Infectious Endocarditis
Conditions
Brief summary
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)
Interventions
OTHERAccelerated treatment of endocarditis
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.
OTHERUsual guideline therapy
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.
Sponsors
Rigshospitalet, Denmark
Herlev Hospital
Nordsjaellands Hospital
Zealand University Hospital
Odense University Hospital
Aarhus University Hospital
Lund University Hospital
Bispebjerg Hospital
Hvidovre University Hospital
Vejle Hospital
Viborg Regional Hospital
Gødstrup Hospital
Brigham and Women's Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Patients hospitalized and diagnosed with bacterial, left-sided endocarditis as determined by the department clinician responsible based on the revised Duke criteria. 2. The patient may be included \<14 days after beginning of relevant antibiotic treatment. 3. Left-sided endocarditis with one of the following microorganisms: Streptococci; Enterococcus faecalis; Staphylococcus aureus. 4. Patients ≥ 18 years.
Exclusion criteria
1. Known / suspected immunocompetence (HIV, chemotherapy, prednisolone treatment (\> 20 mg / day)). 2. Incapability to give informed consent for participation. 3. Relapse Endocarditis (Endocarditis with the same bacteria within six months).
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Combined safety endpoint of: All cause mortality, embolic episodes, not planned Heart surgery | 6 monts after randomization | 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. |
| Primary efficacy endpoint: Difference in number of days alive without antibiotic treatment for endocarditits and/or bacteremia between the two study groups | 6 months after randomization | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Expenses | 6 monts after randomization | Expenses associated with hospitalization and treatment of the disease. I.E., expenses to admission, examinations and medicine |
| Duration of antibiotic treatment | 6 months after randomization | Duration of antibiotic treatment |
| Duration of hospitalization | 6 monts after randomization | Duration of hospitalization |
| Frequency of catheter complication | 6 months after randomization | Frequency of catheter complication |
| Surgery not planned at randomization | 6 monts after randomization | Number of patients that have Surgery not planned at randomization |
| Death | 6 monts after randomization | Number of patients that die |
| Embolisms | 6 monts after randomization | Number of patients that have an embolism |
| Bacteraemia with the same microorganism, | 6 monts after randomization | Number of patients that have Bacteraemia with the same microorganism |
| Quality of life assesment | 6 monts after randomization and after | Quality of life assessed by completing short version 36 (SF 36) version 2 |
Countries
Denmark, Sweden, United States
Contacts
STUDY_CHAIRHenning Bundgaard, MD
Rigshospitalet, Denmark
Outcome results
None listed