Arthroplasty, Replacement, Hip, Arthroplasty, Replacement, Knee, Prevention, Venous Thromboembolism (VTE)
Conditions
Brief summary
This clinical study aims to evaluate the efficacy and safety of the anticoagulant Dimolegin® compared to low molecular weight heparin (Clexane®) for the prevention of venous thromboembolic events (VTE) in patients undergoing major joint (hip or knee) replacement surgery. The study will assess the incidence of VTE, VTE-related mortality, and all-cause mortality during different follow-up periods in both treatment groups. Additionally, the study will evaluate the frequency of bleeding events and the incidence, number, and characteristics of all adverse events associated with Dimolegin® and Clexane® therapy.
Interventions
Subgroup 2A (Hip Arthroplasty): Patients undergoing total hip arthroplasty will receive Clexane® subcutaneously administered 12±1 hours before surgery starting 6-10 hours after surgery everyday for 35±2 days. Subgroup 2B (Knee Arthroplasty): Patients undergoing total knee arthroplasty will receive Clexane® subcutaneously administered 12±1 hours before surgery everyday for 14±1 days.
DRUGDimolegin
Subgroup 1A (Hip Arthroplasty): Patients undergoing total hip arthroplasty will receive Dimolegin® starting 6-10 hours after surgery everyday for 35±2 days. Subgroup 1B (Knee Arthroplasty): Patients undergoing total knee arthroplasty will receive Dimolegin® starting 6-10 hours after surgery everyday for 14±1 days.
DRUGDimolegin placebo
Subgroup 2A (Hip Arthroplasty): Patients undergoing total hip arthroplasty will receive placebo Dimolegin® starting 6-10 hours after surgery everyday for 35±2 days. Subgroup 2B (Knee Arthroplasty): Patients undergoing total knee arthroplasty will receive placebo Dimolegin® starting 6-10 hours after surgery everyday for 14±1 days.
DRUGSodium enoxaparine placebo
Subgroup 1A (Hip Arthroplasty): Patients undergoing total hip arthroplasty will receive palcebo Clexane® subcutaneously administered 12±1 hours before surgery starting 6-10 hours after surgery everyday for 35±2 days. Subgroup 2B (Knee Arthroplasty): Patients undergoing total knee arthroplasty will receive placebo Clexane® subcutaneously administered 12±1 hours before surgery everyday for 14±1 days.
Sponsors
Avexima Diol LLC
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Men and women between the ages of 18 and 80. * Patients scheduled for unilateral elective total hip or knee arthroplasty. * The patient's voluntary informed consent. * Negative pregnancy test result (for female patients with preserved reproductive potential). * Patients with reproductive potential should agree to use methods of contraception according to the protocol.
Exclusion criteria
* Surgery for an acute fracture (\<4 weeks). * Revision or extraction arthroplasty. * Septic arthritis. * The only lower limb. * Increased risk of thrombosis. * Active bleeding or increased risk of bleeding. * Current coagulopathy (patient's or his relative's) or congenital thrombophilia. * Collection of at least one volume unit of donated blood (≥ 450 ml) or blood transfusion during the previous 12 weeks. * Surgery or injury during the last 90 days. * Diseases of the digestive system that may disrupt the absorption of the study drug. * Significant cardiovascular diseases currently or within 6 months prior to screening. * Active liver or biliary tract diseases. * Creatinine clearance, calculated according to the Cockcroft-Gault formula, less than 30 ml/min. * Positive test result for HIV, syphilis, hepatitis B and C markers. * The development of trophic disorders of the lower extremities that are not amenable to drug treatment. * Any condition in which, in the opinion of the researcher, surgical intervention or the use of anticoagulants is contraindicated. * Body mass index is less than 18.5 or more than 40 kg/m2. * Body weight for women is less than 45 kg, for men less than 57 kg and above 130 kg for both. * Systolic blood pressure \> 180 mmHg and/or diastolic blood pressure \>110 mmHg. * Hemoglobin \< 105 g/l in women or \< 115 g/l in men. * Abnormal results aboratory parameters of the coagulation system (platelets, APTT, prothrombin time, INR) beyond the limits of normal values. * An increase in ALT or ACT ≥ 2 times from the upper limit of normal (ULN) or total bilirubin ≥ 1.5 times from ULN. * Hypersensitivity or contraindications to the administration of Dimolegin®, enoxaparin sodium, unfractionated heparin or warfarin. * The need for constant use of parenteral or oral anticoagulants. * The need for continuous use of antiplatelet drugs, which cannot be discontinued at least 4 days before the start of the investigational therapy. * Systemic therapy with drugs with strong inducers and inhibitors of CYP3A4 and P-glycoprotein, which cannot be discontinued at least 7 days before the start of the investigational therapy. * Pregnant or breast-feeding women. * Participation in another clinical trial currently or within 90 days prior to screening. * Affiliation to a research center, Sponsor, or contractual research organization. * Inability to read or write; unwillingness to understand and follow the procedures of the study protocol; non-compliance with the study therapy or procedures.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Composite endpoint i.e.: confirmed symptomatic DVT, asymptomatic DVT, non fatal PE, death of all causes | up to the follow-up visit (28±2 days after the end of therapy) |
Secondary
| Measure | Time frame |
|---|---|
| Switching to other anticoagulant therapy | up to the follow-up visit (28±2 days after the end of therapy) |
| Incidence of DVT (proximal, distal) | up to the follow-up visit (28±2 days after the end of therapy) |
| Incidence of non fatal PE | up to the follow-up visit (28±2 days after the end of therapy) |
| Composite endpoint i.e.: confirmed symptomatic DVT, asymptomatic DVT, non fatal PE, death due to thrombosis | up to the follow-up visit (28±2 days after the end of therapy) |
| Death due to VTE | up to the follow-up visit (28±2 days after the end of therapy) |
| Death of all causes | up to the end of therapy (for subgroup A - up to 14±1 days, for subgroup B - up to 35±2 days) |
| Incidence of symptomatic VTE | up to the follow-up visit (28±2 days after the end of therapy) |
Countries
Russia
Outcome results
None listed