PK of Rivaroxaban in Bariatric Patients - Extension

Study Overview
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Brief Summary
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Aim of this clinical Trial is the assessment of rivaroxaban PK/PD parameters in patients 6-8 months after bariatric surgery

Detailed Description
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Weight loss after bariatric surgery can putatively alter drug disposition of rivaroxaban. This may be due to an altered intestinal adaptations several months after the surgical procedure. The aim of this clinical trial is to investigate pharmacokinetic and pharmacodynamic parameters after single application of 10 mg rivaroxaban in patients with prior bariatric intervention (Roux-en-y-gastric bypass or sleeve gastrectomy 6-8 months ago). PK/PD parameters will be assessed during 12 hours after application of rivaroxaban.

Official Title
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Pharmacokinetics and Pharmacodynamics of Single Doses of Rivaroxaban in Obesity Patients Before and After Bariatric Surgery - The Extension Study

Conditions
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Prophylaxis of Venous Thromboembolism

Intervention / Treatment
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* Drug: Rivaroxaban 10 mg


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with past elective bariatric surgery (Roux-en-Y gastric bypass surgery or sleeve gastrectomy 6-8 months ago) Patient aged 18 years and older BMI ≥ 35 kg/m2 Women of child-bearing age: Willingness of using a double barrier contraception method during the study Written, informed consent Exclusion Criteria: Intake of oral anticoagulants (phenprocoumon, acenocoumarol, dabigatran, etexilate, apixaban etc.) 4 weeks prior to inclusion in the study Application of parenteral anticoagulants (unfractionated heparin, low molecular weight heparins, heparin derivates (fondaparinux etc.) 4 weeks prior to inclusion in the study Pharmacologic platelet inhibition 4 weeks prior to inclusion in the study Known coagulation disorders (e.g. Willebrand's disease, haemophilia) Evidence for deep vein thrombosis or pulmonary embolism in the personal history or in the history of first degree relatives Medical condition that is associated with an increased risk for VTE, i.e. active cancer disease, lupus erythematodes chronic inflammatory bowel disease Active, clinically significant bleeding Congenital or acquired bleeding disorder Uncontrolled severe hypertension Active gastrointestinal disease that can potentially lead to bleeding disorder: oesophagitis, gastritis, gastroesophageal reflux disease, chronic inflammatory bowel disease Vascular retinopathy Bronchiectasis or history of pulmonary bleeding Prior stroke or TIA Hereditary galactose intolerance, Lapp lactase deficiency, glucose-lactose malabsorption Severe renal impairment with a creatinine clearance (GFR) of < 30ml/min Positive pregnancy test, pregnancy or nursing women High risk of bleeding (e.g. active ulcerative gastrointestinal disease) Known intolerance of the study medication rivaroxaban Concomitant treatment with strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, lopinavir, ritonavir, indinavir) Concomitant treatment with an P-glycoprotein inhibitor and weak or moderate CYP3A4 inhibitor (e.g. erythromycin, azithromycin, diltiazem, verapamil, quinidine, ranolazine, dronedarone, amiodarone, felodipine)

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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Rivaroxaban Arm<br> | Drug: Rivaroxaban 10 mg<br>* At study month 7 (+/-1 month), patients receive at 8 a.m. a single dose of 10 mg rivaroxaban. Study specific blood tubes are sampled the same day at the indicated time points from T -1h to T 12h.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| AUC of rivaroxaban |  | 1 year | 
| Cmax of rivaroxaban |  | 1 year | 
| Tmax of rivaroxaban |  | 1 year | 
| Prothrombin time (PT) |  | 1 year | 
| Activated partial thromboplastin time (aPTT) |  | 1 year | 
| Levels of Prothrombin fragment (F1+F2) |  | 1 year | 
| Levels of Thrombin-antithrombin-complexes (TAT) |  | 1 year | 
| Levels of D-Dimers |  | 1 year |