Evaluation of AVE5026 as Compared to Enoxaparin for the Prevention of Venous Thromboembolism in Patients Undergoing Major Abdominal Surgery

Venous Thromboembolism Clinical Trial

— SAVE-ABDO  

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 Major Abdominal Surgery

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00679588
• Other study ID #: EFC6520
• Secondary ID: 2007-007942-36
• Status: Completed
• Phase: Phase 3
• First received: May 7, 2008
• Last updated: November 21, 2013
• Start date: April 2008
• Est. completion date: August 2010

Study information

• Verified date: November 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 compare the efficacy and safety 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 major abdominal surgery.

The secondary objectives are to evaluate the safety of Semuloparin sodium (AVE5026) and to document Semuloparin sodium (AVE5026) exposure in this population.

Description:

Randomization has to take place prior to the surgery.

The total duration of observation per participant is 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 has to be performed between 7 to 11 days after surgery.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 4413
• Est. completion date: August 2010
• Est. primary completion date: August 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Patient undergoing major abdominal surgery (open surgery under general anesthesia lasting more than 45 minutes in the peritoneal and/or retroperitoneal space and/or pelvis).

• Patient <60 years of age had to have one of the following additional risk factors for VTE:

• History of VTE,

• Obesity,

• Chronic Heart failure,

• Chronic Respiratory Failure,

• Inflammatory Bowel Disease,

• Cancer Surgery.

Exclusion Criteria:

• Any major orthopedic or general surgery in the 3 months prior to study start;

• Clinical signs or symptoms of DVT or PE within the last 12 months or known post phlebitic syndrome;

• Any contra-indications to the performance of venography;

• High risk of bleeding;

• Known hypersensitivity to heparin or Enoxaparin sodium;

• End stage renal disease or patient on dialysis.

The above information was 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

• Thromboembolism
• Venous Thromboembolism

Intervention

Drug:
• Semuloparin Sodium
0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe Subcutaneous injection
• Enoxaparin 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 containing the same volume but without active component Subcutaneous injection

