Clinical trial NCT00331838: Prevention of Venous Thromboembolism in Patients Undergoing Elective Total Knee Replacement Surgery
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Venous Thromboembolism
Keywords: Prevention
Venous Thrombosis
Orthopedic Surgery
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2006-05-31
Enrollment: 705
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Number of Participants Who Experienced Venous Thromboembolism Event (VTE) or VTE-related Death
timeFrame: From surgery to Day 11 or the day of mandatory venography, whichever came first
Secondary outcomes:
measure: Number of Participants Who Experienced DVT
timeFrame: From surgery up to Day 11 or the day of mandatory venography, whichever came first
measure: Number of Participants Who Experienced Symptomatic VTE
timeFrame: From surgery up to Day 11 or the day of mandatory venography, whichever came first
measure: Number of Participants Who Experienced Bleedings
timeFrame: From 1st study drug injection up to 3 days after last study drug injection (median duration of approximately 11 days)
measure: Number of Participants Who Required Initiation of Curative Anticoagulant or Thrombolytic Treatment After VTE Assessment
timeFrame: From surgery up to Day 11 or the day of mandatory venography, whichever came first
Other outcomes:
measure: Number of Deaths
timeFrame: From 1st study drug injection up to 3 days after last study drug injection (median duration of approximately 11 days)
measure: Platelets Count: Number of Participants With Potentially Clinically Significant Abnormalities [PCSA]
timeFrame: From 1st study drug injection up to 3 days after last study drug injection (median duration of approximately 11 days)
measure: Liver Function: Number of Participants With Potentially Clinically Significant Abnormalities [PCSA]
timeFrame: From 1st study drug injection up to 3 days after last study drug injection (median duration of approximately 11 days)
Locations:
city: Buenos Aires
country: Argentina
facility: Sanofi-Aventis Administrative Office
city: Sofia
country: Bulgaria
facility: Sanofi-Aventis Administrative Office
city: Santiago
country: Chile
facility: Sanofi-Aventis Administrative Office
city: Santafe de Bogota
country: Colombia
facility: Sanofi-Aventis Administrative Office
city: Horsholm
country: Denmark
facility: Sanofi-Aventis Administrative Office
city: Helsinki
country: Finland
facility: Sanofi-Aventis Administrative Office
city: Athens
country: Greece
facility: Sanofi-Aventis Administrative Office
city: Kuala Lumpur
country: Malaysia
facility: Sanofi-Aventis Administrative Office
city: Mexico
country: Mexico
facility: Sanofi-Aventis Administrative Office
city: Lysaker
country: Norway
facility: Sanofi-Aventis Administrative Office
city: Makati City
country: Philippines
facility: Sanofi-Aventis Administrative Office
city: Warszawa
country: Poland
facility: Sanofi-Aventis Administrative Office
city: Porto Salvo
country: Portugal
facility: Sanofi-Aventis Administrative Office
city: Bucuresti
country: Romania
facility: Sanofi-Aventis Administrative Office
city: Moscow
country: Russian Federation
facility: Sanofi-Aventis Administrative Office
city: Bromma
country: Sweden
facility: Sanofi-Aventis Administrative Office
city: Taipei
country: Taiwan
facility: Sanofi-Aventis Administrative Office
city: Bangkok
country: Thailand
facility: Sanofi-Aventis Administrative Office
city: Istanbul
country: Turkey
facility: Sanofi-Aventis Administrative Office
Study officials:
affiliation: Hoersholm Hospital (Denmark)
name: Michael LASSEN, MD
role: STUDY_CHAIR
References:
citation: Lassen MR, Dahl OE, Mismetti P, Destree 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 Haemost. 2009 Apr;7(4):566-72. doi: 10.1111/j.1538-7836.2009.03301.x. Epub 2009 Jan 24.