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

NCT ID: NCT00718224

Last Updated: 2013-01-23

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 1150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2008-07-31
• Study Completion Date: 2009-05-31

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.

Conditions

Venous Thromboembolism

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: PREVENTION
• Blinding Strategy: QUADRUPLE

Study Groups

Semuloparin

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

Group Type: EXPERIMENTAL

Semuloparin sodium

Intervention Type: DRUG

0.3 mL (0.2 mL if SRI) solution in ready-to-use 0.5 mL pre-filled syringe

Subcutaneous injection

Placebo

Intervention Type: DRUG

0.3 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

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

Group Type: ACTIVE_COMPARATOR

Enoxaparin

Intervention Type: DRUG

0.3 mL (0.2 mL if SRI) solution in ready-to-use 0.5 mL pre-filled syringe

Subcutaneous injection

Placebo

Intervention Type: DRUG

0.3 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

Interventions

Semuloparin sodium

0.3 mL (0.2 mL if SRI) solution in ready-to-use 0.5 mL pre-filled syringe

Subcutaneous injection

Intervention Type: DRUG

Enoxaparin

0.3 mL (0.2 mL if SRI) solution in ready-to-use 0.5 mL pre-filled syringe

Subcutaneous injection

Intervention Type: DRUG

Placebo

0.3 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

Intervention Type: DRUG

Other Intervention Names

AVE5026; Lovenox®

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Sanofi

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Michael R. LASSEN, MD

Role: PRINCIPAL_INVESTIGATOR

Horsholm Hospital, Horsholm, Denmark

Alexander G. TURPIE, MD

Role: STUDY_CHAIR

McMaster University

Locations

Sanofi-Aventis Administrative Office

Bridgewater, New Jersey, United States

Sanofi-Aventis Administrative Office

Buenos Aires, , Argentina

sanofi-aventis Australia & New Zealand administrative office

Macquarie Park, New South Wales, Australia

Sanofi-Aventis Administrative Office

Minsk, , Belarus

Sanofi-Aventis Administrative Office

Laval, , Canada

Sanofi-Aventis Administrative Office

Bogotá, , Colombia

Sanofi-Aventis Administrative Office

Prague, , Czechia

Sanofi-Aventis Administrative Office

Hørsholm, , Denmark

Sanofi-Aventis Administrative Office

Tallinn, , Estonia

Sanofi-Aventis Administrative Office

Athens, , Greece

Sanofi-Aventis Administrative Office

Vilnius, , Lithuania

Sanofi-Aventis Administrative Office

México, , Mexico

Sanofi-Aventis Administrative Office

Warsaw, , Poland

Sanofi-Aventis Administrative Office

Bucharest, , Romania

Sanofi-Aventis Administrative Office

Moscow, , Russia

Sanofi-Aventis Administrative Office

Midrand, , South Africa

Sanofi-Aventis Administrative Office

Kiev, , Ukraine

Countries

United States; Argentina; Australia; Belarus; Canada; Colombia; Czechia; Denmark; Estonia; Greece; Lithuania; Mexico; Poland; Romania; Russia; South Africa; Ukraine

References

Lassen MR, Fisher W, Mouret P, Agnelli G, George D, Kakkar A, Mismetti P, Turpie AG; SAVE Investigators. Semuloparin for prevention of venous thromboembolism after major orthopedic surgery: results from three randomized clinical trials, SAVE-HIP1, SAVE-HIP2 and SAVE-KNEE. J Thromb Haemost. 2012 May;10(5):822-32. doi: 10.1111/j.1538-7836.2012.04701.x.

Reference Type: RESULT

PMID: 22429800 (View on PubMed)

Other Identifiers

2007-007946-37

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

EFC10571

Identifier Type: -

Identifier Source: org_study_id