Clinical trial NCT00679588: Evaluation of AVE5026 as Compared to Enoxaparin for the Prevention of Venous Thromboembolism in Patients Undergoing Major Abdominal Surgery
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Venous Thromboembolism
Keywords: Digestive System Surgical Procedure
Urologic Surgical Procedure
Prevention of venous thromboembolism
Abdominal surgery
Lead sponsor: Sanofi
Sponsor class: INDUSTRY
First posted: 2008-05-19
Enrollment: 4413
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief 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.

Detailed 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants Who Experience Venous Thromboembolism Event (VTE) or All-cause Death
timeFrame: From randomization up to 10 days after surgery or the day of mandatory venography, whichever comes first
Secondary outcomes:
measure: Percentage of Participants Who Experience "major" VTE or All-cause Death
timeFrame: From randomization up to 10 days after surgery or the day of mandatory venography, whichever comes first
measure: Percentage of Participants Who Experience Clinically Relevant Bleedings ("major" and "clinically relevant non-major" bleedings )
timeFrame: From 1st study drug injection up to 3 days after last study drug injection
measure: Percentage of Participants requiring the initiation of curative anticoagulant or thrombolytic treatment after VTE assessment
timeFrame: From randomization up to 10 days after surgery or the day of mandatory venography, whichever comes first
Other outcomes:
measure: Number of Deaths on Treatment
timeFrame: From 1st study drug injection up to 3 days after last study drug injection
measure: Platelets Count: Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA)
timeFrame: From 1st study drug injection up to 3 days after last study drug injection
measure: Liver Function: Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA)
timeFrame: From 1st study drug injection up to 3 days after last study drug injection
measure: Trough Plasma Concentration of Semuloparin Sodium (AVE5026)
timeFrame: 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
Locations:
city: Birmingham
country: United States
facility: Investigational Site Number 840026
state: Alabama
city: Birmingham
country: United States
facility: Investigational Site Number 840035
state: Alabama
city: Birmingham
country: United States
facility: Investigational Site Number 840042
state: Alabama
city: Birmingham
country: United States
facility: Investigational Site Number 840002
state: Alabama
city: Corlton
country: United States
facility: Investigational Site Number 840031
state: California
city: Huntingdon Beach
country: United States
facility: Investigational Site Number 840007
state: California
city: Los Angeles
country: United States
facility: Investigational Site Number 840014
state: California
city: Sant Barbara
country: United States
facility: Investigational Site Number 840011
state: California
city: Denver
country: United States
facility: Investigational Site Number 840021
state: Colorado
city: Clearwater
country: United States
facility: Investigational Site Number 840029
state: Florida
city: Jacksonville
country: United States
facility: Investigational Site Number 840017
state: Florida
city: Miami
country: United States
facility: Investigational Site Number 840044
state: Florida
city: Orlando
country: United States
facility: Investigational Site Number 840015
state: Florida
city: Columbus
country: United States
facility: Investigational Site Number 840009
state: Georgia
city: Maywood
country: United States
facility: Investigational Site Number 840019
state: Illinois
city: Springfield
country: United States
facility: Investigational Site Number 840036
state: Illinois
city: Hazard
country: United States
facility: Investigational Site Number 840037
state: Kentucky
city: St Louis
country: United States
facility: Investigational Site Number 840008
state: Missouri
city: Teaneck
country: United States
facility: Investigational Site Number 840020
state: New Jersey
city: Columbus
country: United States
facility: Investigational Site Number 840051
state: Ohio
city: Pittsburgh
country: United States
facility: Investigational Site Number 840006
state: Pennsylvania
city: Houston
country: United States
facility: Investigational Site Number 840025
state: Texas
city: Houston
country: United States
facility: Investigational Site Number 840050
state: Texas
city: Lubbock
country: United States
facility: Investigational Site Number 840032
state: Texas
city: Morgantown
country: United States
facility: Investigational Site Number 840043
state: West Virginia
city: Buenos Aires
country: Argentina
facility: Investigational Site Number 032002
city: Buenos Aires
country: Argentina
facility: Investigational Site Number 032001
city: Buenos Aires
country: Argentina