Locations

Country	Name	City	State
Argentina	Investigational Site Number 032001	Buenos Aires
Argentina	Investigational Site Number 032002	Buenos Aires
Argentina	Investigational Site Number 032004	Buenos Aires
Argentina	Investigational Site Number 032007	Capital Federal
Argentina	Investigational Site Number 032008	Capital Federal
Argentina	Investigational Site Number 032014	Córdoba
Argentina	Investigational Site Number 032012	Rosario
Argentina	Investigational Site Number 032005	Santa Fe
Australia	Investigational Site Number 036002	Box Hill
Australia	Investigational Site Number 036003	Box Hill
Australia	Investigational Site Number 036001	Kogarah
Australia	Investigational Site Number 036008	Redcliffe
Austria	Investigational Site Number 040001	Graz
Austria	Investigational Site Number 040002	Wels
Belarus	Investigational Site Number 112001	Gomel
Belarus	Investigational Site Number 112006	Gomel
Belarus	Investigational Site Number 112002	Minsk
Belarus	Investigational Site Number 112003	Minsk
Belarus	Investigational Site Number 112005	Minsk
Belarus	Investigational Site Number 112008	Minsk
Belarus	Investigational Site Number 112004	Vitebsk
Belarus	Investigational Site Number 112007	Vitebsk
Belgium	Investigational Site Number 056002	Genk
Belgium	Investigational Site Number 056001	Gent
Brazil	Investigational Site Number 076003	Belo Horizonte
Brazil	Investigational Site Number 076010	Belo Horizonte
Brazil	Investigational Site Number 076014	Caxias Do Sul
Brazil	Investigational Site Number 076005	Curitiba
Brazil	Investigational Site Number 076012	Curitiba
Brazil	Investigational Site Number 076006	Goiania
Brazil	Investigational Site Number 076011	Joinville
Brazil	Investigational Site Number 076007	Porto Alegre
Brazil	Investigational Site Number 076009	Porto Alegre
Brazil	Investigational Site Number 076015	Ribeirao Preto
Brazil	Investigational Site Number 076013	Sao Jose Do Rio Preto
Brazil	Investigational Site Number 076002	Sao Paulo
Brazil	Investigational Site Number 076004	Sao Paulo
Brazil	Investigational Site Number 076008	Sao Paulo
Bulgaria	Investigational Site Number 100004	Pleven
Bulgaria	Investigational Site Number 100003	Ruse
Bulgaria	Investigational Site Number 100005	Sofia
Bulgaria	Investigational Site Number 100008	Sofia
Bulgaria	Investigational Site Number 100009	Sofia
Bulgaria	Investigational Site Number 100011	Sofia
Bulgaria	Investigational Site Number 100006	Varna
Bulgaria	Investigational Site Number 100010	Varna
Canada	Investigational Site Number 124001	Edmonton
Canada	Investigational Site Number 124004	Kitchener
Canada	Investigational Site Number 124010	Montreal
Canada	Investigational Site Number 124011	Red Deer
Canada	Investigational Site Number 124009	Saint John
Canada	Investigational Site Number 124002	Thunder Bay
Canada	Investigational Site Number 124007	Vancouver
Chile	Investigational Site Number 152002	Rancagua
Chile	Investigational Site Number 152001	Santiago
China	Investigational Site Number 156011	Baotou
China	Investigational Site Number 156010	Changsha
China	Investigational Site Number 156012	Changsha
China	Investigational Site Number 156006	Fuzhou
China	Investigational Site Number 156003	Guangzhou
China	Investigational Site Number 156013	Haikou
China	Investigational Site Number 156005	Nanjing
China	Investigational Site Number 156008	Qingdao
China	Investigational Site Number 156001	Shijiazhuang
China	Investigational Site Number 156014	Tianjin
China	Investigational Site Number 156004	Xi'An
Croatia	Investigational Site Number 191004	Pozega
Croatia	Investigational Site Number 191001	Pula
Croatia	Investigational Site Number 191002	Zagreb
Czech Republic	Investigational Site Number 203001	Brno
Czech Republic	Investigational Site Number 203007	Brno
Czech Republic	Investigational Site Number 203011	Jihlava
Czech Republic	Investigational Site Number 203015	Kolin
Czech Republic	Investigational Site Number 203009	Kromeriz
Czech Republic	Investigational Site Number 203004	Liberec
Czech Republic	Investigational Site Number 203014	Most
Czech Republic	Investigational Site Number 203003	Ostrava
Czech Republic	Investigational Site Number 203012	Pardubice
Czech Republic	Investigational Site Number 203008	Praha 4
Czech Republic	Investigational Site Number 203006	Praha 5
Czech Republic	Investigational Site Number 203002	Praha 6
Czech Republic	Investigational Site Number 203016	Ricany
Czech Republic	Investigational Site Number 203010	Usti Nad Labem
Denmark	Investigational Site Number 208001	København Nv
Denmark	Investigational Site Number 208002	Odense C
Estonia	Investigational Site Number 233003	Tallinn
Estonia	Investigational Site Number 233001	Tartu
Estonia	Investigational Site Number 233002	Tartu
Germany	Investigational Site Number 276011	Bochum
Germany	Investigational Site Number 276015	Castrop-Rauxel
Germany	Investigational Site Number 276018	Castrop-Rauxel
Germany	Investigational Site Number 276006	Dresden
