Evaluation of AVE5026 as Compared to Enoxaparin for the Prevention of Venous Thromboembolism in Patients Undergoing Major Abdominal Surgery

Study Overview
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Brief Summary
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The primary objective is to compare the efficacy and safety 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 major abdominal surgery. The secondary objectives are to evaluate the safety of Semuloparin sodium (AVE5026) and to document Semuloparin sodium (AVE5026) exposure in this population.

Detailed Description
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Randomization has to take place prior to the surgery. The total duration of observation per participant is 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 has 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 Major Abdominal Surgery

Conditions
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Venous Thromboembolism

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient undergoing major abdominal surgery (open surgery under general anesthesia lasting more than 45 minutes in the peritoneal and/or retroperitoneal space and/or pelvis). Patient <60 years of age had to have one of the following additional risk factors for VTE: History of VTE, Obesity, Chronic Heart failure, Chronic Respiratory Failure, Inflammatory Bowel Disease, Cancer Surgery. Exclusion Criteria: Any major orthopedic or general surgery in the 3 months prior to study start; Clinical signs or symptoms of DVT or PE within the last 12 months or known post phlebitic syndrome; Any contra-indications to the performance of venography; High risk of bleeding; Known hypersensitivity to heparin or Enoxaparin sodium; End stage renal disease or patient on dialysis. The above information was 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 containing the same volume 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 containing the same volume 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 Experience Venous Thromboembolism Event (VTE) or All-cause Death | VTE includes 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 includes fatal PE and deaths for other reason than PE. | From randomization up to 10 days after surgery 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 All-cause Death | major VTE includes any proximal DVT, symptomatic distal DVT and non-fatal Pulmonary Embolism (PE) as as confirmed by the CIAC. | From randomization up to 10 days after surgery or the day of mandatory venography, whichever comes first | 
| Percentage of Participants Who Experience Clinically Relevant Bleedings (major and clinically relevant non-major bleedings ) | 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); Nonclinically relevant bleeding. | From 1st study drug injection up to 3 days after last study drug injection | 
| Percentage of Participants requiring 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 comes first | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Digestive System Surgical Procedure, Urologic Surgical Procedure, Prevention of venous thromboembolism, Abdominal surgery