Pharmacokinetics and Point of Care Testing of Direct Oral Anticoagulants Subjects

Study Overview
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Brief Summary
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DOACs are increasingly used since 8 years. Standard coagulation tests (Prothrombin time [PT] and activated partial thromboplastin time [aPTT]) from plasma samples show a high variation. Special coagulation tests like hemoclot for dabigatran and chromogenic substrate assays for Rivaroxaban, Apixaban, and Edoxaban are time-consuming and can be performed only in specialized laboratories. In specific medical situations like in patients such as emergency procedures, stroke (before starting thrombolytic therapy), trauma, general surgery or other invasive procedures, it may be necessary for medical decision making to know the presence or absence of a DOAC in patient's body fluid. Until now there is no rapid, specific and sensitive coagulation test available in the market.

Detailed Description
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This prospective, open-label, controlled, not randomized trial in healthy volunteers to investigate comparatively the pharmacokinetics of the direct oral anticoagulants in plasma and in urine with LC-MS/MS and in urine by DOAC Dipstick.

Official Title
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Study on the Pharmacokinetics and Point of Care Testing After a Single Dose of 150 mg Dabigatran, 20 mg Rivaroxaban, 5 mg Apixaban, and 60 mg Edoxaban in Healthy Male Subjects

Conditions
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Anticoagulant Therapy

Intervention / Treatment
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* Drug: Apixaban 5 MG Tab
* Drug: Dabigatran 150 MG Tab
* Drug: Edoxaban 60Mg Tab
* Drug: Rivaroxaban 20 MG Tab


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Fully signed and dated written informed consent Age >18 years healthy Exclusion Criteria: Patients not able to provide urine samples. Patients not able to understand the informed consent or severe mentally disabled. Patients in the end-stage of a severe disease.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Apixaban<br>Volunteers receive one oral dose of 5mg Apxiaban followed by sequential blood and urine sampling over 72 hours During the study liquid-chromatography mass-spectrometry analysis is performed in plasma and urine and DOAC Dipstick in urine. Biological and clinical safety parameters are measured. | Drug: Apixaban 5 MG Tab<br>* oral intake<br>* Other names: Edoxaban, Dabigatran, rivaroxaban;|
| Active Comparator: Dabigatran<br>Volunteers receive one oral dose of 150mg Dabigatran followed by sequential blood and urine sampling over 72 hours During the study liquid-chromatography mass-spectrometry analysis is performed in plasma and urine and DOAC Dipstick in urine. Biological and clinical safety parameters are measured. | Drug: Dabigatran 150 MG Tab<br>* oral intake<br>* Other names: Apixaban, Edoxaban, Rivaroxaban;|
| Active Comparator: Edoxaban<br>Volunteers receive one oral dose of 60mg Edoxaban followed by sequential blood and urine sampling over 72 hours During the study liquid-chromatography mass-spectrometry analysis is performed in plasma and urine and DOAC Dipstick in urine. Biological and clinical safety parameters are measured. | Drug: Edoxaban 60Mg Tab<br>* oral intake<br>* Other names: Apixaban, Dabigatran, Rivaroxaban;|
| Active Comparator: Rivaroxaban<br>Volunteers receive one oral dose of 20mg Rivaroxaban followed by sequential blood and urine sampling over 72 hours During the study liquid-chromatography mass-spectrometry analysis is performed in plasma and urine and DOAC Dipstick in urine. Biological and clinical safety parameters are measured. | Drug: Rivaroxaban 20 MG Tab<br>* oral intake<br>* Other names: Apixaban, Edoxaban, Dabigatran;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Accuracy and specificity of the DOAC Dipstick compare to LC-MSMS | Assess the accuracy and specificity of the IVD for oral direct factor Xa and thrombin inhibitors from urine samples of patients True positive and true negative rate of the point of care test (POCT) by comparison with the results obtained by bioanalytical quantification | up to 6 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Comparison of qualitative POCT with quantitative LC-MS/MS | Comparison of qualitative POCT with quantitative LC-MS/MS Investigator readings of POCT test results as compared to LC-MS/MS | up to 6 months | 
| Questionnaire on handling and usability | Specific questions to be answered using Lickert scale by personal performing the test | up to 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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anticoagulant, direct oral anticoagulant, apixaban, edoxaban, rivaroxaban, dabigatran, coagulation, point of care method