Venous Thromboembolism
Conditions
Keywords
VTE prevention, Total Hip Replacement, Heparin Low-Molecular-Weight
Brief summary
The primary objective was to compare the efficacy of once daily \[q.d.\] subcutaneous \[s.c.\] injections of Semuloparin sodium (AVE5026) with q.d. s.c. injections of enoxaparin for the prevention of Venous Thromboembolic Events \[VTE\] in patients undergoing elective total hip replacement surgery. The secondary objectives were to evaluate the safety of AVE5026 in patients undergoing elective total hip replacement surgery, and to document AVE5026 exposure in this population.
Detailed description
Randomization had to take place just prior the first study drug injection (randomization ratio 1:1). The total duration of observation per participant was 35-42 days from surgery broken down as follows: * 7 to 10-day double-blind treatment period; * 28 to 35-day follow-up period. Mandatory bilateral venography of the lower limbs had to be performed 7 to 11 days after surgery.
Interventions
0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe Subcutaneous injection
DRUGEnoxaparin sodium
0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe Subcutaneous injection
DRUGPlacebo
0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe strictly identical in appearance but without active component Subcutaneous injection
Sponsors
Sanofi
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 No maximum
Healthy volunteers
No
Inclusion criteria
* Elective total hip replacement surgery or a revision of at least one component of a prosthesis implanted ≥ 6 months prior to study entry.
Exclusion criteria
* Any major orthopedic surgery in the 3 months prior to study start; * Deep vein thrombosis or pulmonary embolism within the last 12 months or known post-phlebitic syndrome; * High risk of bleeding; * Known allergy to heparin or enoxaparin; * Any contra-indications to the performance of venography; * End stage renal disease or patient on dialysis. 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 |
|---|---|---|
| Percentage of Participants Who Experienced Venous Thromboembolism Event [VTE] or Death From Any Cause | From randomization up to 10 days after surgery or the day of mandatory venography, whichever came first | VTE included any proximal or distal Deep Vein Thrombosis \[DVT\] (symptomatic or not) and non-fatal Pulmonary Embolism \[PE\] as confirmed by a Central Independent Adjudication Committee \[CIAC\] after review of mandatory bilateral venograms and diagnostic tests for VTE. All-cause deaths included fatal PE and deaths for other reason than PE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experienced Major VTE or All-cause Death | From randomization up to 10 days after surgery or the day of mandatory venography, whichever came first | major VTE included any proximal DVT, symptomatic distal DVT and nonfatal Pulmonary Embolism (PE) as confirmed by the CIAC. |
| Percentage of Participants Who Experienced Clinically Relevant Bleedings | From first study drug injection up to 3 days after last study drug injection | Bleedings were centrally and blindly reviewed by the CIAC and classified as: * major (fatal, in a critical area/organ, causing a post-operative drop in hemoglobin ≥2 g/dL or requiring post-operative transfusion ≥2 units of blood, leading to an invasive diagnostic or therapeutic intervention, or associated with circulatory decompensation); * clinically relevant non-major (skin hematoma or epistaxis requiring surgical/medical intervention/treatment, macroscopic hematuria, or overt bleeding requiring specific attention by healthcare professional); * Non-clinically relevant bleeding. |
| Percentage of Participants Who Required the Initiation of Curative Anticoagulant or Thrombolytic Treatment After VTE Assessment | From randomization up to 10 days after surgery or the day of mandatory venography, whichever came first | Initiation of curative anticoagulant or thrombolytic treatment after VTE assessment was defined from investigator's answer to the question was the subject treated for VTE? asked after the diagnostic tests for suspected VTE and after the mandatory venography. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Platelets Count: Percentage of Participants With Potentially Clinically Significant Abnormalities [PCSA] | From first study drug injection up to 3 days after last study drug injection | PCSA values 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. |
| Liver Function: Percentage of Participants With Potentially Clinically Significant Abnormalities [PCSA] | From first study drug injection up to 3 days after last study drug injection | Thresholds were defined as follows: * Alanine Aminotransferase \[ALAT\] \>3 Upper Normal Limit \[ULN\]; * Total Bilirubin \[TB\] \>2 ULN; * ALAT \>3 ULN and TB \>2 ULN; Cases with ALAT \>3 ULN and TB \>2 ULN (not necessarily concomitant) were evaluated by a blinded independent adjudicator to determine if they met Hy's law criteria. |
| Overview of deaths | From first study drug injection up to 3 days after last study drug injection | All deaths were centrally and blindly reviewed by the CIAC and classified as fatal PE, fatal bleeding, cardiovascular death or other based on relevant documentation (e.g. autopsy report). |
Countries
Argentina, Australia, Belarus, Canada, Chile, Colombia, Czechia, Denmark, Estonia, Finland, Germany, Greece, India, Italy, Mexico, Norway, Peru, Philippines, Poland, Romania, Russia, Slovakia, South Africa, Spain, Sweden, Taiwan, Thailand, Turkey (Türkiye), Ukraine, United States
Outcome results
None listed