Germany	Investigational Site Number 276012	Hannover
Germany	Investigational Site Number 276002	Heidelberg
Germany	Investigational Site Number 276004	Homburg
Germany	Investigational Site Number 276014	Lübeck
Germany	Investigational Site Number 276016	Magdeburg
Germany	Investigational Site Number 276013	München
Germany	Investigational Site Number 276001	Stralsund
Greece	Investigational Site Number 300002	Heraklion
Hungary	Investigational Site Number 348007	Debrecen
Hungary	Investigational Site Number 348009	Kistarcsa
Hungary	Investigational Site Number 348008	Szeged
Hungary	Investigational Site Number 348004	Szekesfehervar
Hungary	Investigational Site Number 348003	Szolnok
India	Investigational Site Number 356004	Ahmedabad
India	Investigational Site Number 356005	Ahmedabad
India	Investigational Site Number 356033	Andhra Pradesh
India	Investigational Site Number 356008	Bangalore
India	Investigational Site Number 356011	Bangalore
India	Investigational Site Number 356027	Bangalore
India	Investigational Site Number 356019	Banglore
India	Investigational Site Number 356031	Bhopal
India	Investigational Site Number 356014	Chennai
India	Investigational Site Number 356016	Chennai
India	Investigational Site Number 356018	Chennai
India	Investigational Site Number 356021	Chennai
India	Investigational Site Number 356013	Cochin
India	Investigational Site Number 356006	Coimbatore
India	Investigational Site Number 356025	Gujarat
India	Investigational Site Number 356010	Hyderabad
India	Investigational Site Number 356028	Hyderabad
India	Investigational Site Number 356002	Jaipur
India	Investigational Site Number 356022	Jaipur
India	Investigational Site Number 356007	Kochi
India	Investigational Site Number 356026	Lucknow
India	Investigational Site Number 356032	Ludhiana
India	Investigational Site Number 356003	Luknow
India	Investigational Site Number 356001	Mangalore
India	Investigational Site Number 356030	Nagpur
India	Investigational Site Number 356009	New Delhi
India	Investigational Site Number 356015	Pune
India	Investigational Site Number 356023	Pune
India	Investigational Site Number 356012	Punjgutta
Italy	Investigational Site Number 380009	Aviano
Italy	Investigational Site Number 380001	Genova
Italy	Investigational Site Number 380015	Genova
Italy	Investigational Site Number 380006	Milano
Italy	Investigational Site Number 380004	Padova
Italy	Investigational Site Number 380008	Parma
Italy	Investigational Site Number 380013	Piacenza
Italy	Investigational Site Number 380012	Pordenone
Italy	Investigational Site Number 380005	Reggio Emilia
Italy	Investigational Site Number 380011	San Donato Milanese
Italy	Investigational Site Number 380007	Trieste
Korea, Republic of	Investigational Site Number 410007	Daegu
Korea, Republic of	Investigational Site Number 410006	Goyang
Korea, Republic of	Investigational Site Number 410001	Gyeonggi-do
Korea, Republic of	Investigational Site Number 410009	Incheon
Korea, Republic of	Investigational Site Number 410002	Seoul
Korea, Republic of	Investigational Site Number 410004	Seoul
Korea, Republic of	Investigational Site Number 410008	Seoul
Korea, Republic of	Investigational Site Number 410010	Seoul
Korea, Republic of	Investigational Site Number 410011	Seoul
Korea, Republic of	Investigational Site Number 410003	Suwon
Latvia	Investigational Site Number 428004	Daugavpils
Latvia	Investigational Site Number 428002	Riga
Latvia	Investigational Site Number 428003	Riga
Lithuania	Investigational Site Number 440001	Kaunas
Lithuania	Investigational Site Number 440003	Kaunas
Lithuania	Investigational Site Number 440002	Vilnius
Mexico	Investigational Site Number 484001	Guadalajara
Mexico	Investigational Site Number 484006	Mazatlán
New Zealand	Investigational Site Number 554001	Christchurch
New Zealand	Investigational Site Number 554003	Christchurch
New Zealand	Investigational Site Number 554002	Nelson South
Norway	Investigational Site Number 578001	Trondheim
Peru	Investigational Site Number 604003	Callao
Peru	Investigational Site Number 604004	Callao
Peru	Investigational Site Number 604001	Lima
Peru	Investigational Site Number 604002	Lima
Peru	Investigational Site Number 604005	Lima
Peru	Investigational Site Number 604006	Lima
Poland	Investigational Site Number 616001	Bydgoszcz
Poland	Investigational Site Number 616003	Bydgoszcz
Poland	Investigational Site Number 616006	Gdansk
Poland	Investigational Site Number 616005	Krakow
Poland	Investigational Site Number 616018	Krakow
Poland	Investigational Site Number 616020	Krakow
Poland	Investigational Site Number 616002	Lodz
Poland	Investigational Site Number 616009	Lodz
Poland	Investigational Site Number 616010	Lublin
Poland	Investigational Site Number 616012	Poznan
Poland	Investigational Site Number 616015	Sosnowiec
Poland	Investigational Site Number 616013	Szczecin
Poland	Investigational Site Number 616011	Torun
Poland	Investigational Site Number 616004	Warszawa
Poland	Investigational Site Number 616014	Warszawa
