Venous Thromboembolism
Conditions
Keywords
Prevention, Venous Thrombosis, Orthopedic Surgery
Brief summary
The primary objective was to demonstrate the dose-response of Semuloparin sodium (AVE5026) for the prevention of Venous Thromboembolism \[VTE\] in patients undergoing total knee replacement \[TKR\] surgery. Secondary objectives were to evaluate the safety (incidence of major bleeding) of AVE5026, to document the efficacy and safety of AVE5026 post-operative regimens, and to assess the pharmacokinetic parameters of AVE5026.
Detailed description
The randomization had to take place before the first study drug injection. The total duration of observation per participant was 27-33 days from surgery broken down as follows: * 4 to 10-day double-blind treatment period; * Follow-up period up to Day 30 ± 3 after surgery. Mandatory bilateral venography of the lower limbs had to be performed between 5 to 11 days after surgery.
Interventions
0.8 mL solution in Type I amber glass vials Subcutaneous injection
DRUGPlacebo (for Enoxaparin sodium)
0.4 mL solution in ready-to-use prefilled syringe strictly identical in appearance containing the same volume but without active component Subcutaneous injection
DRUGEnoxaparin sodium
0.4 mL solution in ready-to-use pre-filled syringe Subcutaneous injection
0.8 ml solution in type I amber glass vials strictly identical in appearance containing the same volume but without active component Subcutaneous injection
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patient scheduled to undergo elective total knee replacement or revision of a primary procedure performed ≥ 6 months prior to study entry.
Exclusion criteria
* Any major orthopedic surgery in the 3 months prior to study entry; * Clinical signs or symptoms of DVT or PE within the last 12 months or known post-phlebitic syndrome; * Known sensitivity to iodine or contrast dyes; * Recent stroke or myocardial infarction; * High risk of bleeding; * Treatment with other anti-thrombotic agents within 7 days prior to surgery; * Any contra-indication to Unfractionated Heparin or Low Molecular Weight Heparin; * Pregnant or nursing woman, or woman of childbearing potential who is not using an effective contraceptive method. The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Venous Thromboembolism Event (VTE) or VTE-related Death | From surgery to Day 11 or the day of mandatory venography, whichever came first | VTE included any Deep Vein Thrombosis \[DVT\] identified on mandatory venography of the lower limbs; symptomatic DVT and/or non-fatal pulmonary embolism \[PE\] before mandatory examination; VTE related deaths included fatal PE or deaths which could not be attributed to a documented cause and for which PE could not be ruled out. All events were to be confirmed by a Central Independent Adjudication Committee \[CIAC\] based on venographies, scheduled or unscheduled, and other available diagnostic tests (ultrasonography, ventilation/perfusion lung scan, pulmonary angiography, autopsy report, etc). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants Who Experienced Symptomatic VTE | From surgery up to Day 11 or the day of mandatory venography, whichever came first | Symptomatic VTE included: * suspected DVT confirmed by the CIAC based on compression ultrasonography or venography; * suspected PE confirmed by the CIAC based on perfusion/ventilation lung scan, pulmonary angiography or spiral computerized tomography. |
| Number of Participants Who Experienced DVT | From surgery up to Day 11 or the day of mandatory venography, whichever came first | — |
| Number of Participants Who Experienced Bleedings | From 1st study drug injection up to 3 days after last study drug injection (median duration of approximately 11 days) | Bleedings were centrally and blindly reviewed by the CIAC and classified as: * Major (fatal bleeding, bleeding that was retroperitoneal or intracranial or that involved any other critical organ (e.g. eye, adrenal gland, pericardium or spine), surgical site bleeding leading to intervention, non-surgical site bleeding requiring surgical intervention or with a bleeding index ≥2); * Minor (overt bleeding considered more than expected but not meeting the criteria for major bleeding); * Criteria for bleeding event not satisfied (not meeting the criteria for major or minor bleeding). |
| Number of Participants Who Required Initiation of Curative Anticoagulant or Thrombolytic Treatment After VTE Assessment | From surgery up to Day 11 or the day of mandatory venography, whichever came first | Initiation of curative anticoagulant or thrombolytic treatment after VTE assessment was defined from investigator's answers to questions asked after diagnostic tests for suspected VTE and/or the mandatory venography. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities [PCSA] | From 1st study drug injection up to 3 days after last study drug injection (median duration of approximately 11 days) | Thresholds were defined as follows: * Alanine Aminotransferase \[ALAT\] \>3 Upper Normal Limit \[ULN\]; * Total Bilirubin \[TB\] ≥34 μmol/L; * ALAT ≥3 ULN and TB ≥34 μmol/L. |
| Platelets Count: Number of Participants With Potentially Clinically Significant Abnormalities [PCSA] | From 1st study drug injection up to 3 days after last study drug injection (median duration of approximately 11 days) | PCSA are abnormal values considered medically important by the Sponsor according to predefined criteria based on literature review. Threshold for platelet counts was defined as \<100 Giga/L. |
| Number of Deaths | From 1st study drug injection up to 3 days after last study drug injection (median duration of approximately 11 days) | All deaths were centrally and blindly reviewed by the CIAC and classified as Fatal PE, PE not excluded, Fatal bleeding and Death not associated with VTE or bleeding based on relevant documentation (e.g. autopsy report). |
Countries
Argentina, Bulgaria, Chile, Colombia, Denmark, Finland, Greece, Malaysia, Mexico, Norway, Philippines, Poland, Portugal, Romania, Russia, Sweden, Taiwan, Thailand, Turkey (Türkiye)
Outcome results
None listed