Safety and Efficacy of TeaRx Xa Factor Direct Inhibitor Versus Enoxaparin as a Venous Thromboembolic Events (VTE) Prevention Following Total Knee Replacement

Study Overview
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Brief Summary
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To evaluate influence of therapy on the following efficacy and safety parameters in different TeaRx dose groups and Enoxaparin group: Total venous thromboembolic events (VTE), which includes confirmed deep venous thrombosis (DVT), nonfatal pulmonary embolism (PE), and total mortality Incidence of DVT (total, proximal, distal) Incidence of nonfatal PE Incidence of symptomatic VTE (DVT, PE) VTE caused mortality Non-VTE caused mortality Incidence of all hemorrhagic complications Incidence of major and clinically relevant non-major bleeding Adverse events (AEs) and serious adverse events (SAEs) from subject complaints, physical examination, vital signs, laboratory results

Official Title
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A Multicenter, Randomized, Pilot, Dose-Ranging Clinical Study to Evaluate Safety and Efficacy of TeaRx Xa Factor Direct Inhibitor Versus Enoxaparin as a Venous Thromboembolic Events (VTE) Prevention Following Total Knee Replacement

Conditions
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Total Knee Replacement

Intervention / Treatment
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* Drug: TeaRx
* Drug: Enoxaparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Male or female, age ≥ 18 years; Planned total knee replacement surgery; Signed informed consent form; Willing to comply with the protocol; Willing to use adequate contraception during the trial. Exclusion Criteria: Surgery for acute fracture 4 weeks before screening; history of septic inflammation in the joint; prosthesis revision or one leg missing History of venous thrombosis of any location or PE History of heparin induced thrombocytopenia or other thrombocytopathy; hemorrhagic diathesis History of evident coagulopathy or in a relative Congenital thrombophilia Bleeding within 6 months of screening; increased risk of bleeding BMI less than 18,5 or more than 40 kg/m2 Systolic BP > 180 mmHg and/or diastolic BP > 110 mmHg registered twice within 15-30 minutes Hb ≤ 10.5 g/dL in female or ≤ 11.5 g/dL in male Platelets < 100 000/mm3 Clinical significant abnormalities of APTT and/or INR GFR < 30 ml/min/1.73 m2 ALT or AST ≥ 2 x ULN or total bilirubin ≥1,5 x ULN

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
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: TeaRx 50 mg<br>TeaRx: 50 mg per day PO (active 25 mg + placebo 50 mg every 12 hours) during 12 days (±2 days) | Drug: TeaRx<br> <br> * Other names: TeaRxaban;|
| Experimental: TeaRx 100 mg<br>TeaRx: 100 mg per day PO (placebo 25 mg + active 50 mg every 12 hours) during 12 days (±2 days) | Drug: TeaRx<br> <br> * Other names: TeaRxaban;|
| Experimental: TeaRx 150 mg<br>TeaRx: 150 mg per day PO (active 25 mg + active 50 mg every 12 hours) during 12 days (±2 days) | Drug: TeaRx<br> <br> * Other names: TeaRxaban;|
| Active Comparator: Enoxaparin<br>Enoxaparin 40 mg subcutaneous per day (24 hours interval) during 12 days (±2 days) | 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 |
| --- | --- | --- |
| Incidence of deep venous thrombosis (DVT) (efficacy of the selected TeaRx dose) |  | 6 weeks following total knee replacement | 
| Incidence of nonfatal pulmonary embolism (PE) (efficacy of the selected TeaRx dose) |  | 6 weeks following total knee replacement | 
| Incidence of symptomatic venous thromboembolic events (DVT, PE) (efficacy of the selected TeaRx dose) |  | 6 weeks following total knee replacement | 
| venous thromboembolic events (VTE) caused mortality (efficacy of the selected TeaRx dose) |  | 6 weeks following total knee replacement | 
| Non-VTE caused mortality (efficacy of the selected TeaRx dose) |  | 6 weeks following total knee replacement | 
| AEs and SAEs from subject complaints, physical examination, vital signs, laboratory results (efficacy of the selected TeaRx dose) |  | 6 weeks following total knee replacement | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of bleeding (safety of selected TeaRx dose) | major and clinically relevant non-major bleeding | 6 weeks following total knee replacement |