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Evaluation of AVE5026 as Compared to Placebo for the Extended Prophylaxis of Venous Thromboembolism in Patients Having Undergone Hip Fracture Surgery (SAVE-HIP3)

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ClinicalTrials.gov Identifier: NCT00709904
Recruitment Status : Completed
First Posted : July 3, 2008
Last Update Posted : June 14, 2013
Sponsor:
Information provided by (Responsible Party):
Sanofi

Brief Summary:

The primary objective is to evaluate the efficacy of once daily (QD) subcutaneous (SC) injections of Semuloparin sodium (AVE5026) versus placebo for 3 additional weeks following an initial 7 to 10-day venous thromboprophylaxis with open-label AVE5026 in patients having undergone hip fracture surgery.

The secondary objective is to evaluate the safety of extended AVE5026 administration.


Condition or disease Intervention/treatment Phase
Venous Thromboembolism Drug: Open-label Semuloparin sodium Drug: Placebo (for Semuloparin sodium) Drug: Semuloparin sodium Phase 3

Detailed Description:

The total duration of observation per participant is 56-63 days from surgery broken down as follows:

  • 7 to 10-day initial treatment period with open-label Semuloparin sodium;
  • Randomization;
  • 19 to 23-day double-blind treatment period with Semuloparin sodium or placebo;
  • 30-day follow-up period.

Mandatory bilateral venography of the lower limbs is to be performed between 19 and 24 days after randomization.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 469 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Official Title: A Multinational, Multicenter, Randomized, Double-Blind Study Comparing the Efficacy and Safety of AVE5026 With Placebo for the Extended Prevention of Venous Thromboembolism in Patients Having Undergone Hip Fracture Surgery
Study Start Date : June 2008
Actual Primary Completion Date : January 2010
Actual Study Completion Date : January 2010

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: Semuloparin extension treatment
Extension treatment with Semuloparin sodium 20 mg (10 mg if SRI) for 19-23 days following initial treatment with open-label Semuloparin 20 mg (10 mg if SRI) for 7-10 days.
Drug: Open-label Semuloparin sodium

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

Subcutaneous injection once daily with an initial dose given 8 hours after surgery

Other Name: AVE5026

Drug: Semuloparin sodium

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

Subcutaneous injection once daily

Other Name: AVE5026

Placebo Comparator: Placebo extension treatment
Extension treatment with placebo (for Semuloparin sodium) for 19-23 days following initial treatment with open-label Semuloparin 20 mg (10 mg if SRI) for 7-10 days
Drug: Open-label Semuloparin sodium

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

Subcutaneous injection once daily with an initial dose given 8 hours after surgery

Other Name: AVE5026

Drug: Placebo (for Semuloparin sodium)

0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml prefilled syringe strictly identical in appearance containing the same volume but without active component

Subcutaneous injection once daily





Primary Outcome Measures :
  1. Percentage of Participants Who Experience Venous Thromboembolism Events (VTE) or Death From Any Cause During the Extension Treatment Period [ Time Frame: From randomization up to 24 days after randomization or the day of mandatory venography, whichever comes first ]
    VTE include any 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 suspected VTE. All-cause deaths include fatal PE and deaths for other reason than PE.


Secondary Outcome Measures :
  1. Percentage of Participants Who Experience "Major" VTE or Death From Any Cause [ Time Frame: From randomization up to 24 days after randomization or the day of mandatory venography, whichever comes first ]
    "Major" VTE include any proximal DVT, symptomatic distal DVT and non-fatal PE as confirmed by the CIAC.

  2. Percentage of Participants Who Experience Clinically Relevant Bleedings During the Extension Treatment Period [ Time Frame: From 1st study drug injection in the extension treatment period up to 3 days after last study drug injection ]

    Bleedings are 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 health care professional);

    "Non-clinically relevant bleeding".


