Absorption of Rivaroxaban in Patients With Cervical Spinal Cord Injury

Study Overview
=================
Brief Summary
-----------------
The primary objective of this study is to investigate the pharmacokinetic and -dynamic properties of rivaroxaban after oral administration in cervical spinal cord injury (SCI) individuals. The secondary objective of this study is to determine the steady-state rivaroxaban activity in cervical SCI individuals under long-term therapy. Primary Objective In-house patients will be informed concerning the study and informed consent will be collected. During the screening day, in- / exclusion criteria will be assessed and a blood samples will be taken for assessing haematology, clinical chemistry and coagulation parameters. Furthermore, the evaluation day will be scheduled. On the evaluation day, in- / exclusion criteria will be re-assessed. A venous catheter will be introduced into a forearm or lower leg of each participant for the collection of blood at the specified time points. Skin inspection for subcutaneous bleeding will be performed and vital signs will be recorded. A blood sample will be taken for assessing haematology, clinical chemistry and coagulation parameters. Single administration of oral rivaroxaban in the form of Xarelto® 10mg tablets (Bayer Schering Pharma, Berlin, Germany). Rivaroxaban concentrations will be determined from plasma samples taken before, 30min after and 1, 2, 3, 4, 5, 6, 8, 12, 24 hours after rivaroxaban administration. Rivaroxaban activity will be determined from plasma samples taken before, 30min after and 1, 2, 3, 4, 5, 6, 8, 12, 24 hours after rivaroxaban administration using a factor Xa inhibition test and measuring prothrombin time (PT) and activated partial thromboplastin time (aPTT). Skin inspection for subcutaneous bleeding and measurements of vital signs will be performed 30min and 1, 2, 3, 4, 5, 6, 8, 12 and 24 hours after rivaroxaban administration. Secondary Objective Patients under long-term rivaroxaban therapy will be recruited during their annual check-up visit at the Swiss Paraplegic Centre. In- / exclusion criteria will be assessed, and the patients will be informed concerning the study and informed consent will be collected. Blood samples will be taken for assessing haematology, clinical chemistry and coagulation parameters, and skin inspection for subcutaneous bleeding and measurements of vital signs will be performed. A blood sample (4.3ml citrated venous blood) will be taken for assessing the primary and secondary outcome parameters.

Official Title
-----------------
Prospective, Non-randomized, Open-label, Mono-centric, Cohort Study on the Absorption of Oral Rivaroxaban in Patients With a Cervical Spinal Cord Injury

Conditions
-----------------
Spinal Cord Injuries, Thromboembolism

Intervention / Treatment
-----------------
* Drug: Rivaroxaban Oral Tablet


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Motor complete tetraplegia for at least 3 months Age from 18 to 74 years Body mass index (BMI) from 18 to 35kg/m2 Informed consent as documented by signature Exclusion Criteria: Any anti-coagulation therapy (apart from rivaroxaban for second objective) Hypersensitivity or allergy to factor Xa inhibitors Acute bacterial endocarditis Bleeding disorder Clinically relevant active bleeding Gastrointestinal ulcer or tumor Hepatic dysfunction with increased bleeding risk Renal failure / patients undergoing dialysis Pregnancy and breast feeding Gastrectomy, biliopancreatic diversion, resection or re-routing of small intestines Feeding tube Recent blood donation Abnormalities of laboratory values: alanine-aminotransferase (ALAT), aspartate-aminotransferase (ASAT), gamma-glutamyl transferase (gammaGT), alkalic phosphatase (AP), bilirubin, amylase, lipase, cystatin C, creatinine, white blood cell count, haemoglobin, platelet count, prothrombin time, aPTT, fibrinogen, thrombin time, factors II,V,VII and X Use of therapeutic or recreational drugs influencing plasmatic coagulation

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 74 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Other
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: rivaroxaban<br>Rivaroxaban Oral Tablet | Drug: Rivaroxaban Oral Tablet<br>* oral application of Xarelto<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| rivaroxaban plasma level |  | before drug administration and 30min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h and 24h after drug administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| inhibition of factor XII |  | before drug administration and 30min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h and 24h after drug administration | 
| prothrombin time |  | before drug administration and 30min, 1h, 2h, 3h, 4h, 5h, 6h, 8h, 12h and 24h after drug administration |