facility: Investigational Site Number 032004
city: Capital Federal
country: Argentina
facility: Investigational Site Number 032007
city: Capital Federal
country: Argentina
facility: Investigational Site Number 032008
city: Córdoba
country: Argentina
facility: Investigational Site Number 032014
city: Rosario
country: Argentina
facility: Investigational Site Number 032012
city: Santa Fe
country: Argentina
facility: Investigational Site Number 032005
city: Box Hill
country: Australia
facility: Investigational Site Number 036002
city: Box Hill
country: Australia
facility: Investigational Site Number 036003
city: Kogarah
country: Australia
facility: Investigational Site Number 036001
city: Redcliffe
country: Australia
facility: Investigational Site Number 036008
city: Graz
country: Austria
facility: Investigational Site Number 040001
city: Wels
country: Austria
facility: Investigational Site Number 040002
city: Gomel
country: Belarus
facility: Investigational Site Number 112001
city: Gomel
country: Belarus
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city: Minsk
country: Belarus
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city: Minsk
country: Belarus
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city: Minsk
country: Belarus
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city: Minsk
country: Belarus
facility: Investigational Site Number 112005
city: Vitebsk
country: Belarus
facility: Investigational Site Number 112004
city: Vitebsk
country: Belarus
facility: Investigational Site Number 112007
city: Genk
country: Belgium
facility: Investigational Site Number 056002
city: Gent
country: Belgium
facility: Investigational Site Number 056001
city: Belo Horizonte
country: Brazil
facility: Investigational Site Number 076003
city: Belo Horizonte
country: Brazil
facility: Investigational Site Number 076010
city: Caxias Do Sul
country: Brazil
facility: Investigational Site Number 076014
city: Curitiba
country: Brazil
facility: Investigational Site Number 076012
city: Curitiba
country: Brazil
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city: Goiania
country: Brazil
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city: Joinville
country: Brazil
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country: Brazil
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city: Porto Alegre
country: Brazil
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city: Ribeirao Preto
country: Brazil
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city: Sao Jose Do Rio Preto
country: Brazil
facility: Investigational Site Number 076013
city: Sao Paulo
country: Brazil
facility: Investigational Site Number 076004
city: Sao Paulo
country: Brazil
facility: Investigational Site Number 076002
city: Sao Paulo
country: Brazil
facility: Investigational Site Number 076008
city: Pleven
country: Bulgaria
facility: Investigational Site Number 100004
city: Ruse
country: Bulgaria
facility: Investigational Site Number 100003
city: Sofia
country: Bulgaria
facility: Investigational Site Number 100011
city: Sofia
country: Bulgaria
facility: Investigational Site Number 100005
city: Sofia
country: Bulgaria
facility: Investigational Site Number 100008
city: Sofia
country: Bulgaria
facility: Investigational Site Number 100009
city: Varna
country: Bulgaria
facility: Investigational Site Number 100006
city: Varna
country: Bulgaria
facility: Investigational Site Number 100010
city: Edmonton
country: Canada
facility: Investigational Site Number 124001
city: Kitchener
country: Canada
facility: Investigational Site Number 124004
city: Montreal
country: Canada
facility: Investigational Site Number 124010
city: Red Deer
country: Canada
facility: Investigational Site Number 124011
city: Saint John
country: Canada
facility: Investigational Site Number 124009
city: Thunder Bay
country: Canada
facility: Investigational Site Number 124002
city: Vancouver
country: Canada
facility: Investigational Site Number 124007
city: Rancagua
country: Chile
facility: Investigational Site Number 152002
city: Santiago
country: Chile
facility: Investigational Site Number 152001
city: Baotou
country: China
facility: Investigational Site Number 156011
city: Changsha
country: China
facility: Investigational Site Number 156012
city: Changsha
country: China
facility: Investigational Site Number 156010
city: Fuzhou
country: China
facility: Investigational Site Number 156006
city: Guangzhou
country: China
facility: Investigational Site Number 156003
city: Haikou
country: China
facility: Investigational Site Number 156013
city: Nanjing
country: China
facility: Investigational Site Number 156005
city: Qingdao
country: China
facility: Investigational Site Number 156008
city: Shijiazhuang
country: China
facility: Investigational Site Number 156001
city: Tianjin
country: China
facility: Investigational Site Number 156014
city: Xi'An
