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

Venous Thromboembolism Clinical Trial

— TREK  

Official 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00331838
• Other study ID #: DRI6243
• Secondary ID: 2005-006202-26
• Status: Completed
• Phase: Phase 2
• First received: May 18, 2006
• Last updated: January 14, 2013
• Start date: May 2006
• Est. completion date: June 2007

Study information

• Verified date: January 2013
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: Denmark: Danish Medicines AgencySpain: Spanish Agency of MedicinesPoland: Ministry of Health
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 705
• Est. completion date: June 2007
• Est. primary completion date: June 2007
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Thromboembolism
• Venous Thromboembolism

Intervention

Drug:
• Semuloparin sodium
0.8 mL solution in Type I amber glass vials Subcutaneous injection
• Placebo (for Enoxaparin sodium)
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
0.4 mL solution in ready-to-use pre-filled syringe Subcutaneous injection
• Placebo (for Semuloparin sodium)
0.8 ml solution in type I amber glass vials strictly identical in appearance containing the same volume but without active component Subcutaneous injection

Locations

Country	Name	City	State
Argentina	Sanofi-Aventis Administrative Office	Buenos Aires
Bulgaria	Sanofi-Aventis Administrative Office	Sofia
Chile	Sanofi-Aventis Administrative Office	Santiago
Colombia	Sanofi-Aventis Administrative Office	Santafe de Bogota
Denmark	Sanofi-Aventis Administrative Office	Horsholm
Finland	Sanofi-Aventis Administrative Office	Helsinki
Greece	Sanofi-Aventis Administrative Office	Athens
Malaysia	Sanofi-Aventis Administrative Office	Kuala Lumpur
Mexico	Sanofi-Aventis Administrative Office	Mexico
Norway	Sanofi-Aventis Administrative Office	Lysaker
Philippines	Sanofi-Aventis Administrative Office	Makati City
Poland	Sanofi-Aventis Administrative Office	Warszawa
Portugal	Sanofi-Aventis Administrative Office	Porto Salvo
Romania	Sanofi-Aventis Administrative Office	Bucuresti
Russian Federation	Sanofi-Aventis Administrative Office	Moscow
Sweden	Sanofi-Aventis Administrative Office	Bromma
Taiwan	Sanofi-Aventis Administrative Office	Taipei
Thailand	Sanofi-Aventis Administrative Office	Bangkok
Turkey	Sanofi-Aventis Administrative Office	Istanbul

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

Argentina,  Bulgaria,  Chile,  Colombia,  Denmark,  Finland,  Greece,  Malaysia,  Mexico,  Norway,  Philippines,  Poland,  Portugal,  Romania,  Russian Federation,  Sweden,  Taiwan,  Thailand,  Turkey, 

References & Publications (1)

Lassen MR, Dahl OE, Mismetti P, Destrée D, Turpie AG. AVE5026, a new hemisynthetic ultra-low-molecular-weight heparin for the prevention of venous thromboembolism in patients after total knee replacement surgery--TREK: a dose-ranging study. J Thromb Haemo — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Deaths	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).	From 1st study drug injection up to 3 days after last study drug injection (median duration of approximately 11 days)	Yes
Other	Platelets Count: Number of Participants With Potentially Clinically Significant Abnormalities [PCSA]	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.	From 1st study drug injection up to 3 days after last study drug injection (median duration of approximately 11 days)	Yes
Other	Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities [PCSA]	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.	From 1st study drug injection up to 3 days after last study drug injection (median duration of approximately 11 days)	Yes
Primary	Number of Participants Who Experienced Venous Thromboembolism Event (VTE) or VTE-related Death	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).	From surgery to Day 11 or the day of mandatory venography, whichever came first	No
Secondary	Number of Participants Who Experienced DVT		From surgery up to Day 11 or the day of mandatory venography, whichever came first	No
Secondary	Number of Participants Who Experienced Symptomatic VTE	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.	From surgery up to Day 11 or the day of mandatory venography, whichever came first	No
Secondary	Number of Participants Who Experienced Bleedings	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).	From 1st study drug injection up to 3 days after last study drug injection (median duration of approximately 11 days)	Yes
Secondary	Number of Participants Who Required 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 answers to questions asked after diagnostic tests for suspected VTE and/or the mandatory venography.	From surgery up to Day 11 or the day of mandatory venography, whichever came first	No