  3. Percentage of Participants Who Require the Initiation of Curative Anticoagulant or Thrombolytic Treatment After VTE Assessment During the Extension Treatment Period [ Time Frame: From randomization up to 24 days after randomization or the day of mandatory venography, whichever comes first ]
    Initiation of curative anticoagulant or thrombolytic treatment after VTE assessment is 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:
  1. Overview of Reported Bleeding Adverse Event [ Time Frame: From 1st study drug injection up to 3 days after last study drug injection ]

    Analysis periods are defined as follows:

    • Initial treatment: time from the first study drug injection up to the first injection in the extension period or up to 3 days after the last injection if no extension treatment;
    • Extension treatment: time from first injection in the extension period up to 3 days after the last injection.

  2. Overview of Deaths [ Time Frame: From 1st study drug injection up to 3 days after last study drug injection ]
    The same analysis periods as defined for the previous outcome measure are used. In addition deaths during the extension treatment period are 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).

  3. Platelets Count: Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA) [ Time Frame: From 1st study drug injection up to 3 days after last study drug injection ]

    PCSA are abnormal values considered medically important by the Sponsor according to pre-defined criteria based on literature review. Threshold for platelets count was defined as <100 Giga/L.

    The analysis periods as previously defined are used (see outcome measure 5).


  4. Liver Function: Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA) [ Time Frame: From 1st study drug injection up to 3 days after last study drug injection ]

    Thresholds are defined as follows:

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

    Cases with ALT >3 ULN and TB >2 ULN (not necessarily concomitant) are evaluated by a blinded independent adjudicator to determine if they met Hy's law criteria.

    The analysis periods as previously defined are used (see outcome measure 5).




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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • In the run-in phase:

    • Standard surgery for fracture of the upper third of the femur, including femoral head and neck
  • In the double-blind phase following the run-in phase:

    • Completion of the run-in phase without permanent treatment discontinuation

Exclusion Criteria:

  • Any major orthopedic surgery within 3 months prior to enrolment;
  • Deep vein thrombosis or pulmonary embolism within the last 12 months, or known post-phlebitic syndrome;
  • High risk of bleeding;
  • Known hypersensitivity to heparins;
  • Any contraindication 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00709904


Locations
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United States, New Jersey
Sanofi-Aventis Administrative Office
Bridgewater, New Jersey, United States, 08807
Belarus
Sanofi-Aventis Administrative Office
Minsk, Belarus
Canada
Sanofi-Aventis Administrative Office
Laval, Canada
Chile
Sanofi-Aventis Administrative Office
Santiago, Chile
China
Sanofi-Aventis Administrative Office
Shangaï, China
Colombia
Sanofi-Aventis Administrative Office
Santafe de Bogota, Colombia
Egypt
Sanofi-Aventis Administrative Office
Cairo, Egypt
India
Sanofi-Aventis Administrative Office
Mumbai, India
Korea, Republic of
Sanofi-Aventis Administrative Office
Seoul, Korea, Republic of
Lithuania
Sanofi-Aventis Administrative Office
Vilnius, Lithuania
Mexico
Sanofi-Aventis Administrative Office
Mexico, Mexico
Peru
Sanofi-Aventis Administrative Office
Lima, Peru
Russian Federation
Sanofi-Aventis Administrative Office
Moscow, Russian Federation
South Africa
Sanofi-Aventis Administrative Office
Midrand, South Africa
Turkey
Sanofi-Aventis Administrative Office
Istanbul, Turkey
Ukraine
Sanofi-Aventis Administrative Office
Kiev, Ukraine
Sponsors and Collaborators
Sanofi
Investigators
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Principal Investigator: William D. Fisher, MD McGill University Health Centre, Montreal, Quebec, Canada
Study Chair: Alexander G. Turpie, MD HHS-General Hospital, Hamilton, Ontario, Canada

Publications of Results:
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Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00709904     History of Changes
Other Study ID Numbers: EFC10636
2007-007947-28 ( EudraCT Number )
First Posted: July 3, 2008    Key Record Dates
Last Update Posted: June 14, 2013
Last Verified: June 2013

Keywords provided by Sanofi:
venous thromboprophylaxis
primary prevention
orthopedic surgery

Additional relevant MeSH terms:
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Thromboembolism
Venous Thromboembolism
Hip Fractures
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Femoral Fractures
Fractures, Bone
Wounds and Injuries
Hip Injuries
Leg Injuries
Semuloparin
Heparin, Low-Molecular-Weight
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Anticoagulants