Existing guidelines recommend a duration of antibiotic treatment of endocarditis of 4-6 weeks one or more types of intravenously administered antibiotics. The long hospitalization increases several risks for the patient, including mental strain and increased loss of function. Furthermore, it poses a significant financial burden on the health systems. Current guidelines fail to use available clinical and paraclinical, data collected from patients (echo, temperature, CRP, leukocytes, procalcitonin etc.) to determine duration of treatment. A strategy including these data in treatment algorithms ensures an individualized treatment, targeting the individual patient's course and response to treatment. Thus, the purpose of this open-label, prospective, non-inferiority, RCT study is to investigate the safety and effectiveness of shortening treatment of endocarditis based on the individual patient's initial treatment response, sampling 475 patients, approx. 125 patients with each type of bacteria (Streptococci; Enterococcus faecalis; Staphylococcus aureus). Interim analysis will be conducted when 150 patients have been included, to assess the frequency of the event rate and inclusion rate in order to adjust the intended size of the study population. Due to an administrative error, this study has been registered twice on clinicaltrials.gov under identifiers NCT05144399 (original) and NCT03851575 (duplicate). As per July 2026, both records have been updated to unanimously reflect study status and final protocol. Historical versions of the clinicaltrials.gov registration and updates are available under the respective registration ID's (2018-2020 updates under clinicaltrials.gov registration with ID NCT05144399, 2021-2026 updates clinicaltrials.gov registration with ID NCT03851575).
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
508
E. faecalis uncomplicated: 4 weeks. E. faecalis complicated: 4 weeks. S. aureus uncomplicated: 2 weeks. S. aureus complicated: 4 weeks. Streptococci spp. NVE: 2 weeks. Streptococci spp. PVE or abscess: 3 weeks. Subsequent to cardiac surgery with a negative valve culture (organism NOT grown in laboratory from valve): Minimum 1 week after surgery regardless of previous antibiotic treatment received. Subsequent to cardiac surgery with a positive valve culture (organism grown in laboratory from valve): treatment will continue with the start date of antibiotics changed to the date of surgery. Complicated IE defined as patients with abscess, embolic event, surgically treated IE, and/or PVE. NVE: native valve endocarditis, PVE: prosthetic valve endocarditis.
E. faecalis uncomplicated: 6 weeks. E. faecalis complicated: 6 weeks. S. aureus uncomplicated: 4 weeks. S. aureus complicated: 6 weeks. Streptococci spp. NVE: 4 weeks. Streptococci spp. PVE or abscess: 6 weeks. Subsequent to cardiac surgery with a negative valve culture (organism NOT grown in laboratory from valve): Minimum 2 weeks after surgery regardless of previous antibiotic treatment received. Subsequent to cardiac surgery with a positive valve culture (organism grown in laboratory from valve): treatment will continue with the start date of antibiotics changed to the date of surgery. Complicated IE defined as patients with abscess, embolic event, surgically treated IE, and/or PVE. NVE: native valve endocarditis, PVE: prosthetic valve endocarditis.
Brigham and Womens Hospital
Boston, Massachusetts, United States
Skejby Sygehus
Aarhus, Denmark
Rigshospitalet
Copenhagen, Denmark
Bispebjerg Hospital
Copenhagen, Denmark
Gødstrup Regional Hospital
Gødstrup, Denmark
Herlev Hospital
Herlev, Denmark
Hillerød Hospital
Hillerød, Denmark
Hvidovre Hospital
Hvidovre, Denmark
Odense sygehus
Odense, Denmark
Roskilde Sygehus, Zealand University hospital
Roskilde, Denmark
...and 3 more locations
Combined safety endpoint of: All cause mortality, embolic episodes, not planned Heart surgery
The primary endpoint is a combined endpoint consisting of the following events occurring within six months after the earliest time of potential treatment discontinuation: Death; Embolisms; Heart surgery not planned at the time of randomization.
Time frame: 6 months after randomization
Primary efficacy endpoint: Difference in number of days alive without antibiotic treatment for endocarditits and/or bacteremia between the two study groups
The primary efficacy endpoint is the difference in number of days alive without antibiotic treatment for endocarditits and/or bacteremia between the two study groups, assessed from and until 6 months after randomization.
Time frame: 6 months after randomization
Expenses associated with admission and treatment
Combined endpoint consisting of expenses due to i admission ii medication iii transportation iv surgery v imaging vi home care
Time frame: 6 months after randomization
Duration of admission
Duration of admission
Time frame: 6 months after randomization
Duration of antibiotic treatment
Duration of antibiotic treatment
Time frame: 6 months after randomization
Frequency of catheter complication
Frequency of catheter complication
Time frame: 6 months after randomization
Unplanned Heart surgery
• Unplanned cardiac valve surgery defined as any cardiac surgery which is not planned at the time of randomization. Data will be extracted from the electronic patient journal.
Time frame: 6 months after randomization
All cause mortality
All cause mortality
Time frame: 6 months after randomization
Embolic events
Embolic events
Time frame: 6 months after randomization
Re-bacteremia with the primary pathogen
• Relapse of bacteremia defined as a positive blood culture with the same microorganism as during the initial IE admission (streptococci spp., S. aureus, or E. faecalis). Data will be extracted from the electronic patient journal.
Time frame: 6 months after randomization
Quality of life assesment
Quality of life assessed by completing short version 36 (SF 36) version 2
Time frame: 6 monts after randomization and after
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