Clinical trial NCT02368314: A Safety and Efficacy Study of BCD-080 Compared to Clexan for Deep Vein Thrombosis Prophylaxis at Orthopedic Surgeries
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Deep Vein Thrombosis
Keywords: Deep vein thrombosis
Prophylaxis
Sodium enoxaparin
Lead sponsor: Biocad
Sponsor class: INDUSTRY
First posted: 2015-02-23
Enrollment: 124
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: 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: 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).

Eligibility criteria: Inclusion Criteria:

1. Written informed consent
2. Age ≥18 years and age ≤80 years
3. Women body mass 50-110kg, men body mass 57-110 kg inclusive
4. Patients who are planned for hip or knee replacement
5. 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
6. Ability of the patient, in the opinion of the investigator, to meet the Protocol requirements.

Exclusion Criteria:

1. 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
2. Conditions and diseases in which there is a high risk of bleeding: cerebral aneurysm or aortic dissection, hemorrhagic stroke (including in history)
3. Intractable hemorrhage
4. 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
5. Gastric or duodenal ulcer or other erosive and ulcerative lesions of gastrointestinal tract
6. Recent ischemic stroke
7. 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
8. Diabetic or hemorrhagic retinopathy
9. Decompensated diabetes mellitus, diabetes mellitus complications
10. Recent delivery (during last 90 days)
11. Bacterial endocarditis (acute or subacute)
12. Pericarditis and pericardial effusion
13. Renal and/or hepatic insufficiency
14. Intrauterine contraception
15. Surgeries or injuries of brain/spinal cord, spine, eyes, and major surgeries and injuries within 90 days prior to randomization)
16. Spinal surgeries or its deformation in history of patients who are planned for epidural/spinal anesthesia
17. Active liver diseases
18. Anamnestic information about alcoholism, addiction or drug abuse over the last year
19. Contraindications to surgeries
20. Hemoglobin \<100 g/l
21. Platelet count \<100х10\*9/l
22. Creatine clearance \<30 ml/min
23. Biochemical blood assay indexes: AST/ALT \> UNLх3; total bilirubin \> UNLх1,5 (unless other causal factors provided, such as Gilbert's syndrome)
24. 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.)
25. The use of dextrans or fibrinolytic therapy or other drugs affecting hemostasis;
26. 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)
27. Impossibility of contrast venography: contrast allergy, inability to install an intravenous catheter, etc
28. Pregnancy, lactation period
29. Donation of 450 ml or more of blood or plasma within 60 calendar days before inclusion enrolment
30. Participation in clinical trials no less than 30 days before enrolment into this study or previous participation in this clinical study.

Primary outcomes:
measure: Frequency of DVT.
timeFrame: During the treatment period (14 days)
measure: Frequency of Symptomatic Nonlethal Thromboembolia of the Pulmonary Artery (PATE)
timeFrame: During the treatment period (14 days)
measure: Frequency of Venous Thromboembolism Death
timeFrame: During the treatment period (14 days)
Secondary outcomes:
measure: Frequency of DTV
timeFrame: During the treatment period (14 days) and follow-up period (till 60-th day)
measure: Frequency of Proximal DVT
timeFrame: During the treatment period (14 days) and follow-up period (till 60-th day)
measure: Frequency of Distal DVT
timeFrame: During the treatment period (14 days) and follow-up period (till 60-th day)
measure: Frequency of Symptomatic Nonlethal PATE
timeFrame: During the treatment period (14 days) and follow-up period (till 60-th day)
measure: Frequency of Venous Thromboembolism Death
timeFrame: During the treatment period (14 days) and follow-up period (till 60-th day)
measure: Frequency of Death From Other Causes
timeFrame: During the treatment period (14 days) and follow-up period (till 60-th day)
measure: Frequency of Venous Thromboembolism (PATE and/or DTV)
timeFrame: During the treatment period (14 days) and follow-up period (till 60-th day)
measure: Frequency of "Big" and Clinically Significant "Small" Bleedings
timeFrame: During the treatment period (14 days)
measure: Frequency of "Big" Bleedings
timeFrame: During the treatment period (14 days)
measure: Frequency of Clinically Significant "Small" Bleedings
timeFrame: During the treatment period (14 days)
measure: Frequency of Clinically Significant Bleedings
timeFrame: During the treatment period (14 days)
measure: Frequency of Other "Small" Bleedings
timeFrame: During the treatment period (14 days)
measure: Frequency of All Bleedings
timeFrame: During the treatment period (14 days)
measure: Frequency of Heparin Induced Thrombocytopenia
timeFrame: During the treatment period (14 days)
measure: Frequency of Strokes, Myocardial Infarction, Unstable Angina and Cardiovascular Death
timeFrame: During the treatment period (14 days) and follow-up period (till 60-th day)
measure: Frequency of Other AE SAE
timeFrame: During the treatment period (14 days) and follow-up period (till 60-th day)
Other outcomes:
Locations:
city: Chelyabinsk
country: Russian Federation
facility: Railroad Clinical Hospital at the station Chelyabinsk
Study officials:
affiliation: Railroad Clinical Hospital at the station Chelyabinsk, Chelyabinsk, Russia
name: Ashot Agahanyan, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Railroad Clinical Hospital at the station Samara, Samara, Russia
name: Pavel Andreev, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: State budget institution of further education "Kazan State Medical Academy" the Ministry of Health of the Russian Federation
name: Ildar Ahtyamov, Professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Nizhny Novgorod Research Institute of Traumatology and Orthopedics of Public Health Ministry of Russian Federation
name: Valery Zagrekov, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Treatment and rehabilitation center of Public Health Ministry of Russian Federation, Moscow
name: Maxim Lucenko, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: State Institution "Republican Scientific and Practical Centre for Traumatology and Orthopedics" of the Ministry of Health of the Republic of Belarus
name: Alexander Sitnik, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References: