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Evaluation of AVE5026 as Compared to Enoxaparin for the Prevention of Thromboembolism in Patients Undergoing Total Hip Replacement Surgery

Phase 3
Completed
Conditions
Venous Thromboembolism
Interventions
Registration Number
NCT00697099
Lead Sponsor
Sanofi
Brief Summary

The primary objective was to compare the efficacy of once daily \[q.d.\] subcutaneous \[s.c.\] injections of Semuloparin sodium (AVE5026) with q.d. s.c. injections of enoxaparin for the prevention of Venous Thromboembolic Events \[VTE\] in patients undergoing elective total hip replacement surgery.

The secondary objectives were to evaluate the safety of AVE5026 in patients undergoing elective total hip replacement surgery, and to document AVE5026 exposure in this population.

Detailed Description

Randomization had to take place just prior the first study drug injection (randomization ratio 1:1).

The total duration of observation per participant was 35-42 days from surgery broken down as follows:

* 7 to 10-day double-blind treatment period;

* 28 to 35-day follow-up period.

Mandatory bilateral venography of the lower limbs had to be performed 7 to 11 days after surgery.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
2326
Inclusion Criteria
  • Elective total hip replacement surgery or a revision of at least one component of a prosthesis implanted ≥ 6 months prior to study entry.
Exclusion Criteria
  • Any major orthopedic surgery in the 3 months prior to study start;
  • Deep vein thrombosis or pulmonary embolism within the last 12 months or known post-phlebitic syndrome;
  • High risk of bleeding;
  • Known allergy to heparin or enoxaparin;
  • Any contra-indications to the performance of venography;
  • End stage renal disease or patient on dialysis.

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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
SemuloparinSemuloparin sodiumSemuloparin sodium 20 mg (10 mg if Severe Renal Impairment \[SRI\]) once daily for 7-10 days with an initial dose given 8 hours after surgery Placebo for Enoxaparin sodium prior to surgery according to local standard for Enoxaparin and 12 hours after surgery to maintain the blind
SemuloparinPlaceboSemuloparin sodium 20 mg (10 mg if Severe Renal Impairment \[SRI\]) once daily for 7-10 days with an initial dose given 8 hours after surgery Placebo for Enoxaparin sodium prior to surgery according to local standard for Enoxaparin and 12 hours after surgery to maintain the blind
EnoxaparinEnoxaparin sodiumEnoxaparin sodium 40 mg (20 mg if Severe Renal Impairment \[SRI\]) once daily for 7-10 days with an initial dose given prior to or 12 hours after surgery according to local standard for Enoxaparin sodium Placebo for Semuloparin sodium 8 hours after surgery to maintain the blind
EnoxaparinPlaceboEnoxaparin sodium 40 mg (20 mg if Severe Renal Impairment \[SRI\]) once daily for 7-10 days with an initial dose given prior to or 12 hours after surgery according to local standard for Enoxaparin sodium Placebo for Semuloparin sodium 8 hours after surgery to maintain the blind
Primary Outcome Measures
NameTimeMethod
Percentage of Participants Who Experienced Venous Thromboembolism Event [VTE] or Death From Any CauseFrom randomization up to 10 days after surgery or the day of mandatory venography, whichever came first

VTE included any proximal or distal Deep Vein Thrombosis \[DVT\] (symptomatic or not) and non-fatal Pulmonary Embolism \[PE\] as confirmed by a Central Independent Adjudication Committee \[CIAC\] after review of mandatory bilateral venograms and diagnostic tests for VTE.

All-cause deaths included fatal PE and deaths for other reason than PE.

Secondary Outcome Measures
NameTimeMethod
Percentage of Participants Who Experienced "Major" VTE or All-cause DeathFrom randomization up to 10 days after surgery or the day of mandatory venography, whichever came first

"major" VTE included any proximal DVT, symptomatic distal DVT and nonfatal Pulmonary Embolism (PE) as confirmed by the CIAC.

Percentage of Participants Who Experienced Clinically Relevant BleedingsFrom first study drug injection up to 3 days after last study drug injection

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

* "major" (fatal, in a critical area/organ, causing a post-operative drop in hemoglobin ≥2 g/dL or requiring post-operative transfusion ≥2 units of blood, leading to an invasive diagnostic or therapeutic intervention, or associated with circulatory decompensation);

* "clinically relevant non-major" (skin hematoma or epistaxis requiring surgical/medical intervention/treatment, macroscopic hematuria, or overt bleeding requiring specific attention by healthcare professional);

* "Non-clinically relevant bleeding".

Percentage of Participants Who Required the Initiation of Curative Anticoagulant or Thrombolytic Treatment After VTE AssessmentFrom randomization up to 10 days after surgery or the day of mandatory venography, whichever came first

Initiation of curative anticoagulant or thrombolytic treatment after VTE assessment was defined from investigator's answer to the question "was the subject treated for VTE?" asked after the diagnostic tests for suspected VTE and after the mandatory venography.

Trial Locations

Locations (3)

sanofi-aventis Australia & New Zealand administrative office

🇦🇺

Macquarie Park, New South Wales, Australia

Sanofi-Aventis Administraive Office

🇨🇳

Taipei, Taiwan

Sanofi-Aventis Administrative Office

🇺🇦

Kiev, Ukraine

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