Poland	Investigational Site Number 616007	Wroclaw
Poland	Investigational Site Number 616008	Wroclaw
Poland	Investigational Site Number 616016	Wroclaw
Romania	Investigational Site Number 642003	Cluj-Napoca
Romania	Investigational Site Number 642005	Cluj-Napoca
Romania	Investigational Site Number 642006	Cluj-Napoca
Romania	Investigational Site Number 642001	Oradea
Romania	Investigational Site Number 642004	Oradea
Romania	Investigational Site Number 642002	Timisoara
Russian Federation	Investigational Site Number 643019	Krasnodar
Russian Federation	Investigational Site Number 643006	Krasnoyarsk
Russian Federation	Investigational Site Number 643001	Moscow
Russian Federation	Investigational Site Number 643002	Moscow
Russian Federation	Investigational Site Number 643003	Moscow
Russian Federation	Investigational Site Number 643020	Moscow
Russian Federation	Investigational Site Number 643021	Moscow
Russian Federation	Investigational Site Number 643025	Moscow
Russian Federation	Investigational Site Number 643007	Novosibirsk
Russian Federation	Investigational Site Number 643008	Novosibirsk
Russian Federation	Investigational Site Number 643026	Omsk
Russian Federation	Investigational Site Number 643015	Sestroretsk,
Russian Federation	Investigational Site Number 643011	St-Petersburg
Russian Federation	Investigational Site Number 643017	St-Petersburg
Russian Federation	Investigational Site Number 643018	St-Petersburg
Russian Federation	Investigational Site Number 643010	St. Petersburg
Russian Federation	Investigational Site Number 643009	St.-Petersburg
Russian Federation	Investigational Site Number 643012	Tomsk
Russian Federation	Investigational Site Number 643016	Vsevolozhsk
Russian Federation	Investigational Site Number 643014	Yaroslavl
Serbia	Investigational Site Number 688001	Belgrade
Serbia	Investigational Site Number 688004	Belgrade
Serbia	Investigational Site Number 688002	Novi Sad
Slovakia	Investigational Site Number 703001	Bratislava
Slovenia	Investigational Site Number 705001	Celje
Slovenia	Investigational Site Number 705002	Maribor
South Africa	Investigational Site Number 710001	Cape Town
South Africa	Investigational Site Number 710004	Cape Town
South Africa	Investigational Site Number 710003	Worcester
Spain	Investigational Site Number 724001	Barcelona
Spain	Investigational Site Number 724002	Madrid
Sweden	Investigational Site Number 752002	Kungälv
Sweden	Investigational Site Number 752004	Norrköping
Sweden	Investigational Site Number 752001	Stockholm
Sweden	Investigational Site Number 752003	Varberg
Turkey	Investigational Site Number 792001	Istanbul
Turkey	Investigational Site Number 792003	Istanbul
Turkey	Investigational Site Number 792006	Istanbul
Turkey	Investigational Site Number 792007	Izmir
Ukraine	Investigational Site Number 804003	Cherkasy
Ukraine	Investigational Site Number 804007	Donetsk
Ukraine	Investigational Site Number 804010	Donetsk
Ukraine	Investigational Site Number 804011	Kharkiv
Ukraine	Investigational Site Number 804002	Kyiv
Ukraine	Investigational Site Number 804004	Kyiv
Ukraine	Investigational Site Number 804005	Kyiv
Ukraine	Investigational Site Number 804008	Odessa
United Kingdom	Investigational Site Number 826001	London
United States	Investigational Site Number 840002	Birmingham	Alabama
United States	Investigational Site Number 840026	Birmingham	Alabama
United States	Investigational Site Number 840035	Birmingham	Alabama
United States	Investigational Site Number 840042	Birmingham	Alabama
United States	Investigational Site Number 840029	Clearwater	Florida
United States	Investigational Site Number 840009	Columbus	Georgia
United States	Investigational Site Number 840051	Columbus	Ohio
United States	Investigational Site Number 840031	Corlton	California
United States	Investigational Site Number 840021	Denver	Colorado
United States	Investigational Site Number 840037	Hazard	Kentucky
United States	Investigational Site Number 840025	Houston	Texas
United States	Investigational Site Number 840050	Houston	Texas
United States	Investigational Site Number 840007	Huntingdon Beach	California
United States	Investigational Site Number 840017	Jacksonville	Florida
United States	Investigational Site Number 840014	Los Angeles	California
United States	Investigational Site Number 840032	Lubbock	Texas
United States	Investigational Site Number 840019	Maywood	Illinois
United States	Investigational Site Number 840044	Miami	Florida
United States	Investigational Site Number 840043	Morgantown	West Virginia
United States	Investigational Site Number 840015	Orlando	Florida
United States	Investigational Site Number 840006	Pittsburgh	Pennsylvania
United States	Investigational Site Number 840011	Sant Barbara	California
United States	Investigational Site Number 840036	Springfield	Illinois
United States	Investigational Site Number 840008	St Louis	Missouri
United States	Investigational Site Number 840020	Teaneck	New Jersey

