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Completed

NCT Number: NCT00331838

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

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.

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Key information

Conditions

Venous Thromboembolism Cardiovascular Diseases Embolism and Thrombosis Thromboembolism Thrombosis Vascular Diseases Venous Thrombosis

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 2

Primary location

Sanofi-Aventis Administrative Office, Buenos Aires, Argentina

Loading trial locations.

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

Semuloparin sodium

Drug

0.8 mL solution in Type I amber glass vials

Subcutaneous injection

Other names: AVE5026

Placebo (for Enoxaparin sodium)

Drug

0.4 mL solution in ready-to-use prefilled syringe strictly identical in appearance containing the same volume but without active component

Subcutaneous injection

Enoxaparin sodium

Drug

0.4 mL solution in ready-to-use pre-filled syringe

Subcutaneous injection

Other names: Lovenox®

Placebo (for Semuloparin sodium)

Drug

0.8 ml solution in type I amber glass vials strictly identical in appearance containing the same volume but without active component

Subcutaneous injection

Primary outcomes

  1. Number of Participants Who Experienced Venous Thromboembolism Event (VTE) or VTE-related Death

    Time frame: From surgery to Day 11 or the day of mandatory venography, whichever came first

    VTE included any Deep Vein Thrombosis [DVT] identified on mandatory venography of the lower limbs; symptomatic DVT and/or non-fatal pulmonary embolism [PE] before mandatory examination; VTE related deaths included fatal PE or deaths which could not be attributed to a documented cause and for which PE could not be ruled out. All events were to be confirmed by a Central Independent Adjudication Committee [CIAC] based on venographies, scheduled or unscheduled, and other available diagnostic tests (ultrasonography, ventilation/perfusion lung scan, pulmonary angiography, autopsy report, etc).

Secondary outcomes

  1. Number of Participants Who Experienced DVT

    Time frame: From surgery up to Day 11 or the day of mandatory venography, whichever came first

  2. Number of Participants Who Experienced Symptomatic VTE

    Time frame: From surgery up to Day 11 or the day of mandatory venography, whichever came first

    Symptomatic VTE included:

    • suspected DVT confirmed by the CIAC based on compression ultrasonography or venography;
    • suspected PE confirmed by the CIAC based on perfusion/ventilation lung scan, pulmonary angiography or spiral computerized tomography.

  3. Number of Participants Who Experienced Bleedings

    Time frame: From 1st study drug injection up to 3 days after last study drug injection (median duration of approximately 11 days)

    Bleedings were centrally and blindly reviewed by the CIAC and classified as:

    • "Major" (fatal bleeding, bleeding that was retroperitoneal or intracranial or that involved any other critical organ (e.g. eye, adrenal gland, pericardium or spine), surgical site bleeding leading to intervention, non-surgical site bleeding requiring surgical intervention or with a bleeding index ≥2);
    • "Minor" (overt bleeding considered more than expected but not meeting the criteria for major bleeding);
    • "Criteria for bleeding event not satisfied" (not meeting the criteria for major or minor bleeding).

  4. Number of Participants Who Required Initiation of Curative Anticoagulant or Thrombolytic Treatment After VTE Assessment

    Time frame: From surgery up to Day 11 or the day of mandatory venography, whichever came first

    Initiation of curative anticoagulant or thrombolytic treatment after VTE assessment was defined from investigator's answers to questions asked after diagnostic tests for suspected VTE and/or the mandatory venography.

Other outcomes

  1. Number of Deaths

    Time frame: From 1st study drug injection up to 3 days after last study drug injection (median duration of approximately 11 days)

    All deaths were centrally and blindly reviewed by the CIAC and classified as "Fatal PE", "PE not excluded", "Fatal bleeding" and "Death not associated with VTE or bleeding" based on relevant documentation (e.g. autopsy report).

  2. Platelets Count: Number of Participants With Potentially Clinically Significant Abnormalities [PCSA]

    Time frame: From 1st study drug injection up to 3 days after last study drug injection (median duration of approximately 11 days)

    PCSA are abnormal values considered medically important by the Sponsor according to predefined criteria based on literature review. Threshold for platelet counts was defined as <100 Giga/L.

  3. Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities [PCSA]

    Time frame: From 1st study drug injection up to 3 days after last study drug injection (median duration of approximately 11 days)

    Thresholds were defined as follows:

    • Alanine Aminotransferase [ALAT] >3 Upper Normal Limit [ULN];
    • Total Bilirubin [TB] ≥34 μmol/L;
    • ALAT ≥3 ULN and TB ≥34 μmol/L.

Sponsors and collaborators

Lead sponsor

Sanofi

Industry

Registry information

Official study title

A Multicenter, Randomized, Double-Blind, Double-Dummy, Parallel Group, Dose Response Study of Subcutaneous AVE5026 With an Enoxaparin Calibrator Arm in the Prevention of Venous Thromboembolism in Patients Undergoing Elective Total Knee Replacement Surgery

Acronym: TREK

Important dates

Study start
2006
Primary completion
2007
Study completion
2007
First posted
May 31, 2006
Registry last updated
Jan 15, 2013

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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