Prevention of Venous Thromboembolism in Patients Undergoing Elective Total Knee Replacement Surgery (TREK)

Sanofi

Status and phase: Completed; Phase 2

Conditions: Venous Thromboembolism

Treatments: Drug: Semuloparin sodium; Drug: Enoxaparin sodium; Drug: Placebo (for Semuloparin sodium); Drug: Placebo (for Enoxaparin sodium)

Study type: Interventional

Funder types: Industry

Identifiers

NCT00331838

DRI6243

2005-006202-26 (EudraCT Number)

Details and patient eligibility

About

The primary objective was to demonstrate the dose-response of Semuloparin sodium (AVE5026) for the prevention of Venous Thromboembolism [VTE] in patients undergoing total knee replacement [TKR] surgery.

Secondary objectives were to evaluate the safety (incidence of major bleeding) of AVE5026, to document the efficacy and safety of AVE5026 post-operative regimens, and to assess the pharmacokinetic parameters of AVE5026.

Full description

The randomization had to take place before the first study drug injection.

The total duration of observation per participant was 27-33 days from surgery broken down as follows:

• 4 to 10-day double-blind treatment period;
• Follow-up period up to Day 30 ± 3 after surgery.

Mandatory bilateral venography of the lower limbs had to be performed between 5 to 11 days after surgery.

Enrollment: 705 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Patient scheduled to undergo elective total knee replacement or revision of a primary procedure performed ≥ 6 months prior to study entry.

Exclusion criteria

• Any major orthopedic surgery in the 3 months prior to study entry;
• Clinical signs or symptoms of DVT or PE within the last 12 months or known post-phlebitic syndrome;
• Known sensitivity to iodine or contrast dyes;
• Recent stroke or myocardial infarction;
• High risk of bleeding;
• Treatment with other anti-thrombotic agents within 7 days prior to surgery;
• Any contra-indication to Unfractionated Heparin or Low Molecular Weight Heparin;
• Pregnant or nursing woman, or woman of childbearing potential who is not using an effective contraceptive method.

The above information is not intended to contain all considerations relevant to a patient's potential participation in a clinical trial.

Trial design

Primary purpose: Prevention

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Triple Blind

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705 participants in 8 patient groups

Semuloparin 5 mg

Experimental group

Description:

Semuloparin sodium 5 mg + Placebo (for Enoxaparin sodium) once daily for 4-10 days with an initial dose given 12 hours before or 8 hours after surgery depending on the willingness of the investigator

Treatment:

Drug: Placebo (for Enoxaparin sodium)

Drug: Semuloparin sodium

Semuloparin 10 mg

Experimental group

Description:

Semuloparin sodium 10 mg + Placebo (for Enoxaparin sodium) once daily for 4-10 days with an initial dose given 12 hours before or 8 hours after surgery depending on the willingness of the investigator

Treatment:

Drug: Placebo (for Enoxaparin sodium)

Drug: Semuloparin sodium

Semuloparin 20 mg

Experimental group

Description:

Semuloparin sodium 20 mg + Placebo (for Enoxaparin sodium) once daily for 4-10 days with an initial dose given 12 hours before or 8 hours after surgery depending on the willingness of the investigator

Treatment:

Drug: Placebo (for Enoxaparin sodium)

Drug: Semuloparin sodium

Semuloparin 40 mg

Experimental group

Description:

Semuloparin sodium 40 mg + Placebo (for Enoxaparin sodium) once daily for 4-10 days with an initial dose given 12 hours before or 8 hours after surgery depending on the willingness of the investigator

Treatment:

Drug: Placebo (for Enoxaparin sodium)

Drug: Semuloparin sodium

Semuloparin 60 mg

Experimental group

Description:

Semuloparin sodium 60 mg + Placebo (for Enoxaparin sodium) once daily for 4-10 days with an initial dose given 12 hours before or 8 hours after surgery depending on the willingness of the investigator

Treatment:

Drug: Placebo (for Enoxaparin sodium)

Drug: Semuloparin sodium

Enoxaparin 40 mg

Active Comparator group

Description:

Enoxaparin sodium 40 mg + Placebo (for Semuloparin sodium) once daily for 4-10 days with an initial dose given 12 hours before or 8 hours after surgery depending on the willingness of the investigator

Treatment:

Drug: Enoxaparin sodium

Drug: Placebo (for Semuloparin sodium)

Placebo pre-op / Semuloparin 20 mg

Experimental group

Description:

Placebo (for Semuloparin sodium) + Placebo (for Enoxaparin sodium) 12 hours before surgery then, Semuloparin sodium 20 mg + Placebo (for Enoxaparin sodium) once daily for 4-10 days with an initial dose given 8 hours after surgery

Treatment:

Drug: Placebo (for Enoxaparin sodium)

Drug: Semuloparin sodium

Drug: Placebo (for Semuloparin sodium)

Placebo pre-op / Semuloparin 40 mg

Experimental group

Description:

Placebo (for Semuloparin sodium) + Placebo (for Enoxaparin sodium) 12 hours before surgery then, Semuloparin sodium 40 mg + Placebo (for Enoxaparin sodium) once daily for 4-10 days with an initial dose given 8 hours after surgery

Treatment:

Drug: Placebo (for Enoxaparin sodium)

Drug: Semuloparin sodium

Drug: Placebo (for Semuloparin sodium)