A Safety and Efficacy Study of BCD-080 Compared to Clexan for Deep Vein Thrombosis Prophylaxis at Orthopedic Surgeries

Study Overview
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Brief Summary
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The purpose of the study is to prove equivalence of efficacy and safety of BCD-080 and Clexan for deep vein thrombosis and embolism prophylaxis at orthopedic surgeries.

Detailed Description
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The study will include 116 patients who are planned for hip or knee replacement. Patients will randomized in 2 groups. 1-st group will receive BCD-080 at dose 30 mg every 12 hours during 14 days after surgery, 2-d group will receive Clexane at the same dose. Efficacy assessment will include frequency of deep vein thrombosis (DVT) (proximal and/or distal; symptomatic or asymptomatic), symptomatic nonlethal thromboembolia of the pulmonary artery (PATE) and venous thromboembolism death. Safety assessment will include frequency of big, small and other bleedings and frequency of heparin induced thrombocytopenia.The assessment of efficacy and safety parameters will be made during the treatment and follow-up period (till 60 day).

Official Title
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International Multicenter Randomized Double-blind Comparative Clinical Trial of Safety and Efficacy of BCD-080 (JSC BIOCAD, Russia) and Clexan® (Sanofi Aventis France, France) for Deep Vein Thrombosis Prophylaxis at Orthopedic Surgeries

Conditions
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Deep Vein Thrombosis

