Evaluation of AVE5026 as Compared to Placebo for the Extended Prophylaxis of Venous Thromboembolism in Patients Having Undergone Hip Fracture Surgery

Study Overview
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Brief Summary
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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
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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.

Official Title
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A Multinational, Multicenter, Randomized, Double-Blind Study Comparing the Efficacy and Safety of AVE5026 With Placebo for the Extended Prevention of Venous Thromboembolism in Patients Having Undergone Hip Fracture Surgery

Conditions
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Venous Thromboembolism

Intervention / Treatment
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* Drug: Open-label Semuloparin sodium
* Drug: Placebo (for Semuloparin sodium)
* Drug: Semuloparin sodium


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Semuloparin extension treatment<br>Extension treatment with Semuloparin sodium 20 mg (10 mg if SRI) for 19-23 days following initial treatment with open-label Semuloparin 20 mg (10 mg if SRI) for 7-10 days. | Drug: Open-label Semuloparin sodium<br>* 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<br>* Other names: AVE5026;Drug: Semuloparin sodium<br>* 0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe Subcutaneous injection once daily<br>* Other names: AVE5026;|
| Placebo Comparator: Placebo extension treatment<br>Extension treatment with placebo (for Semuloparin sodium) for 19-23 days following initial treatment with open-label Semuloparin 20 mg (10 mg if SRI) for 7-10 days | Drug: Open-label Semuloparin sodium<br>* 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<br>* Other names: AVE5026;Drug: Placebo (for Semuloparin sodium)<br>* 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<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Experience Venous Thromboembolism Events (VTE) or Death From Any Cause During the Extension Treatment Period | 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. | From randomization up to 24 days after randomization or the day of mandatory venography, whichever comes first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Experience Major VTE or Death From Any Cause | Major VTE include any proximal DVT, symptomatic distal DVT and non-fatal PE as confirmed by the CIAC. | From randomization up to 24 days after randomization or the day of mandatory venography, whichever comes first | 
| Percentage of Participants Who Experience Clinically Relevant Bleedings During the Extension Treatment Period | 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. | From 1st study drug injection in the extension treatment period up to 3 days after last study drug injection | 
| Percentage of Participants Who Require the Initiation of Curative Anticoagulant or Thrombolytic Treatment After VTE Assessment During the Extension Treatment Period | 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. | From randomization up to 24 days after randomization or the day of mandatory venography, whichever comes first | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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venous thromboprophylaxis, primary prevention, orthopedic surgery