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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)

Primary Purpose

Venous Thromboembolism

Status
Completed
Phase
Phase 3
Locations
International
Study Type
Interventional
Intervention
Open-label Semuloparin sodium
Placebo (for Semuloparin sodium)
Semuloparin sodium
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 venous thromboprophylaxis, primary prevention, orthopedic surgery

Eligibility Criteria

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

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.

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

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Semuloparin extension treatment

Placebo extension treatment

Arm Description

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.

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

Outcomes

Primary Outcome Measures

Percentage of Participants Who Experience Venous Thromboembolism Events (VTE) or Death From Any Cause During the Extension Treatment Period
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

Percentage of Participants Who Experience "Major" VTE or Death From Any Cause
"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
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
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.

Full Information

First Posted
July 1, 2008
Last Updated
June 6, 2013
Sponsor
Sanofi
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1. Study Identification

Unique Protocol Identification Number
NCT00709904
Brief Title
Evaluation of AVE5026 as Compared to Placebo for the Extended Prophylaxis of Venous Thromboembolism in Patients Having Undergone Hip Fracture Surgery
Acronym
SAVE-HIP3
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 Type
Interventional

2. Study Status

Record Verification Date
June 2013
Overall Recruitment Status
Completed
Study Start Date
June 2008 (undefined)
Primary Completion Date
January 2010 (Actual)
Study Completion Date
January 2010 (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 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Venous Thromboembolism
Keywords
venous thromboprophylaxis, primary prevention, orthopedic surgery

7. Study Design

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

8. Arms, Groups, and Interventions

Arm Title
Semuloparin extension treatment
Arm Type
Experimental
Arm Description
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.
Arm Title
Placebo extension treatment
Arm Type
Placebo Comparator
Arm Description
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
Intervention Type
Drug
Intervention Name(s)
Open-label 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 once daily with an initial dose given 8 hours after surgery
Intervention Type
Drug
Intervention Name(s)
Placebo (for Semuloparin sodium)
Intervention Description
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
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 once daily
Primary Outcome Measure Information:
Title
Percentage of Participants Who Experience Venous Thromboembolism Events (VTE) or Death From Any Cause During the Extension Treatment Period
Description
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.
Time Frame
From randomization up to 24 days after randomization or the day of mandatory venography, whichever comes first
Secondary Outcome Measure Information:
Title
Percentage of Participants Who Experience "Major" VTE or Death From Any Cause
Description
"Major" VTE include any proximal DVT, symptomatic distal DVT and non-fatal PE as confirmed by the CIAC.
Time Frame
From randomization up to 24 days after randomization or the day of mandatory venography, whichever comes first
Title
Percentage of Participants Who Experience Clinically Relevant Bleedings During the Extension Treatment Period
Description
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".
Time Frame
From 1st study drug injection in the extension treatment period up to 3 days after last study drug injection
Title
Percentage of Participants Who Require the Initiation of Curative Anticoagulant or Thrombolytic Treatment After VTE Assessment During the Extension Treatment Period
Description
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.
Time Frame
From randomization up to 24 days after randomization or the day of mandatory venography, whichever comes first
Other Pre-specified Outcome Measures:
Title
Overview of Reported Bleeding Adverse Event
Description
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.
Time Frame
From 1st study drug injection up to 3 days after last study drug injection
Title
Overview of Deaths
Description
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).
Time Frame
From 1st 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 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).
Time Frame
From 1st 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 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).
Time Frame
From 1st 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: 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
William D. Fisher, MD
Organizational Affiliation
McGill University Health Centre, Montreal, Quebec, Canada
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Alexander G. Turpie, MD
Organizational Affiliation
HHS-General Hospital, Hamilton, Ontario, Canada
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
Minsk
Country
Belarus
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
Santafe de Bogota
Country
Colombia
Facility Name
Sanofi-Aventis Administrative Office
City
Cairo
Country
Egypt
Facility Name
Sanofi-Aventis Administrative Office
City
Mumbai
Country
India
Facility Name
Sanofi-Aventis Administrative Office
City
Seoul
Country
Korea, Republic of
Facility Name
Sanofi-Aventis Administrative Office
City
Vilnius
Country
Lithuania
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
Moscow
Country
Russian Federation
Facility Name
Sanofi-Aventis Administrative Office
City
Midrand
Country
South Africa
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
23539696
Citation
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.
Results Reference
result

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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

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