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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00697099
First received: June 12, 2008
Last updated: January 14, 2013
Last verified: January 2013
  Purpose

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.


Condition Intervention Phase
Venous Thromboembolism
Drug: Semuloparin sodium
Drug: Enoxaparin sodium
Drug: Placebo
Phase 3

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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

    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:
  • 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 ] [ Designated as safety issue: No ]
    "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 Bleedings [ Time Frame: From first study drug injection up to 3 days after last study drug injection ] [ Designated as safety issue: Yes ]

    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 Assessment [ Time Frame: From randomization up to 10 days after surgery or the day of mandatory venography, whichever came first ] [ Designated as safety issue: No ]
    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.


Other Outcome Measures:
  • Overview of deaths [ Time Frame: From first study drug injection up to 3 days after last study drug injection ] [ Designated as safety issue: Yes ]
    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).

  • 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 ] [ Designated as safety issue: Yes ]

    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.


  • 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 ] [ Designated as safety issue: Yes ]

    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.



Enrollment: 2326
Study Start Date: June 2008
Study Completion Date: June 2009
Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 Name: 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 Name: 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


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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00697099

  Hide Study Locations
Locations
United States, New Jersey
Sanofi-Aventis Administrative Office
Bridgewater, New Jersey, United States, 08807
Argentina
Sanofi-Aventis Administrative Office
Buenos Aires, Argentina
Australia, New South Wales
sanofi-aventis Australia & New Zealand administrative office
Macquarie Park, New South Wales, Australia
Belarus
Sanofi-Aventis Administrative Office
Minsk, Belarus
Canada
Sanofi-Aventis Administrative Office
Laval, Canada
Chile
Sanofi-Aventis Administrative Office
Santiago, Chile
Colombia
Sanofi-Aventis Administrative Office
Santafe de Bogota, Colombia
Czech Republic
Sanofi-Aventis Administrative Office
Praha, Czech Republic
Denmark
Sanofi-Aventis Administrative Office
Horsholm, Denmark
Estonia
Sanofi-Aventis Administrative Office
Tallinn, Estonia
Finland
Sanofi-Aventis Administrative Office
Helsinki, Finland
Germany
Sanofi-Aventis Administrative Office
Berlin, Germany
Greece
Sanofi-Aventis Administrative Office
Athens, Greece
India
Sanofi-Aventis Administrative Office
Mumbai, India
Italy
Sanofi-Aventis Administrative Office
Milano, Italy
Mexico
Sanofi-Aventis Administrative Office
Mexico, Mexico
Norway
Sanofi-Aventis Administrative Office
Lysaker, Norway
Peru
Sanofi-Aventis Administrative Office
Lima, Peru
Philippines
Sanofi-Aventis Administrative Office
Makati City, Philippines
Poland
Sanofi-Aventis Administrative Office
Warszawa, Poland
Romania
Sanofi-Aventis Administrative Office
Bucuresti, Romania
Russian Federation
Sanofi-Aventis Administrative Office
Moscow, Russian Federation
Slovakia
Sanofi-Aventis Administrative Office
Brastislava, Slovakia
South Africa
Sanofi-Aventis Administrative Office
Midrand, South Africa
Spain
Sanofi-Aventis Administrative Office
Barcelona, Spain
Sweden
Sanofi-Aventis Administrative Office
Bromma, Sweden
Taiwan
Sanofi-Aventis Administraive Office
Taipei, Taiwan
Thailand
Sanofi-Aventis Administrative Office
Bangkok, Thailand
Turkey
Sanofi-Aventis Administrative Office
Istanbul, Turkey
Ukraine
Sanofi-Aventis Administrative Office
Kiev, Ukraine
Sponsors and Collaborators
Sanofi
Investigators
Principal Investigator: Patrick MOURET, MD Orthopädische Klinik, Stätische Klinik, Gotenstrasse 6-8, Frankfurt Höechst, 65929 Frankfurt, Germany
Study Chair: Alexander G. TURPIE, MD HHS-General Hospital, Hamilton, Ontario, Canada
  More Information

Publications:
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00697099     History of Changes
Other Study ID Numbers: EFC10342, 2007-007944-80
Study First Received: June 12, 2008
Last Updated: January 14, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanofi:
VTE prevention
Total Hip Replacement
Heparin Low-Molecular-Weight

Additional relevant MeSH terms:
Thromboembolism
Venous Thromboembolism
Venous Thrombosis
Cardiovascular Diseases
Embolism and Thrombosis
Thrombosis
Vascular Diseases
Enoxaparin
Anticoagulants
Cardiovascular Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on November 19, 2014