Evaluation of AVE5026 as Compared to Enoxaparin for the Prevention of Thromboembolism in Patients Undergoing Hip Fracture Surgery

Study Overview
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Brief Summary
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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 hip fracture surgery. The secondary objectives were to evaluate the safety of AVE5026 in patients undergoing hip fracture surgery, and to document AVE5026 exposure in this population.

Detailed Description
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Randomization had to take place just prior to 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 between 7 to 11 days after surgery.

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

Conditions
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Venous Thromboembolism

Intervention / Treatment
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* Drug: Enoxaparin sodium
* Drug: Semuloparin sodium
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Standard surgery for fracture of the upper third of the femur including femoral head and neck. Exclusion Criteria: Estimated time of injury/fracture > 24 hours before admission to hospital; Any major orthopedic surgery in the 3 months prior to study start; Multiple trauma affecting more than one organ system; 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, or pork products; 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<br>Semuloparin sodium 20 mg (10 mg if Severe Renal Impairment [SRI]) once daily for 7-10 days with an initial dose given 8 hours after surgery Placebo for Enoxaparin sodium prior to surgery according to local standard for Enoxaparin and 12 hours after surgery to maintain the blind | 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<br>* Other names: AVE5026;Drug: Placebo<br>* 0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml prefilled syringe strictly identical in appearance but without active component Subcutaneous injection<br>|
| Active Comparator: Enoxaparin<br>Enoxaparin sodium 40 mg (20 mg if Severe Renal Impairment [SRI]) once daily for 7-10 days with an initial dose given prior to or 12 hours after surgery according to local standard for Enoxaparin sodium Placebo for Semuloparin sodium 8 hours after surgery to maintain the blind | Drug: Enoxaparin sodium<br>* 0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe Subcutaneous injection<br>* Other names: Lovenox®;Drug: Placebo<br>* 0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml prefilled syringe strictly identical in appearance but without active component Subcutaneous injection<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Experienced Venous Thromboembolism Event [VTE] or All-cause Death | VTE included any Deep Vein Thrombosis [DVT] (proximal or distal, 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. | From randomization up to 10 days after surgery or the day of mandatory venography, whichever came first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Experienced Major VTE or All-cause Death | major VTE included any proximal DVT, symptomatic distal DVT and non-fatal PE as confirmed by the CIAC. | From randomization up to 10 days after surgery or the day of mandatory venography, whichever came first | 
| Percentage of Participants Who Experienced Clinically Relevant Bleedings | 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. | From first study drug injection up to 3 days after last study drug injection | 
| Percentage of Participants Who Required the Initiation of Curative Anticoagulant or Thrombolytic Treatment After VTE Assessment | 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. | From randomization up to 10 days after surgery or the day of mandatory venography, whichever came first | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hip fractures, Heparin Low-Molecular-Weight, Randomized Controlled Trial