Partial Oral Treatment of Endocarditis

Study Overview
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Brief Summary
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Background Current management of infective endocarditis include admission and treatment with parenteral antibiotics for 4 weeks - 6 weeks. Resource demands and psychological issues of present management strategy make it highly relevant to seek for alternative more lenient alternatives. Experiences with oral treatment are only sporadically described, but observational data suggest that oral treatment could be a feasible option. The investigators have in 2010 treated 12 endocarditis patients with partial oral antibiotics with a 100% success rate. Study design The POET study is a Danish multicenter, prospective, randomized, open label study. The primary aim is to show non-inferiority of partial oral treatment with antibiotics of endocarditis compared to full parenteral treatment. Stable patients (n=400) with streptococci, staphylococci or enterococci infecting the mitral valve or the aortic valve will be included. After a minimum of 10 days of parenteral treatment, patients will be randomized to oral therapy or parenteral therapy. Special recommendations for oral treatment have been developed based on expected minimal inhibitory concentrations and pharmacokinetic calculations. Patients will be followed for 6 months after completion of antibiotic therapy. The primary endpoint is a composition of all cause mortality, unplanned cardiac surgery, embolic events and relapse of positive blood cultures with the primary pathogen.

Official Title
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Partial Oral Treatment of Endocarditis

Conditions
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Endocarditis

Intervention / Treatment
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* Drug: Oral treatment with antibiotics for endocarditis
* Drug: Guideline treatment with parenteral antibiotics


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Left-sided endocarditis based on the Duke criteria Infected with one of the following microorganisms: Streptococci Enterococcus faecalis Staphylococcus aureus Coagulase-negative staphylococci. ≥ 18 years At least 10 days of appropriate parenteral antibiotic treatment overall, and at least 1 week of appropriate parenteral treatment after valve surgery Afebrile (T < 38.0) > 2 days Decreasing infection parameters (CRP dropped to less than 25% of peak value or < 20 mg/l, and white blood cell count < 15 x 109/l) during antibiotic treatment No sign of abscess formation by echocardiography Transthoracic and transoesophageal echocardiography performed within 48 hours prior to randomization Exclusion Criteria: Body mass index > 40 Concomitant infection requiring intravenous antibiotic therapy Inability to give informed consent to participation Suspicion of reduced absorption of oral treatment due to abdominal disorder Reduced compliance

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 |
| --- | --- |
| Active Comparator: Guideline treatment with parenteral antibiotics<br>Guideline treatment with parenteral antibiotics | Drug: Guideline treatment with parenteral antibiotics<br> <br> |
| Experimental: Oral treatment with antibiotics<br>Oral treatment with antibiotics based on resistens pattern | Drug: Oral treatment with antibiotics for endocarditis<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint is a composite endpoint including all cause mortality, unplanned cardiac surgery, embolic events and relapse of positive blood cultures with the primary pathogen |  | Approximately 7 months. From randomisation until 6 months after end of study medication | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Quality of life | QOL performed during the study and after completion of the study | Approximately 7 months. From randomisation until 6 months after end of study medication | 
| Cost of treatment |  | Approximately 7 months. From randomisation until 6 months after end of study medication | 
| Duration of antibiotic therapy |  | Approximately 7 months. From randomisation until 6 months after end of study medication | 
| Complications related to intravenous catheter |  | 6 weeks |