Intervention / Treatment
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* Drug: Sodium Enoxaparine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Written informed consent Age ≥18 years and age ≤80 years Women body mass 50-110kg, men body mass 57-110 kg inclusive Patients who are planned for hip or knee replacement Willingness of patients of both sexes and their sexual partners with preserved reproductive function to use reliable methods of contraception, starting from screening and up to 4 weeks after the last dose of the studied drug. This requirement does not apply to patients who underwent surgical sterilization. Reliable methods of contraception involves a 1-barrier method combined with one of the following: spermicides/oral contraceptive Ability of the patient, in the opinion of the investigator, to meet the Protocol requirements. Exclusion Criteria: Hypersensitivity to the components included in the formula of preparation BCD-080 (CJSC BIOCAD) Clexane (Sanofi-Avensis France, France) or medications of the same class Conditions and diseases in which there is a high risk of bleeding: cerebral aneurysm or aortic dissection, hemorrhagic stroke (including in history) Intractable hemorrhage History of documented diseases of blood coagulation (hemophilia A or B, Willebrand disease and other coagulopathies, idiopathic thrombocytopenic purpura, Heparin induced thrombocytopenia associated with thrombosis or without it, thrombohemorrhagic syndrome, etc.) in anamnesis and/or at the moment of examination Gastric or duodenal ulcer or other erosive and ulcerative lesions of gastrointestinal tract Recent ischemic stroke Uncontrolled severe hypertension; that is, all cases of hypertension, in which blood pressure decrease cannot be achieved with the use of combination of 3 antihypertensive drugs, compulsorily including a diuretic, and non-drug methods of correction (salt-free diet, graduated exercise); or if the results of two successive measurements of supine arterial blood pressure with an interval of 15-30 minutes, systolic blood pressure> 180 mm Hg. or diastolic blood pressure> 105 mm Hg Diabetic or hemorrhagic retinopathy Decompensated diabetes mellitus, diabetes mellitus complications Recent delivery (during last 90 days) Bacterial endocarditis (acute or subacute) Pericarditis and pericardial effusion Renal and/or hepatic insufficiency Intrauterine contraception Surgeries or injuries of brain/spinal cord, spine, eyes, and major surgeries and injuries within 90 days prior to randomization) Spinal surgeries or its deformation in history of patients who are planned for epidural/spinal anesthesia Active liver diseases Anamnestic information about alcoholism, addiction or drug abuse over the last year Contraindications to surgeries Hemoglobin <100 g/l Platelet count <100х10*9/l Creatine clearance <30 ml/min Biochemical blood assay indexes: AST/ALT > UNLх3; total bilirubin > UNLх1,5 (unless other causal factors provided, such as Gilbert's syndrome) Necessity for continued treatment with anticoagulants (except for planned under this study), antiaggregant and fibrinolytics (eg, patients with artificial cardiac valve, atrial fibrillation patients receiving warfarin, etc.) The use of dextrans or fibrinolytic therapy or other drugs affecting hemostasis; Necessity for use of systemic glucocorticosteroids and non-steroidal anti-inflammatory drugs (except for the use of the latter with the purpose of anaesthesia in the early postoperative period - during 3 days after the planned hip or knee replacement) Impossibility of contrast venography: contrast allergy, inability to install an intravenous catheter, etc Pregnancy, lactation period Donation of 450 ml or more of blood or plasma within 60 calendar days before inclusion enrolment Participation in clinical trials no less than 30 days before enrolment into this study or previous participation in this clinical study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 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: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: BCD-080<br>Sodium enoxaparine 40 mg (4 000 anti-Xa IU / 0,4 ml) at pre-filled syringe. Administration of BCD-080 30 mg (0,3 ml) every 12 hours during 14 days after surgery for preventing venous thromboembolic complications after surgery. | Drug: Sodium Enoxaparine<br>* 30 mg (0,3 ml), subcutaneously, twice a day (every 12 h).<br>* Other names: BCD-080 (Sodium Enoxaparine);|
| Active Comparator: Clexane<br>Sodium enoxaparine 40 mg (4 000 anti-Xa IU / 0,4 ml) at pre-filled syringe. Administration of Clexane 30 mg (0,3 ml) every 12 hours during 14 days after surgery for preventing venous thromboembolic complications after surgery/ | Drug: Sodium Enoxaparine<br>* 30 mg (0,3 ml), subcutaneously, twice a day (every 12 h).<br>* Other names: BCD-080 (Sodium Enoxaparine);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of DVT. | Frequency of deep vein thrombosis (DVT) (proximal and/or distal; symptomatic or asymptomatic). | During the treatment period (14 days) | 
| Frequency of Symptomatic Nonlethal Thromboembolia of the Pulmonary Artery (PATE) |  | During the treatment period (14 days) | 
| Frequency of Venous Thromboembolism Death |  | During the treatment period (14 days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Frequency of DTV | Frequency of DTV (proximal and/or distal; symptomatic or asymptomatic) | During the treatment period (14 days) and follow-up period (till 60-th day) | 
| Frequency of Proximal DVT | Frequency of proximal DVT (symptomatic or asymptomatic) | During the treatment period (14 days) and follow-up period (till 60-th day) | 
| Frequency of Distal DVT | Frequency of distal DVT (symptomatic or asymptomatic) | During the treatment period (14 days) and follow-up period (till 60-th day) | 
| Frequency of Symptomatic Nonlethal PATE |  | During the treatment period (14 days) and follow-up period (till 60-th day) | 
| Frequency of Venous Thromboembolism Death |  | During the treatment period (14 days) and follow-up period (till 60-th day) | 
| Frequency of Death From Other Causes |  | During the treatment period (14 days) and follow-up period (till 60-th day) | 
| Frequency of Venous Thromboembolism (PATE and/or DTV) |  | During the treatment period (14 days) and follow-up period (till 60-th day) | 
| Frequency of Big and Clinically Significant Small Bleedings |  | During the treatment period (14 days) | 
| Frequency of Big Bleedings |  | During the treatment period (14 days) | 
| Frequency of Clinically Significant Small Bleedings |  | During the treatment period (14 days) | 
| Frequency of Clinically Significant Bleedings |  | During the treatment period (14 days) | 
| Frequency of Other Small Bleedings |  | During the treatment period (14 days) | 
| Frequency of All Bleedings |  | During the treatment period (14 days) | 
| Frequency of Heparin Induced Thrombocytopenia |  | During the treatment period (14 days) | 
| Frequency of Strokes, Myocardial Infarction, Unstable Angina and Cardiovascular Death |  | During the treatment period (14 days) and follow-up period (till 60-th day) | 
| Frequency of Other AE SAE |  | During the treatment period (14 days) and follow-up period (till 60-th day) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Deep vein thrombosis, Prophylaxis, Sodium enoxaparin