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

Venous Thromboembolism Clinical Trial

— 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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00721760
• Other study ID #: EFC10343
• Secondary ID: 2007-007945-11
• Status: Completed
• Phase: Phase 3
• First received: July 22, 2008
• Last updated: January 14, 2013
• Start date: July 2008
• Est. completion date: October 2009

Study information

• Verified date: January 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 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1003
• Est. completion date: October 2009
• Est. primary completion date: October 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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.

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:
• Enoxaparin sodium
0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe Subcutaneous injection
• Semuloparin sodium
0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe Subcutaneous injection
• 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

Locations

Country	Name	City	State
Argentina	Sanofi-Aventis Administrative Office	Buenos Aires
Belarus	Sanofi-Aventis Administrative Office	Minsk
Bulgaria	Sanofi-Aventis Administrative Office	Sofia
Canada	Sanofi-Aventis Administrative Office	Laval
Chile	Sanofi-Aventis Administrative Office	Santiago
China	Sanofi-Aventis Administrative Office	Shangaï
Colombia	Sanofi-Aventis Administrative Office	Bogota
Czech Republic	Sanofi-Aventis Administrative Office	Praha
Denmark	Sanofi-Aventis Administrative Office	Horsholm
Finland	Sanofi-Aventis Administrative Office	Helsinki
Greece	Sanofi-Aventis Administrative Office	Athens
India	Sanofi-Aventis Administrative Office	Mumbai
Italy	Sanofi-Aventis Administrative Office	Milano
Mexico	Sanofi-Aventis Administrative Office	Mexico
Peru	Sanofi-Aventis Administrative Office	Lima
Poland	Sanofi-Aventis Administrative Office	Warszawa
Portugal	Sanofi-Aventis Administrative Office	Porto Salvo
Romania	Sanofi-Aventis Administrative Office	Bucuresti
Russian Federation	Sanofi-Aventis Administrative Office	Moscow
South Africa	Sanofi-Aventis Administrative Office	Midrand
Spain	Sanofi-Aventis Administrative Office	Barcelona
Sweden	Sanofi-Aventis Administrative Office	Bromma
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,  Argentina,  Belarus,  Bulgaria,  Canada,  Chile,  China,  Colombia,  Czech Republic,  Denmark,  Finland,  Greece,  India,  Italy,  Mexico,  Peru,  Poland,  Portugal,  Romania,  Russian Federation,  South Africa,  Spain,  Sweden,  Turkey,  Ukraine, 

References & Publications (1)

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-HI — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Overview of deaths	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).	From first 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 predefined criteria based on literature review.; Threshold for platelet counts was defined as <100 Giga/L.	From first 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 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.	From first study drug injection up to 3 days after last study drug injection	Yes
Primary	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.	From randomization up to 10 days after surgery or the day of mandatory venography, whichever came first	No
Secondary	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.	From randomization up to 10 days after surgery or the day of mandatory venography, whichever came first	No
Secondary	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".	From first study drug injection up to 3 days after last study drug injection	Yes
Secondary	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.	From randomization up to 10 days after surgery or the day of mandatory venography, whichever came first	No