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

Venous Thromboembolism Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00709904
• Other study ID #: EFC10636
• Secondary ID: 2007-007947-28
• Status: Completed
• Phase: Phase 3
• First received: July 1, 2008
• Last updated: June 6, 2013
• Start date: June 2008
• Est. completion date: January 2010

Study information

• Verified date: June 2013
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 469
• Est. completion date: January 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Hip Fractures
• Thromboembolism
• Venous Thromboembolism

Intervention

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
• 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
• 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

Locations

Country	Name	City	State
Belarus	Sanofi-Aventis Administrative Office	Minsk
Canada	Sanofi-Aventis Administrative Office	Laval
Chile	Sanofi-Aventis Administrative Office	Santiago
China	Sanofi-Aventis Administrative Office	Shangaï
Colombia	Sanofi-Aventis Administrative Office	Santafe de Bogota
Egypt	Sanofi-Aventis Administrative Office	Cairo
India	Sanofi-Aventis Administrative Office	Mumbai
Korea, Republic of	Sanofi-Aventis Administrative Office	Seoul
Lithuania	Sanofi-Aventis Administrative Office	Vilnius
Mexico	Sanofi-Aventis Administrative Office	Mexico
Peru	Sanofi-Aventis Administrative Office	Lima
Russian Federation	Sanofi-Aventis Administrative Office	Moscow
South Africa	Sanofi-Aventis Administrative Office	Midrand
Turkey	Sanofi-Aventis Administrative Office	Istanbul
Ukraine	Sanofi-Aventis Administrative Office	Kiev
United States	Sanofi-Aventis Administrative Office	Bridgewater	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Belarus,  Canada,  Chile,  China,  Colombia,  Egypt,  India,  Korea, Republic of,  Lithuania,  Mexico,  Peru,  Russian Federation,  South Africa,  Turkey,  Ukraine, 

References & Publications (1)

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 — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overview of Reported Bleeding Adverse Event	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.	From 1st study drug injection up to 3 days after last study drug injection	Yes
Other	Overview of Deaths	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).	From 1st study drug injection up to 3 days after last study drug injection	Yes
Other	Platelets Count: Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA)	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).	From 1st study drug injection up to 3 days after last study drug injection	Yes
Other	Liver Function: Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA)	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).	From 1st study drug injection up to 3 days after last study drug injection	Yes
Primary	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.	From randomization up to 24 days after randomization or the day of mandatory venography, whichever comes first	No
Secondary	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.	From randomization up to 24 days after randomization or the day of mandatory venography, whichever comes first	No
Secondary	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".	From 1st study drug injection in the extension treatment period up to 3 days after last study drug injection	Yes
Secondary	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.	From randomization up to 24 days after randomization or the day of mandatory venography, whichever comes first	No