FOUR-SIX TRIAL for the Treatment of Enterococcal Endocarditis

NCT05398289 | Not Yet Recruiting Phase 4 DMC

• 1 other identifier: FST_2022
• Study Type: interventional
• Target: 130
• Locations: 0 countries
• Sites: N/A

Brief 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. 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:

1. 1.4-week duration of antibiotic therapy
2. 2.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.

Conditions

Enterococcal Endocarditis

Outcome Measures

Primary Outcomes (1)

• A 4-week course of effective antimicrobial therapy

  To evaluate clinical cure after 4 weeks of therapy

  at 30 days and after 60 days from enrollment

Secondary Outcomes (2)

• Microbiological clearance of Enterococcus spp from blood cultures

  From inclusion, up to 30 days

• Surgical Procedure

  From inclusion, up to 30 days

Study Arms (2)

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

Interventions

4-week duration of antibiotic therapy DRUG

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

4-week duration of antibiotic therapy

6-week duration of antibiotic therapy DRUG

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

standard 6-week duration of antibiotic therapy

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• documented infective endocarditis due to enterococcal strains, according to the modified Duke criteria.

You may not qualify if:

• patients candidate for chronic suppressive antibiotic treatment

Sponsors & Collaborators

• University Magna Graecia: lead

Central Study Contacts

Alessandro Russo, Prof.

CONTACT

+39 09613647552; a.russo@unicz.it

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: May 19, 2022
• First Posted: May 31, 2022
• Study Start: January 1, 2024
• Primary Completion: September 1, 2024
• Study Completion (Estimated): September 1, 2026
• Last Updated: May 10, 2023

Record last verified: 2023-05

Data Sharing

• IPD Sharing: Will not share