country: China
facility: Investigational Site Number 156004
city: Pozega
country: Croatia
facility: Investigational Site Number 191004
city: Pula
country: Croatia
facility: Investigational Site Number 191001
city: Zagreb
country: Croatia
facility: Investigational Site Number 191002
city: Brno
country: Czech Republic
facility: Investigational Site Number 203007
city: Brno
country: Czech Republic
facility: Investigational Site Number 203001
city: Jihlava
country: Czech Republic
facility: Investigational Site Number 203011
city: Kolin
country: Czech Republic
facility: Investigational Site Number 203015
city: Kromeriz
country: Czech Republic
facility: Investigational Site Number 203009
city: Liberec
country: Czech Republic
facility: Investigational Site Number 203004
city: Most
country: Czech Republic
facility: Investigational Site Number 203014
city: Ostrava
country: Czech Republic
facility: Investigational Site Number 203003
city: Pardubice
country: Czech Republic
facility: Investigational Site Number 203012
city: Praha 4
country: Czech Republic
facility: Investigational Site Number 203008
city: Praha 5
country: Czech Republic
facility: Investigational Site Number 203006
city: Praha 6
country: Czech Republic
facility: Investigational Site Number 203002
city: Ricany
country: Czech Republic
facility: Investigational Site Number 203016
city: Usti Nad Labem
country: Czech Republic
facility: Investigational Site Number 203010
city: København Nv
country: Denmark
facility: Investigational Site Number 208001
city: Odense C
country: Denmark
facility: Investigational Site Number 208002
city: Tallinn
country: Estonia
facility: Investigational Site Number 233003
city: Tartu
country: Estonia
facility: Investigational Site Number 233001
city: Tartu
country: Estonia
facility: Investigational Site Number 233002
city: Bochum
country: Germany
facility: Investigational Site Number 276011
city: Castrop-Rauxel
country: Germany
facility: Investigational Site Number 276015
city: Castrop-Rauxel
country: Germany
facility: Investigational Site Number 276018
city: Dresden
country: Germany
facility: Investigational Site Number 276006
city: Hannover
country: Germany
facility: Investigational Site Number 276012
city: Heidelberg
country: Germany
facility: Investigational Site Number 276002
city: Homburg
country: Germany
facility: Investigational Site Number 276004
city: Lübeck
country: Germany
facility: Investigational Site Number 276014
city: Magdeburg
country: Germany
facility: Investigational Site Number 276016
city: München
country: Germany
facility: Investigational Site Number 276013
city: Stralsund
country: Germany
facility: Investigational Site Number 276001
city: Heraklion
country: Greece
facility: Investigational Site Number 300002
city: Debrecen
country: Hungary
facility: Investigational Site Number 348007
city: Kistarcsa
country: Hungary
facility: Investigational Site Number 348009
city: Szeged
country: Hungary
facility: Investigational Site Number 348008
city: Szekesfehervar
country: Hungary
facility: Investigational Site Number 348004
city: Szolnok
country: Hungary
facility: Investigational Site Number 348003
city: Ahmedabad
country: India
facility: Investigational Site Number 356005
city: Ahmedabad
country: India
facility: Investigational Site Number 356004
city: Andhra Pradesh
country: India
facility: Investigational Site Number 356033
city: Bangalore
country: India
facility: Investigational Site Number 356011
city: Bangalore
country: India
facility: Investigational Site Number 356027
city: Bangalore
country: India
facility: Investigational Site Number 356008
city: Banglore
country: India
facility: Investigational Site Number 356019
city: Bhopal
country: India
facility: Investigational Site Number 356031
city: Chennai
country: India
facility: Investigational Site Number 356014
city: Chennai
country: India
facility: Investigational Site Number 356018
city: Chennai
country: India
facility: Investigational Site Number 356016
city: Chennai
country: India
facility: Investigational Site Number 356021
city: Cochin
country: India
facility: Investigational Site Number 356013
city: Coimbatore
country: India
facility: Investigational Site Number 356006
city: Gujarat
country: India
facility: Investigational Site Number 356025
city: Hyderabad
country: India
facility: Investigational Site Number 356028
city: Hyderabad
country: India
facility: Investigational Site Number 356010
city: Jaipur
country: India
facility: Investigational Site Number 356002
city: Jaipur
country: India
facility: Investigational Site Number 356022
city: Kochi
country: India
facility: Investigational Site Number 356007
city: Lucknow
country: India
facility: Investigational Site Number 356026
city: Ludhiana
country: India
facility: Investigational Site Number 356032
city: Luknow
country: India
facility: Investigational Site Number 356003
