Direct Thrombin Inhibitors Versus LMWH in Staphylococcus Aureus Bacteraemia

Study Overview
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Brief Summary
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Safety and efficacy of direct thrombin inhibitors versus enoxaparin in patients with staphylococcus aureus bacteraemia. The study hypothesizes that inhibition of the coagulase-activity of S. aureus by direct thrombin inhibitors is safe and translates into a better outcome of patients with S. aureus bacteremia.

Detailed Description
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Single center randomized controlled trial of direct thrombin inhibitors versus standard enoxaparin. Feasibility: proportion of patients eligible for randomization; clinically attained concentration of DTI and resulting staphylothrombin inhibition Safety: bleeding events (major/ clinically relevant non-major) Efficacy: thrombotic events during the thromboprophylactic treatment + 3 days Secondary outcome measures Coagulation parameters: evolution of D-dimers from day 0-4; other lab parameters of coagulation (PT/APTT/fibrinogen/platelet count) Inflammatory parameters: CRP, white blood cell count, neutrophilia Clinical outcomes: metastatic infections, assessed clinically or by PET/CT; relapse of S. aureus bacteremia; defervescence; persistent positive blood cultures; hospital stay, mortality.

Official Title
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Direct Thrombin Inhibitors Versus LMWH in Staphylococcus Aureus Bacteraemia. A Prospective Randomized Controlled Academic Single-centre Feasibility Study.

Conditions
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Staphylococcus Aureus Bacteraemia

Intervention / Treatment
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* Drug: direct thrombin inhibition
* Drug: enoxaparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive blood culture for staphylococcus aureus Symptoms or signs of infection Indication for thromboprophylaxis Exclusion Criteria: Contraindication for thromboprophylaxis Significant active bleeding or risk of excessive bleeding Heparin-induced thrombocytopenia Severe liver and kidney disease Pregnancy and lactation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: direct thrombin inhibition<br>dabigatran 110 mg BID, po argatroban (0.5 - 1 µg/kg/min) if peroral therapy is not possible | Drug: direct thrombin inhibition<br> <br> * Other names: argatroban;|
| Active Comparator: enoxaparin<br>enoxaparin 40 mg od, sc | Drug: enoxaparin<br> <br> * Other names: clexane;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Safety Outcome is the occurence of clinically-relevant bleeding events |  | From date of randomization up to end of study drug + 3 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary efficacy outcome is the occurence of metastatic infection | as documented with a PET-CTscan in eligible patients on D7-10 or clinically-overt metastatic infectious foci | From randomization until month 3 |