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Evaluation of AVE5026 as Compared to Enoxaparin for the Prevention of Thromboembolism in Patients Undergoing Hip Fracture Surgery (SAVE-HIP2)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00721760
First received: July 22, 2008
Last updated: January 14, 2013
Last verified: January 2013
History of Changes
  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 hip fracture surgery.

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


Condition Intervention Phase
Venous Thromboembolism
 Drug: Enoxaparin sodium
Drug: Semuloparin 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 Hip Fracture Surgery

Resource links provided by NLM:

U.S. FDA Resources

Further study details as provided by Sanofi:

Primary Outcome Measures:
  • Percentage of Participants Who Experienced Venous Thromboembolism Event [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 ]

    VTE included any Deep Vein Thrombosis [DVT] (proximal or distal, 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 non-fatal 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 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: 1003
Study Start Date: July 2008
Study Completion Date: October 2009
Primary Completion Date: October 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 prefilled 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 prefilled syringe strictly identical in appearance but without active component

Subcutaneous injection

Detailed Description:

Randomization had to take place just prior to 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 between 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:

  • Standard surgery for fracture of the upper third of the femur including femoral head and neck.

Exclusion Criteria:

  • Estimated time of injury/fracture > 24 hours before admission to hospital;
  • Any major orthopedic surgery in the 3 months prior to study start;
  • Multiple trauma affecting more than one organ system;
  • 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, or pork products;
  • 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00721760

  Show 25 Study Locations
Sponsors and Collaborators
Sanofi
Investigators
Principal Investigator: William D. Fisher, MD Department of Orthopaedic Surgery, McGill University Health Centre, 1650 Cedar Avenue, Montreal, Quebec, H3G 1A4, Canada
Study Chair: Alexander G. Turpie McMaster University
  More Information

Publications:

Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00721760     History of Changes
Other Study ID Numbers: EFC10343, 2007-007945-11
Study First Received: July 22, 2008
Last Updated: January 14, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanofi:
Hip fractures
Heparin Low-Molecular-Weight
Randomized Controlled Trial

Additional relevant MeSH terms:
Hip Fractures
Thromboembolism
Venous Thromboembolism
Venous Thrombosis
Femoral Fractures
Fractures, Bone
Wounds and Injuries
Hip Injuries
Leg Injuries
Embolism and Thrombosis
Vascular Diseases
 Cardiovascular Diseases
Thrombosis
Enoxaparin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on May 19, 2013