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
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Sponsor
- Sanofi
- Enrollment
- 705
- Locations
- 1
- Primary Endpoint
- Number of Participants Who Experienced Venous Thromboembolism Event (VTE) or VTE-related Death
Study Overview
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.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
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.
Arms & Interventions
Semuloparin 5 mg
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
Intervention: Semuloparin sodium (Drug)
Enoxaparin 40 mg
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
Intervention: Enoxaparin sodium (Drug)
Semuloparin 5 mg
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
Intervention: Placebo (for Enoxaparin sodium) (Drug)
Semuloparin 10 mg
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
Intervention: Semuloparin sodium (Drug)
Semuloparin 10 mg
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
Intervention: Placebo (for Enoxaparin sodium) (Drug)
Semuloparin 20 mg
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
Intervention: Semuloparin sodium (Drug)
Semuloparin 20 mg
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
Intervention: Placebo (for Enoxaparin sodium) (Drug)
Semuloparin 40 mg
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
Intervention: Semuloparin sodium (Drug)
Semuloparin 40 mg
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
Intervention: Placebo (for Enoxaparin sodium) (Drug)
Semuloparin 60 mg
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
Intervention: Semuloparin sodium (Drug)
Semuloparin 60 mg
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
Intervention: Placebo (for Enoxaparin sodium) (Drug)
Enoxaparin 40 mg
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
Intervention: Placebo (for Semuloparin sodium) (Drug)
Placebo pre-op / Semuloparin 20 mg
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
Intervention: Semuloparin sodium (Drug)
Placebo pre-op / Semuloparin 20 mg
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
Intervention: Placebo (for Enoxaparin sodium) (Drug)
Placebo pre-op / Semuloparin 20 mg
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
Intervention: Placebo (for Semuloparin sodium) (Drug)
Placebo pre-op / Semuloparin 40 mg
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
Intervention: Semuloparin sodium (Drug)
Placebo pre-op / Semuloparin 40 mg
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
Intervention: Placebo (for Enoxaparin sodium) (Drug)
Placebo pre-op / Semuloparin 40 mg
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
Intervention: Placebo (for Semuloparin sodium) (Drug)
Outcomes
Primary Outcomes
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
- Number of Participants Who Experienced DVT(From surgery up to Day 11 or the day of mandatory venography, whichever came first)
- Number of Participants Who Experienced Symptomatic VTE(From surgery up to Day 11 or the day of mandatory venography, whichever came first)
- Number of Participants Who Experienced Bleedings(From 1st study drug injection up to 3 days after last study drug injection (median duration of approximately 11 days))
- Number of Participants Who Required Initiation of Curative Anticoagulant or Thrombolytic Treatment After VTE Assessment(From surgery up to Day 11 or the day of mandatory venography, whichever came first)