Evaluation of AVE5026 as Compared to Enoxaparin for the Prevention of Thromboembolism in Patients Undergoing Elective Knee Replacement Surgery

Phase 3

Completed

• Conditions: Venous Thromboembolism
• Interventions: Drug: Semuloparin sodium; Drug: Enoxaparin; Drug: Placebo

• Registration Number: NCT00718224
• Lead Sponsor: Sanofi

Brief Summary

The primary objective was to compare the efficacy of Semuloparin sodium (AVE5026) with Enoxaparin for the prevention of Venous Thromboembolic Events \[VTE\] in patients undergoing elective knee replacement surgery.

The secondary objectives were to evaluate the safety of AVE5026 in patients undergoing elective knee replacement surgery, and to document AVE5026 exposure in this population.

Detailed Description

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

Study Timeline

• Study Start: 2008-07
• Study First Submitted: 2008-07-17
• Study First Submitted QC: 2008-07-17
• Study First Posted: 2008-07-18
• Primary Completion: 2009-05
• Study Completion: 2009-05
• Disposition First Submitted: 2010-12-20
• Disposition First Submitted QC: 2010-12-20
• Disposition First Posted: 2010-12-28
• Status Verified: 2013-01
• Last Update Submitted: 2013-01-14
• Last Update Posted: 2013-01-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 1150

Inclusion Criteria

• Knee replacement surgery or revision of at least one component of a knee prosthesis implanted ≥ 6 months prior to study entry.

Exclusion Criteria

• Any major orthopedic surgeries in the 3 months prior to study;
• Deep vein thrombosis or pulmonary embolism within the last 12 months, or known post-phlebitic syndrome;
• Any contraindications to the performance of venography;
• High risk of bleeding;
• Know 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Semuloparin	Semuloparin sodium	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 To maintain the blind, placebo for Enoxaparin sodium: * 12 and 24 hours after surgery, then once daily if no SRI * 12 hours after surgery only if SRI
Semuloparin	Placebo	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 To maintain the blind, placebo for Enoxaparin sodium: * 12 and 24 hours after surgery, then once daily if no SRI * 12 hours after surgery only if SRI
Enoxaparin	Enoxaparin	Enoxaparin sodium 30 mg twice daily (20 mg once daily if Severe Renal Impairment \[SRI\]) for 7-10 days with an initial dose given 12 hours after surgery Placebo for Semuloparin sodium 8 hours after surgery to maintain the blind
Enoxaparin	Placebo	Enoxaparin sodium 30 mg twice daily (20 mg once daily if Severe Renal Impairment \[SRI\]) for 7-10 days with an initial dose given 12 hours after surgery Placebo for Semuloparin sodium 8 hours after surgery to maintain the blind

Primary Outcome Measures

Name	Time	Method
Percentage of Participants Who Experienced Venous Thromboembolism Event (VTE) or All-cause Death	From randomization up to 10 days after surgery or the day of mandatory venography, whichever came first	VTE included 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 central and blind review of mandatory bilateral venograms and diagnostic tests for VTE.; All-cause deaths included fatal PE and deaths for other reason than PE.

Secondary Outcome Measures

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

Trial Locations

Locations (2)

Sanofi-Aventis Administrative Office; 🇺🇦 Kiev, Ukraine

sanofi-aventis Australia & New Zealand administrative office; 🇦🇺 Macquarie Park, New South Wales, Australia