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

Primary Purpose

Venous Thromboembolism

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Enoxaparin sodium
Semuloparin sodium
Placebo
Sponsored by
Sanofi
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Venous Thromboembolism focused on measuring Hip fractures, Heparin Low-Molecular-Weight, Randomized Controlled Trial

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office
  • Sanofi-Aventis Administrative Office

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Semuloparin

Enoxaparin

Arm Description

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

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

Outcomes

Primary Outcome Measures

Percentage of Participants Who Experienced Venous Thromboembolism Event [VTE] or All-cause Death
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
"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
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
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.

Full Information

First Posted
July 22, 2008
Last Updated
January 14, 2013
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT00721760
Brief Title
Evaluation of AVE5026 as Compared to Enoxaparin for the Prevention of Thromboembolism in Patients Undergoing Hip Fracture Surgery
Acronym
SAVE-HIP2
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2013
Overall Recruitment Status
Completed
Study Start Date
July 2008 (undefined)
Primary Completion Date
October 2009 (Actual)
Study Completion Date
October 2009 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Sanofi

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Venous Thromboembolism
Keywords
Hip fractures, Heparin Low-Molecular-Weight, Randomized Controlled Trial

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 3
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
1003 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Semuloparin
Arm Type
Experimental
Arm Description
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
Arm Title
Enoxaparin
Arm Type
Active Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Enoxaparin sodium
Other Intervention Name(s)
Lovenox®
Intervention Description
0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe Subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Semuloparin sodium
Other Intervention Name(s)
AVE5026
Intervention Description
0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe Subcutaneous injection
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
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
Primary Outcome Measure Information:
Title
Percentage of Participants Who Experienced Venous Thromboembolism Event [VTE] or All-cause Death
Description
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.
Time Frame
From randomization up to 10 days after surgery or the day of mandatory venography, whichever came first
Secondary Outcome Measure Information:
Title
Percentage of Participants Who Experienced "Major" VTE or All-cause Death
Description
"major" VTE included any proximal DVT, symptomatic distal DVT and non-fatal PE as confirmed by the CIAC.
Time Frame
From randomization up to 10 days after surgery or the day of mandatory venography, whichever came first
Title
Percentage of Participants Who Experienced Clinically Relevant Bleedings
Description
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".
Time Frame
From first study drug injection up to 3 days after last study drug injection
Title
Percentage of Participants Who Required the Initiation of Curative Anticoagulant or Thrombolytic Treatment After VTE Assessment
Description
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.
Time Frame
From randomization up to 10 days after surgery or the day of mandatory venography, whichever came first
Other Pre-specified Outcome Measures:
Title
Overview of deaths
Description
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).
Time Frame
From first study drug injection up to 3 days after last study drug injection
Title
Platelets Count: Percentage of Participants With Potentially Clinically Significant Abnormalities [PCSA]
Description
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.
Time Frame
From first study drug injection up to 3 days after last study drug injection
Title
Liver Function: Percentage of Participants With Potentially Clinically Significant Abnormalities [PCSA]
Description
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.
Time Frame
From first study drug injection up to 3 days after last study drug injection

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William D. Fisher, MD
Organizational Affiliation
Department of Orthopaedic Surgery, McGill University Health Centre, 1650 Cedar Avenue, Montreal, Quebec, H3G 1A4, Canada
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Alexander G. Turpie
Organizational Affiliation
McMaster University
Official's Role
Study Chair
Facility Information:
Facility Name
Sanofi-Aventis Administrative Office
City
Bridgewater
State/Province
New Jersey
ZIP/Postal Code
08807
Country
United States
Facility Name
Sanofi-Aventis Administrative Office
City
Buenos Aires
Country
Argentina
Facility Name
Sanofi-Aventis Administrative Office
City
Minsk
Country
Belarus
Facility Name
Sanofi-Aventis Administrative Office
City
Sofia
Country
Bulgaria
Facility Name
Sanofi-Aventis Administrative Office
City
Laval
Country
Canada
Facility Name
Sanofi-Aventis Administrative Office
City
Santiago
Country
Chile
Facility Name
Sanofi-Aventis Administrative Office
City
Shangaï
Country
China
Facility Name
Sanofi-Aventis Administrative Office
City
Bogota
Country
Colombia
Facility Name
Sanofi-Aventis Administrative Office
City
Praha
Country
Czech Republic
Facility Name
Sanofi-Aventis Administrative Office
City
Horsholm
Country
Denmark
Facility Name
Sanofi-Aventis Administrative Office
City
Helsinki
Country
Finland
Facility Name
Sanofi-Aventis Administrative Office
City
Athens
Country
Greece
Facility Name
Sanofi-Aventis Administrative Office
City
Mumbai
Country
India
Facility Name
Sanofi-Aventis Administrative Office
City
Milano
Country
Italy
Facility Name
Sanofi-Aventis Administrative Office
City
Mexico
Country
Mexico
Facility Name
Sanofi-Aventis Administrative Office
City
Lima
Country
Peru
Facility Name
Sanofi-Aventis Administrative Office
City
Warszawa
Country
Poland
Facility Name
Sanofi-Aventis Administrative Office
City
Porto Salvo
Country
Portugal
Facility Name
Sanofi-Aventis Administrative Office
City
Bucuresti
Country
Romania
Facility Name
Sanofi-Aventis Administrative Office
City
Moscow
Country
Russian Federation
Facility Name
Sanofi-Aventis Administrative Office
City
Midrand
Country
South Africa
Facility Name
Sanofi-Aventis Administrative Office
City
Barcelona
Country
Spain
Facility Name
Sanofi-Aventis Administrative Office
City
Bromma
Country
Sweden
Facility Name
Sanofi-Aventis Administrative Office
City
Istanbul
Country
Turkey
Facility Name
Sanofi-Aventis Administrative Office
City
Kiev
Country
Ukraine

12. IPD Sharing Statement

Citations:
PubMed Identifier
22429800
Citation
Lassen MR, Fisher W, Mouret P, Agnelli G, George D, Kakkar A, Mismetti P, Turpie AG; SAVE Investigators. Semuloparin for prevention of venous thromboembolism after major orthopedic surgery: results from three randomized clinical trials, SAVE-HIP1, SAVE-HIP2 and SAVE-KNEE. J Thromb Haemost. 2012 May;10(5):822-32. doi: 10.1111/j.1538-7836.2012.04701.x.
Results Reference
result

Learn more about this trial

Evaluation of AVE5026 as Compared to Enoxaparin for the Prevention of Thromboembolism in Patients Undergoing Hip Fracture Surgery

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