city: Mangalore
country: India
facility: Investigational Site Number 356001
city: Nagpur
country: India
facility: Investigational Site Number 356030
city: New Delhi
country: India
facility: Investigational Site Number 356009
city: Pune
country: India
facility: Investigational Site Number 356023
city: Pune
country: India
facility: Investigational Site Number 356015
city: Punjgutta
country: India
facility: Investigational Site Number 356012
city: Aviano
country: Italy
facility: Investigational Site Number 380009
city: Genova
country: Italy
facility: Investigational Site Number 380001
city: Genova
country: Italy
facility: Investigational Site Number 380015
city: Milano
country: Italy
facility: Investigational Site Number 380006
city: Padova
country: Italy
facility: Investigational Site Number 380004
city: Parma
country: Italy
facility: Investigational Site Number 380008
city: Piacenza
country: Italy
facility: Investigational Site Number 380013
city: Pordenone
country: Italy
facility: Investigational Site Number 380012
city: Reggio Emilia
country: Italy
facility: Investigational Site Number 380005
city: San Donato Milanese
country: Italy
facility: Investigational Site Number 380011
city: Trieste
country: Italy
facility: Investigational Site Number 380007
city: Daegu
country: Korea, Republic of
facility: Investigational Site Number 410007
city: Goyang
country: Korea, Republic of
facility: Investigational Site Number 410006
city: Gyeonggi-do
country: Korea, Republic of
facility: Investigational Site Number 410001
city: Incheon
country: Korea, Republic of
facility: Investigational Site Number 410009
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410011
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410004
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410002
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410010
city: Seoul
country: Korea, Republic of
facility: Investigational Site Number 410008
city: Suwon
country: Korea, Republic of
facility: Investigational Site Number 410003
city: Daugavpils
country: Latvia
facility: Investigational Site Number 428004
city: Riga
country: Latvia
facility: Investigational Site Number 428003
city: Riga
country: Latvia
facility: Investigational Site Number 428002
city: Kaunas
country: Lithuania
facility: Investigational Site Number 440003
city: Kaunas
country: Lithuania
facility: Investigational Site Number 440001
city: Vilnius
country: Lithuania
facility: Investigational Site Number 440002
city: Guadalajara
country: Mexico
facility: Investigational Site Number 484001
city: Mazatlán
country: Mexico
facility: Investigational Site Number 484006
city: Christchurch
country: New Zealand
facility: Investigational Site Number 554003
city: Christchurch
country: New Zealand
facility: Investigational Site Number 554001
city: Nelson South
country: New Zealand
facility: Investigational Site Number 554002
city: Trondheim
country: Norway
facility: Investigational Site Number 578001
city: Callao
country: Peru
facility: Investigational Site Number 604003
city: Callao
country: Peru
facility: Investigational Site Number 604004
city: Lima
country: Peru
facility: Investigational Site Number 604006
city: Lima
country: Peru
facility: Investigational Site Number 604001
city: Lima
country: Peru
facility: Investigational Site Number 604005
city: Lima
country: Peru
facility: Investigational Site Number 604002
city: Bydgoszcz
country: Poland
facility: Investigational Site Number 616001
city: Bydgoszcz
country: Poland
facility: Investigational Site Number 616003
city: Gdansk
country: Poland
facility: Investigational Site Number 616006
city: Krakow
country: Poland
facility: Investigational Site Number 616005
city: Krakow
country: Poland
facility: Investigational Site Number 616018
city: Krakow
country: Poland
facility: Investigational Site Number 616020
city: Lodz
country: Poland
facility: Investigational Site Number 616009
city: Lodz
country: Poland
facility: Investigational Site Number 616002
city: Lublin
country: Poland
facility: Investigational Site Number 616010
city: Poznan
country: Poland
facility: Investigational Site Number 616012
city: Sosnowiec
country: Poland
facility: Investigational Site Number 616015
city: Szczecin
country: Poland
facility: Investigational Site Number 616013
city: Torun
country: Poland
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city: Warszawa
country: Poland
facility: Investigational Site Number 616004
city: Warszawa
country: Poland
facility: Investigational Site Number 616014
city: Wroclaw
country: Poland
facility: Investigational Site Number 616008
city: Wroclaw
country: Poland
facility: Investigational Site Number 616007
city: Wroclaw
country: Poland
facility: Investigational Site Number 616016
city: Cluj-Napoca
country: Romania
facility: Investigational Site Number 642003
