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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)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
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

Tracking Information
First Submitted Date  ICMJE July 1, 2008
First Posted Date  ICMJE July 3, 2008
Last Update Posted Date June 14, 2013
Study Start Date  ICMJE June 2008
Actual Primary Completion Date January 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 6, 2013)
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.
Original Primary Outcome Measures  ICMJE
 (submitted: July 1, 2008)
Composite of any VTE and death from any cause [ Time Frame: From randomization up to the day of a venous thromboembolic event or the day of the mandatory venography, whichever comes first ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: June 6, 2013)
  • 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.
  • 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".
  • 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.
Original Secondary Outcome Measures  ICMJE
 (submitted: July 1, 2008)
  • Composite of any proximal deep vein thrombosis, symptomatic distal deep vein thrombosis, non-fatal pulmonary embolism and all-cause deaths [ Time Frame: From randomization up to the day of a venous thromboembolic event or the day of the mandatory venography, whichever comes first ]
  • Safety:bleeding events, transfusions, laboratory data, adverse events, deaths [ Time Frame: Study period ]
Current Other Pre-specified Outcome Measures
 (submitted: June 6, 2013)
  • 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.
  • 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).
  • 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).
  • 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).
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Evaluation of AVE5026 as Compared to Placebo for the Extended Prophylaxis of Venous Thromboembolism in Patients Having Undergone Hip Fracture Surgery
Official Title  ICMJE 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
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.

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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Condition  ICMJE Venous Thromboembolism
Intervention  ICMJE
  • 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

  • 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
Study Arms  ICMJE
  • 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.
    Interventions:
    • Drug: Open-label Semuloparin sodium
    • Drug: Semuloparin sodium
  • 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
    Interventions:
    • Drug: Open-label Semuloparin sodium
    • Drug: Placebo (for Semuloparin sodium)
Publications * Fisher WD, Agnelli G, George DJ, Kakkar AK, Lassen MR, Mismetti P, Mouret P, Turpie AG. Extended venous thromboembolism prophylaxis in patients undergoing hip fracture surgery - the SAVE-HIP3 study. Bone Joint J. 2013 Apr;95-B(4):459-66. doi: 10.1302/0301-620X.95B4.30730.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: November 26, 2010)
469
Original Estimated Enrollment  ICMJE
 (submitted: July 1, 2008)
454
Actual Study Completion Date  ICMJE January 2010
Actual Primary Completion Date January 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Belarus,   Canada,   Chile,   China,   Colombia,   Egypt,   India,   Korea, Republic of,   Lithuania,   Mexico,   Peru,   Russian Federation,   South Africa,   Turkey,   Ukraine,   United States
Removed Location Countries Brazil
 
Administrative Information
NCT Number  ICMJE NCT00709904
Other Study ID Numbers  ICMJE EFC10636
2007-007947-28 ( EudraCT Number )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sanofi
Study Sponsor  ICMJE Sanofi
Collaborators  ICMJE Not Provided
Investigators  ICMJE
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
PRS Account Sanofi
Verification Date June 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP