Evaluation of AVE5026 in the Prevention of Venous Thromboembolism in Acutely Ill Medical Patients With Restricted Mobility

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 primary prevention of Venous Thromboembolic Events [VTE] in patients hospitalized for acute medical illness. The secondary objectives were to evaluate the safety of AVE5026 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. The total duration of observation per participant was 35-42 days from randomization broken down as follows: 10 to 14-day double-blind treatment period; 25 to 32-day follow-up period. Mandatory bilateral compression ultrasound [CUS] had to be performed between 10 to 15 days after randomization.

Official Title
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A Multinational, Multicenter, Randomized, Double-Blind Study Comparing the Efficacy and Safety of AVE5026 With Enoxaparin for the Primary Prevention of Venous Thromboembolism in Acutely Ill Medical Patients With Restricted Mobility

Conditions
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Venous Thromboembolism

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


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patient with an acute medical condition requiring bed rest for at least 3 days, and hospitalized for at least one of the following medical conditions: Congestive heart failure (New York Heart Association [NYHA] class III/IV); Acute respiratory failure (not requiring mechanical ventilation); Acute infection (without septic shock)*; Acute rheumatic disorder*; Acute episode of inflammatory bowel disease*. Patient with one of these conditions should have at least one additional risk factor for venous thromboembolism (VTE) among the following: Age ≥ 75 years; Active cancer or myeloproliferative disorders (having received treatment for cancer within the last 6 months); Previous VTE; Obesity; Oral hormone therapy (antiandrogen or estrogen); Chronic heart failure; Chronic respiratory failure. Exclusion Criteria: Previous surgery with general anesthesia within 30 days before inclusion in the study; Patient requiring a curative anticoagulant or thrombolytic treatment; Patient at risk of bleeding; Stroke; Known hypersensitivity to heparin or enoxaparin sodium; 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: 40 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 10-14 days | 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;|
| Active Comparator: Enoxaparin<br>Enoxaparin sodium 40 mg (20 mg if Severe Renal Impairment [SRI]) once daily for 10-14 days | 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®;|

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 VTE-related Death | VTE included: asymptomatic proximal Deep Vein Thrombosis (DVT) detected by the mandatory CUS and confirmed by a Compression Ultrasound Adjudication Committee (CUSAC) after central and blind review of the mandatory CUS; symptomatic DVT and non-fatal Pulmonary Embolism (PE) reported by the investigator and confirmed by a Central Independent Adjudication Committee (CIAC) after central and blind review of diagnosis tests. VTE-related Death included fatal PE and unexplained deaths. | From randomization up to 15 days after randomization or the day of the mandatory Compression Ultrasound (CUS), whichever came first | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants Who Experienced asymptomatic proximal DVT |  | From randomization up to 15 days after randomization or the day of the mandatory CUS, 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, symptomatic in a critical area/organ, causing a post-operative drop in hemoglobin ≥2 g/dL or requiring post-operative transfusion ≥2 units of blood); clinically relevant non-major (overt bleeding requiring medical intervention and not meeting criteria for major bleeding); Non-clinically relevant bleeding. | From 1st 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 CUS. | From randomization up to 15 days after randomization or the day of mandatory CUS, whichever came first | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Venous thrombosis, Primary prevention