Venous Thromboembolism
Conditions
Keywords
venous thromboprophylaxis, primary prevention, orthopedic surgery
Brief summary
The primary objective is to evaluate the efficacy of once daily (QD) subcutaneous (SC) injections of Semuloparin sodium (AVE5026) versus placebo for 3 additional weeks following an initial 7 to 10-day venous thromboprophylaxis with open-label AVE5026 in patients having undergone hip fracture surgery. The secondary objective is to evaluate the safety of extended AVE5026 administration.
Detailed description
The total duration of observation per participant is 56-63 days from surgery broken down as follows: * 7 to 10-day initial treatment period with open-label Semuloparin sodium; * Randomization; * 19 to 23-day double-blind treatment period with Semuloparin sodium or placebo; * 30-day follow-up period. Mandatory bilateral venography of the lower limbs is to be performed between 19 and 24 days after randomization.
Interventions
DRUGOpen-label Semuloparin sodium
0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe Subcutaneous injection once daily with an initial dose given 8 hours after surgery
0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml prefilled syringe strictly identical in appearance containing the same volume but without active component Subcutaneous injection once daily
0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe Subcutaneous injection once daily
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
* In the run-in phase: * Standard surgery for fracture of the upper third of the femur, including femoral head and neck * In the double-blind phase following the run-in phase: * Completion of the run-in phase without permanent treatment discontinuation
Exclusion criteria
* Any major orthopedic surgery within 3 months prior to enrolment; * Deep vein thrombosis or pulmonary embolism within the last 12 months, or known post-phlebitic syndrome; * High risk of bleeding; * Known hypersensitivity to heparins; * Any contraindication 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 Experience Venous Thromboembolism Events (VTE) or Death From Any Cause During the Extension Treatment Period | From randomization up to 24 days after randomization or the day of mandatory venography, whichever comes first | VTE include any 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 suspected VTE. All-cause deaths include fatal PE and deaths for other reason than PE. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experience Major VTE or Death From Any Cause | From randomization up to 24 days after randomization or the day of mandatory venography, whichever comes first | Major VTE include any proximal DVT, symptomatic distal DVT and non-fatal PE as confirmed by the CIAC. |
| Percentage of Participants Who Experience Clinically Relevant Bleedings During the Extension Treatment Period | From 1st study drug injection in the extension treatment period up to 3 days after last study drug injection | Bleedings are 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 health care professional); Non-clinically relevant bleeding. |
| Percentage of Participants Who Require the Initiation of Curative Anticoagulant or Thrombolytic Treatment After VTE Assessment During the Extension Treatment Period | From randomization up to 24 days after randomization or the day of mandatory venography, whichever comes first | Initiation of curative anticoagulant or thrombolytic treatment after VTE assessment is 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 |
|---|---|---|
| Overview of Reported Bleeding Adverse Event | From 1st study drug injection up to 3 days after last study drug injection | Analysis periods are defined as follows: * Initial treatment: time from the first study drug injection up to the first injection in the extension period or up to 3 days after the last injection if no extension treatment; * Extension treatment: time from first injection in the extension period up to 3 days after the last injection. |
| Overview of Deaths | From 1st study drug injection up to 3 days after last study drug injection | The same analysis periods as defined for the previous outcome measure are used. In addition deaths during the extension treatment period are 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). |
| Platelets Count: Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA) | From 1st study drug injection up to 3 days after last study drug injection | PCSA are abnormal values considered medically important by the Sponsor according to pre-defined criteria based on literature review. Threshold for platelets count was defined as \<100 Giga/L. The analysis periods as previously defined are used (see outcome measure 5). |
| Liver Function: Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA) | From 1st study drug injection up to 3 days after last study drug injection | Thresholds are defined as follows: * Alanine Aminotransferase \[ALT\] \>3 Upper Normal Limit \[ULN\]; * Total Bilirubin \[TB\] \>2 ULN; * ALT \>3 ULN and TB \>2 ULN; Cases with ALT \>3 ULN and TB \>2 ULN (not necessarily concomitant) are evaluated by a blinded independent adjudicator to determine if they met Hy's law criteria. The analysis periods as previously defined are used (see outcome measure 5). |
Countries
Belarus, Canada, Chile, China, Colombia, Egypt, India, Lithuania, Mexico, Peru, Russia, South Africa, South Korea, Turkey (Türkiye), Ukraine, United States
Outcome results
None listed