city: Cluj-Napoca
country: Romania
facility: Investigational Site Number 642006
city: Cluj-Napoca
country: Romania
facility: Investigational Site Number 642005
city: Oradea
country: Romania
facility: Investigational Site Number 642001
city: Oradea
country: Romania
facility: Investigational Site Number 642004
city: Timisoara
country: Romania
facility: Investigational Site Number 642002
city: Krasnodar
country: Russian Federation
facility: Investigational Site Number 643019
city: Krasnoyarsk
country: Russian Federation
facility: Investigational Site Number 643006
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643003
city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
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city: Moscow
country: Russian Federation
facility: Investigational Site Number 643020
city: Moscow
country: Russian Federation
facility: Investigational Site Number 643021
city: Moscow
country: Russian Federation
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city: Novosibirsk
country: Russian Federation
facility: Investigational Site Number 643008
city: Novosibirsk
country: Russian Federation
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city: Omsk
country: Russian Federation
facility: Investigational Site Number 643026
city: Sestroretsk,
country: Russian Federation
facility: Investigational Site Number 643015
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 643011
city: St-Petersburg
country: Russian Federation
facility: Investigational Site Number 643018
city: St-Petersburg
country: Russian Federation
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city: St. Petersburg
country: Russian Federation
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city: St.-Petersburg
country: Russian Federation
facility: Investigational Site Number 643009
city: Tomsk
country: Russian Federation
facility: Investigational Site Number 643012
city: Vsevolozhsk
country: Russian Federation
facility: Investigational Site Number 643016
city: Yaroslavl
country: Russian Federation
facility: Investigational Site Number 643014
city: Belgrade
country: Serbia
facility: Investigational Site Number 688001
city: Belgrade
country: Serbia
facility: Investigational Site Number 688004
city: Novi Sad
country: Serbia
facility: Investigational Site Number 688002
city: Bratislava
country: Slovakia
facility: Investigational Site Number 703001
city: Celje
country: Slovenia
facility: Investigational Site Number 705001
city: Maribor
country: Slovenia
facility: Investigational Site Number 705002
city: Cape Town
country: South Africa
facility: Investigational Site Number 710001
city: Cape Town
country: South Africa
facility: Investigational Site Number 710004
city: Worcester
country: South Africa
facility: Investigational Site Number 710003
city: Barcelona
country: Spain
facility: Investigational Site Number 724001
city: Madrid
country: Spain
facility: Investigational Site Number 724002
city: Kungälv
country: Sweden
facility: Investigational Site Number 752002
city: Norrköping
country: Sweden
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city: Stockholm
country: Sweden
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city: Varberg
country: Sweden
facility: Investigational Site Number 752003
city: Istanbul
country: Turkey
facility: Investigational Site Number 792003
city: Istanbul
country: Turkey
facility: Investigational Site Number 792001
city: Istanbul
country: Turkey
facility: Investigational Site Number 792006
city: Izmir
country: Turkey
facility: Investigational Site Number 792007
city: Cherkasy
country: Ukraine
facility: Investigational Site Number 804003
city: Donetsk
country: Ukraine
facility: Investigational Site Number 804007
city: Donetsk
country: Ukraine
facility: Investigational Site Number 804010
city: Kharkiv
country: Ukraine
facility: Investigational Site Number 804011
city: Kyiv
country: Ukraine
facility: Investigational Site Number 804005
city: Kyiv
country: Ukraine
facility: Investigational Site Number 804002
city: Kyiv
country: Ukraine
facility: Investigational Site Number 804004
city: Odessa
country: Ukraine
facility: Investigational Site Number 804008
city: London
country: United Kingdom
facility: Investigational Site Number 826001
Study officials:
affiliation: Queen Mary's School of Medicine & Dentistry, London (UK)
name: Ajay Kakkar, Prof., MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: HHS-General Hospital, Hamilton, Canada
name: Alexander Turpie, MD
role: STUDY_CHAIR
References:
citation: Kakkar AK, Agnelli G, Fisher W, George D, Lassen MR, Mismetti P, Mouret P, Murphy J, Lawson F, Turpie AG; SAVE-ABDO Investigators. Preoperative enoxaparin versus postoperative semuloparin thromboprophylaxis in major abdominal surgery: a randomized controlled trial. Ann Surg. 2014 Jun;259(6):1073-9. doi: 10.1097/SLA.0000000000000430.