Prevention of venous thromboembolism (VTE) in patients undergoing high VTE-risk knee surgery MedDRA version: 18.0 Level: LLT Classification code 10049909 Term: Venous thromboembolism prophylaxis System Organ Class: 100000004865
Conditions
Interventions
Product Name: Enoxaparin Sodium 40, 40 mg/0.4 ml, solution for injection
Pharmaceutical Form: Solution for injection in pre-filled syringe
INN or Proposed INN: ENOXAPARIN SODIUM
CAS Number: 9041-08-1
Sponsors
SciencePharma spólka z ograniczona odpowiedzialnoscia sp. k.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Caucasian male or female patients scheduled to undergo elective, unilateral major knee surgery, including patients requiring a revision of at least one component of a previously implanted total-knee prosthesis, eligible for 14 days prophylaxis against VTE with enoxaparin; 2. 18 years of age or older; 3. Body weight > 45 kg in females and > 57 kg in males; 4. Patients capable of understanding and following the study procedures, who will give their Informed Consent in a written form before any study qualification procedures begin. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 250
Exclusion criteria
Exclusion criteria: 1. Contraindications to surgery or any medical procedure required by the type of surgery (e.g. type of anaesthesia, urinary catherization if required etc.); 2. Contraindications to enoxaparin treatment in accordance with Clexane SmPC: • acute bacterial endocarditis; • active major bleeding; • conditions with a high risk of uncontrolled haemorrhage (e.g. recent haemorrhagic stroke); • active gastric or duodenal ulceration; • hypersensitivity to either enoxaparin sodium, heparin or its derivatives including other low molecular weight heparins; 3. History of immune-mediated heparin-induced thrombocytopenia (HIT type II) and/or thromboembolism (HITT); 4. Known any bleeding diathesis; 5. Known inherited thrombophilic disorder such as the factor V Leiden or prothrombin gene mutations or deficiencies of antithrombin, protein C, or protein S; 6. Abnormal results of blood coagulation tests (activated partial thromboplastin time (aPTT), prothrombin time (PT), International Normalized Ratio (INR)); 7. Anaemia (HGB 400 000/mm3), also if in history; 10. History of intracerebral, intraocular, gastrointestinal or urogenital bleeding, or active gastric or duodenal ulceration, within 6 months prior to randomization; 11. History of major surgery (invasive medical procedures involving tissues incision, requiring general or intrathecal anesthesia, access into the cavities of the body, associated with significant risk of major bleeding or in which the life of a patient is at stake, e.g. cardiac surgery, neurosurgery, ophthalmic surgery, abdominal surgery) within 3 months prior to randomization; 12. History of major trauma (defined as tissue, organ or large area of the body injury due to the action of mechanical, thermal, chemical or electrical factor etc.) within 3 months prior to randomization; 13. History of any thrombolytic or fibrynolysis inhibitor or anticoagulant use (except for heparins) within 4 weeks prior to randomization; 14. History of any heparin use within 100 days prior to randomization; 15. History of any antiplatelet use within 5 days prior to randomization; 16. Uncontrolled hypertension defined as systolic blood pressure > 180 mmHg or diastolic blood pressure > 110 mmHg at screening or at any time within 3 months prior to randomization; 17. Hyperkalemia; 18. History of deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction, cerebrovascular accident (CVA), or transient ischemic attack (TIA), within 6 months prior to randomization; 19. Severe cardiac failure (NYHA III-IV); 20. Unstable angina pectoris; 21. Known liver disease with aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels more than three times the upper limit of the normal range; 22. Known renal disease (calculated creatinine clearance 14 days) anticoagulation; 27. Severe peripheral vascular disease with ulceration or amputation; 28. Any confirmed or suspected acute hepatitis; 29. Pregnancy or lactation period in females; 30. Severe subjects who are known or suspected to be drug depend
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To prove the non-inferiority of the test IMP to the reference IMP regarding the incidence of patients with any bleeding events until 24 hours after trial therapy discontinuation.;Secondary Objective: To compare the test IMP to the reference IMP regarding: 1. Major bleeding events; 2. Clinically-relevant non-major bleeding events; 3. Other bleeding events; 4. Incidence of proximal DVT (asymptomatic and symptomatic); 5. Incidence of distal DVT (symptomatic); 6. Incidence of symptomatic non-fatal PE; 7. VTE-related death; 8. Composite of proximal asymptomatic and symptomatic DVT, distal symptomatic DVT, symptomatic non-fatal PE and VTE-related death; 9. Any adverse events (AE), including brain stroke, myocardial infarction, unstable angina, cardiovascular death; with selection of those related to IMPs; 10. Treatment discontinuation rate due to adverse events; 11. Death from all causes; 12. Incidence of immune-mediated heparin-induced thrombocytopenia (HIT type II) and/or thromboembolism (HITT). Other parameters related to surgery (e.g. peri- and post-operative blood loss, requirement for blood transfusion) will be recorded. ;Primary end point(s): Incidence of patients with any bleeding events until 24 hours after trial therapy discontinuation.;Timepoint(s) of evaluation of this end point: On day 15-16 of the study (after the 14-day treatment period) | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): To compare the test IMP to the reference IMP regarding: 1. Major bleeding events; 2. Clinically-relevant non-major bleeding events; 3. Other bleeding events; 4. Incidence of proximal DVT (asymptomatic and symptomatic); 5. Incidence of distal DVT (symptomatic); 6. Incidence of symptomatic non-fatal PE; 7. VTE-related death; 8. Composite of proximal asymptomatic and symptomatic DVT, distal symptomatic DVT, symptomatic non-fatal PE and VTE-related death; 9. Any adverse events (AE), including brain stroke, myocardial infarction, unstable angina, cardiovascular death; with selection of those related to IMPs; 10. Treatment discontinuation rate due to adverse events; 11. Death from all causes; 12. Incidence of immune-mediated heparin-induced thrombocytopenia (HIT type II) and/or thromboembolism (HITT). Other parameters related to surgery (e.g. peri- and post-operative blood loss, requirement for blood transfusion) will be recorded.;Timepoint(s) of evaluation of this end point: On day 15-16 of the study (after the 14-day treatment period) | — |
Countries
Poland
Contacts
Public ContactCoordinating Investigator
Jaroslaw Ucieklak, MD, PhD
Outcome results
None listed