Accelerated Treatment of Endocarditis

Study Overview
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Brief Summary
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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 750 patients, approx. 200 patients with each type of bacteria (Streptococci; Enterococcus faecalis; Staphylococcus aureus).

Official Title
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Accelerated Treatment of Endocarditis

Conditions
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Endocarditis

Intervention / Treatment
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* Other: Accelerated antibiotic treatment
* Other: Standard treatment length


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Admitted with infectious endocarditis (duke criteria) < 14 days of relevant antibiotic treatment for endocarditis One of the following bacteria: Streptococci, enterococcus faecalis, staphylococcus aureus Exclusion Criteria: Known immune incompetency, Relapse endocarditis with 6 months, Unable to give informed concent

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Accelerated antibiotic treatment<br>Patients are treated shorter than usual | Other: Accelerated antibiotic treatment<br>* 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.<br>|
| Other: Standard length of antibiotic treatment<br>Patients are receiving the standard length of antibiotic treatment | Other: Standard treatment length<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Combined endpoint of: All cause mortality, Bacteremia with primary pathogen, 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; Bacteraemia with the same microorganism; Heart surgery not planned at the time of randomization. | 6 months after randomization | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 6 months after randomization | 
| Duration of admission | Duration of admission | 6 months after randomization | 
| Duration of antibiotic treatment | Duration of antibiotic treatment | 6 months after randomization | 
| Frequency of catheter complication | Frequency of catheter complication | 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. | 6 months after randomization | 
| All cause mortality | All cause mortality | 6 months after randomization | 
| Embolic events | Embolic events | 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. | 6 months after randomization |