Venous Thromboembolism
Conditions
Keywords
Digestive System Surgical Procedure, Urologic Surgical Procedure, Prevention of venous thromboembolism, Abdominal surgery
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.
Interventions
0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe Subcutaneous injection
DRUGEnoxaparin sodium
0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe Subcutaneous injection
DRUGPlacebo
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
Sponsors
Sanofi
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experience Venous Thromboembolism Event (VTE) or All-cause Death | From randomization up to 10 days after surgery or the day of mandatory venography, whichever comes first | 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. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants Who Experience major VTE or All-cause Death | From randomization up to 10 days after surgery or the day of mandatory venography, whichever comes first | major VTE includes any proximal DVT, symptomatic distal DVT and non-fatal Pulmonary Embolism (PE) as as confirmed by the CIAC. |
| Percentage of Participants Who Experience Clinically Relevant Bleedings (major and clinically relevant non-major bleedings ) | From 1st study drug injection up to 3 days after last study drug injection | 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. |
| Percentage of Participants requiring the initiation of curative anticoagulant or thrombolytic treatment after VTE assessment | From randomization up to 10 days after surgery or the day of mandatory venography, whichever comes first | 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Number of Deaths on Treatment | From 1st study drug injection up to 3 days after last study drug injection | 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). |
| Platelets Count: Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA) | From 1st study drug injection up to 3 days after last study drug injection | 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. |
| Liver Function: Percentage of Participants With Potentially Clinically Significant Abnormalities (PCSA) | From 1st study drug injection up to 3 days after last study drug injection | 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. |
| