Evaluation of AVE5026 as Compared to Enoxaparin for the Prevention of Thromboembolism in Patients Undergoing Total Hip Replacement Surgery (SAVE-HIP1)

January 14, 2013 updated by: Sanofi

A Multinational, Multicenter, Randomized, Double-Blind Study Comparing the Efficacy and Safety of AVE5026 With Enoxaparin for the Prevention of Venous Thromboembolism in Patients Undergoing Elective Total Hip Replacement Surgery

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

2326

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Argentina
      • Buenos Aires, Argentina
        • Sanofi-Aventis Administrative Office
  • Australia
    • New South Wales
      • Macquarie Park, New South Wales, Australia
        • sanofi-aventis Australia & New Zealand administrative office
  • Belarus
      • Minsk, Belarus
        • Sanofi-Aventis Administrative Office
  • Canada
      • Laval, Canada
        • Sanofi-Aventis Administrative Office
  • Chile
      • Santiago, Chile
        • Sanofi-Aventis Administrative Office
  • Colombia
      • Santafe de Bogota, Colombia
        • Sanofi-Aventis Administrative Office
  • Czech Republic
      • Praha, Czech Republic
        • Sanofi-Aventis Administrative Office
  • Denmark
      • Horsholm, Denmark
        • Sanofi-Aventis Administrative Office
  • Estonia
      • Tallinn, Estonia
        • Sanofi-Aventis Administrative Office
  • Finland
      • Helsinki, Finland
        • Sanofi-Aventis Administrative Office
  • Germany
      • Berlin, Germany
        • Sanofi-Aventis Administrative Office
  • Greece
      • Athens, Greece
        • Sanofi-Aventis Administrative Office
  • India
      • Mumbai, India
        • Sanofi-Aventis Administrative Office
  • Italy
      • Milano, Italy
        • Sanofi-Aventis Administrative Office
  • Mexico
      • Mexico, Mexico
        • Sanofi-Aventis Administrative Office
  • Norway
      • Lysaker, Norway
        • Sanofi-Aventis Administrative Office
  • Peru
      • Lima, Peru
        • Sanofi-Aventis Administrative Office
  • Philippines
      • Makati City, Philippines
        • Sanofi-Aventis Administrative Office
  • Poland
      • Warszawa, Poland
        • Sanofi-Aventis Administrative Office
  • Romania
      • Bucuresti, Romania
        • Sanofi-Aventis Administrative Office
  • Russian Federation
      • Moscow, Russian Federation
        • Sanofi-Aventis Administrative Office
  • Slovakia
      • Brastislava, Slovakia
        • Sanofi-Aventis Administrative Office
  • South Africa
      • Midrand, South Africa
        • Sanofi-Aventis Administrative Office
  • Spain
      • Barcelona, Spain
        • Sanofi-Aventis Administrative Office
  • Sweden
      • Bromma, Sweden
        • Sanofi-Aventis Administrative Office
  • Taiwan
      • Taipei, Taiwan
        • Sanofi-Aventis Administraive Office
  • Thailand
      • Bangkok, Thailand
        • Sanofi-Aventis Administrative Office
  • Turkey
      • Istanbul, Turkey
        • Sanofi-Aventis Administrative Office
  • Ukraine
      • Kiev, Ukraine
        • Sanofi-Aventis Administrative Office
  • United States
    • New Jersey
      • Bridgewater, New Jersey, United States, 08807
        • Sanofi-Aventis Administrative Office

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Semuloparin

Semuloparin 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
Drug: Semuloparin sodium

0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe

Subcutaneous injection

Other Names:
  • AVE5026
Drug: Placebo

0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe strictly identical in appearance but without active component

Subcutaneous injection
Active Comparator: Enoxaparin

Enoxaparin 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
Drug: Enoxaparin sodium

0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe

Subcutaneous injection

Other Names:
  • Lovenox®
Drug: Placebo

0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe strictly identical in appearance but without active component

Subcutaneous injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Experienced Venous Thromboembolism Event [VTE] or Death From Any Cause
Time Frame: From 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.
From randomization up to 10 days after surgery or the day of mandatory venography, whichever came first

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Percentage of Participants Who Experienced Clinically Relevant Bleedings
Time Frame: From 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".
From first study drug injection up to 3 days after last study drug injection
Percentage of Participants Who Required the Initiation of Curative Anticoagulant or Thrombolytic Treatment After VTE Assessment
Time Frame: From 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.
From randomization up to 10 days after surgery or the day of mandatory venography, whichever came first
Percentage of Participants Who Experienced "Major" VTE or All-cause Death
Time Frame: From 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.
From randomization up to 10 days after surgery or the day of mandatory venography, whichever came first

Other Outcome Measures

Outcome Measure
Measure Description
Time Frame
Overview of deaths
Time Frame: From first study drug injection up to 3 days after last study drug injection
All deaths were centrally and blindly reviewed by the CIAC and classified as fatal PE, fatal bleeding, cardiovascular death or other based on relevant documentation (e.g. autopsy report).
From first study drug injection up to 3 days after last study drug injection
Liver Function: Percentage of Participants With Potentially Clinically Significant Abnormalities [PCSA]
Time Frame: From first study drug injection up to 3 days after last study drug injection

Thresholds were defined as follows:

  • Alanine Aminotransferase [ALAT] >3 Upper Normal Limit [ULN];
  • Total Bilirubin [TB] >2 ULN;
  • ALAT >3 ULN and TB >2 ULN;

Cases with ALAT >3 ULN and TB >2 ULN (not necessarily concomitant) were evaluated by a blinded independent adjudicator to determine if they met Hy's law criteria.
From first study drug injection up to 3 days after last study drug injection
Platelets Count: Percentage of Participants With Potentially Clinically Significant Abnormalities [PCSA]
Time Frame: From first study drug injection up to 3 days after last study drug injection

PCSA values 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 first study drug injection up to 3 days after last study drug injection

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sanofi

Investigators

  • Study Chair: Alexander G. TURPIE, MD, HHS-General Hospital, Hamilton, Ontario, Canada
  • Principal Investigator: Patrick MOURET, MD, Orthopädische Klinik, Stätische Klinik, Gotenstrasse 6-8, Frankfurt Höechst, 65929 Frankfurt, Germany

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

June 1, 2008

Primary Completion (Actual)

June 1, 2009

Study Completion (Actual)

June 1, 2009

Study Registration Dates

First Submitted

June 12, 2008

First Submitted That Met QC Criteria

June 12, 2008

First Posted (Estimate)

June 13, 2008

Study Record Updates

Last Update Posted (Estimate)

January 23, 2013

Last Update Submitted That Met QC Criteria

January 14, 2013

Last Verified

January 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • EFC10342
  • 2007-007944-80 (EudraCT Number)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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