration of antibiotic therapy, 6-week duration of antibiotic therapy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
4-week duration of antibiotic therapyDrug
The aim is to show non-inferiority of a 4-week duration of antibiotic therapy versus a standard 6-week duration according to international guidelines
6-week duration of antibiotic therapyDrug
The aim is to show non-inferiority of a 4-week duration of antibiotic therapy versus a standard 6-week duration according to international guidelines
| Study group | Role | What they receive |
|---|---|---|
| 4-week duration of antibiotic therapy | Experimental | Not described Receives: Drug: 4-week duration of antibiotic therapy |
| standard 6-week duration of antibiotic therapy | Active comparator | Not described Receives: Drug: 6-week duration of antibiotic therapy |
What is being measured
The primary outcome is the main question the study is designed to answer.
A 4-week course of effective antimicrobial therapy
To evaluate clinical cure after 4 weeks of therapy
Measured: at 30 days and after 60 days from enrollment
Secondary outcomes (2)
Microbiological clearance of Enterococcus spp from blood cultures
Time to microbiological clearance from blood
Measured: From inclusion, up to 30 days
Surgical Procedure
Time to surgery
Measured: From inclusion, up to 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted31 May 2022
- Study start1 Jan 2024 (estimated)
- Primary completion1 Sep 2024 (estimated)
- Study completion1 Sep 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Enterococcal EndocarditisStudies 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
- Masking
- None (open label)
- Enrolment
- 130 participants (estimated)
Sponsor and investigators
- Lead sponsor
- University Magna Graecia
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Alessandro Russo, University Magna Graecia
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05398289
- Sponsor's protocol ID
- FST_2022
- Acronym
- FOURSIX
- Status last verified
- May 2023
- First submitted
- 19 May 2022
- Last updated
- 10 May 2023
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Four-week Duration Versus 6-week Duration of Therapy for the Treatment of Enterococcal Endocarditis
- ClinicalTrials.gov ID
- NCT05398289
- Acronym / sponsor ID
- FOURSIX / FST_2022
- Conditions
- Enterococcal Endocarditis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 130 participants (estimated)
- Lead sponsor
- University Magna GraeciaUniversity, hospital or other
- Study start
- 1 Jan 2024 (estimated)
- Primary completion
- 1 Sep 2024 (estimated)
- Study completion
- 1 Sep 2026 (estimated)
- First posted
- 31 May 2022 (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.
Duration of therapy in severe infections has a high impact in term of compliance, adverse events, and costs but also in term of antibiotic pressure on selection of multidrug-resistant pathogens. In this context, many advancements have been obtained for an early diagnosis of IE with a strict selection of criteria for surgery. Moreover, the use in antibiotic regimen of new drugs with peculiar PK/PD characteristics, as a quick bactericidal action, also for IE was not accompanied to a revaluation of duration of antibiotic treatment. On this basis, US and European guidelines recommend a 6-week duration of antibiotic treatment for IE due to enterococcal species.
AIM 1: To evaluate a 4-week duration of antibiotic therapy versus a 6-week duration according to international guidelines.
AIM 2: Second aim is to evaluate the PK/PD of antimicrobials in relation to the probability of target attainment (PTA) of optimal exposure against enterococci.
AIM 3: Finally, we will analyze the bactericidal activities of antibiotic combinations used in patients with IE and the survival of the subgroup of patients who underwent surgery.
Open-label, multicenter, randomized, non-inferiority trial to be conducted in a 3-year period. The institutional review board at each site will approve the protocol, and all patients or their authorized representatives will provide written informed consent. Eligible patients will be 18 years of age or older with a documented IE due to enterococcal strains, according to the modified Duke criteria.
63 patients in each of the two arms. The study will be conducted at Italian sites. Data on demographic characteristics, comorbidities, antibiotic and concomitant therapies will be collected. Baseline treatments will be defined according to the patients' pharmacological history. IE will be defined according to modified Duke criteria. Antibiotic treatment, indications and timing of surgery will be based on the 2015 American Heart Association and European Society of Cardiology guidelines.
Blood samples for determining antibiotic concentrations of ampicillin, gentamicin, vancomycin, daptomycin and linezolid will be collected at predetermined times in order to allow estimation of PK/PD.
Randomization:
- 4-week duration of antibiotic therapy
- standard 6-week duration of antibiotic therapy The intention-to-treat population (ITT) will include all randomized patients. The modified intention-to-treat population (mITT) will include all randomized patients receiving at least one dose of study medication. The clinically evaluable (CE) population will include ITT patients demonstrating sufficient adherence to study protocol.
Primary endpoint: non-inferiority of a 4-week course in terms of outcome at 60 days.
Secondary endpoints: microbiological eradication, pharmacological concentrations of antibiotic regimens, patients undergoing surgery, duration of therapy according with resistance profile of enterococcal species.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 4-week duration of antibiotic therapy | Experimental | Drug: 4-week duration of antibiotic therapy |
| standard 6-week duration of antibiotic therapy | Active comparator | Drug: 6-week duration of antibiotic therapy |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- documented infective endocarditis due to enterococcal strains, according to the modified Duke criteria.
Key exclusion criteria (1 listed)
- patients candidate for chronic suppressive antibiotic treatment
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 |
|---|---|---|
| 4-week duration of antibiotic therapyThe aim is to show non-inferiority of a 4-week duration of antibiotic therapy versus a standard 6-week duration according to international guidelines | Drug | 4-week duration of antibiotic therapy |
| 6-week duration of antibiotic therapyThe aim is to show non-inferiority of a 4-week duration of antibiotic therapy versus a standard 6-week duration according to international guidelines | Drug | standard 6-week duration of antibiotic therapy |
Primary outcome
A 4-week course of effective antimicrobial therapy
Time frame: at 30 days and after 60 days from enrollment
To evaluate clinical cure after 4 weeks of therapy
2 secondary outcomes
Microbiological clearance of Enterococcus spp from blood cultures
Time frame: From inclusion, up to 30 days
Surgical Procedure
Time frame: From inclusion, up to 30 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 May 2023.
- Individual participant dataSharing planned: No
Related trials for Enterococcal Endocarditis
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From Commensalism to Pathogenicity: Exploring the Pathophysiology of Bacteremia to Better Understand Enterococcus Faecalis Infective Endocarditis
Infective Endocarditis (IE)
RecruitingPhase 4
Ampicillin and Ceftriaxone for the Treatment of Enterococcus Faecalis Infective Endocarditis.
Endocarditis, Infective
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. This study is not recruiting at the moment.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing 4-week duration of antibiotic therapy and 6-week duration of antibiotic therapy in people with Enterococcal Endocarditis, run by University Magna Graecia.
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 1 inclusion and 1 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: status not confirmed, as of the sponsor's last update on 10 May 2023. Status can change between updates, so confirm with the study contact before making plans.
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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Alessandro Russo, Prof. (+39 09613647552, a.russo@unicz.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
A 4-week course of effective antimicrobial therapy (time frame: at 30 days and after 60 days from enrollment). 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 10 May 2023.