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Argentina,  Australia,  Austria,  Belarus,  Belgium,  Brazil,  Bulgaria,  Canada,  Chile,  China,  Croatia,  Czech Republic,  Denmark,  Estonia,  Germany,  Greece,  Hungary,  India,  Italy,  Korea, Republic of,  Latvia,  Lithuania,  Mexico,  New Zealand,  Norway,  Peru,  Poland,  Romania,  Russian Federation,  Serbia,  Slovakia,  Slovenia,  South Africa,  Spain,  Sweden,  Turkey,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Number of Deaths on Treatment	All deaths 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 predefined criteria based on literature review.; Thresholds for platelet counts are defined as <100 Giga/L.	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.	From 1st study drug injection up to 3 days after last study drug injection	Yes
Other	Trough Plasma Concentration of Semuloparin Sodium (AVE5026)	Trough Plasma Concentration [Ctrough] is defined as plasma concentrations obtained just before study drug injection (i.e.24h±2h after study drug injection).; Lower Limit Of Quantification (LLOQ) is defined as 0,348 µgEq/mL. Concentrations below LLOQ are replaced by half of LLOQ for the calculation.	0.5-1 and 2-4 hours after Day 1 first post-operative injection, 6-8 and 10-16 hours after Day 4 injection, and just before the last injection	No
Primary	Percentage of Participants Who Experience Venous Thromboembolism Event (VTE) or All-cause Death	VTE includes any proximal or distal 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 VTE.; All-cause deaths includes fatal PE and deaths for other reason than PE.	From randomization up to 10 days after surgery or the day of mandatory venography, whichever comes first	No
Secondary	Percentage of Participants Who Experience "major" VTE or All-cause Death	"major" VTE includes any proximal DVT, symptomatic distal DVT and non-fatal Pulmonary Embolism (PE) as as confirmed by the CIAC.	From randomization up to 10 days after surgery or the day of mandatory venography, whichever comes first	No
Secondary	Percentage of Participants Who Experience Clinically Relevant Bleedings ("major" and "clinically relevant non-major" bleedings )	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); "Nonclinically relevant bleeding".	From 1st study drug injection up to 3 days after last study drug injection	Yes
Secondary	Percentage of Participants requiring 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 comes first	No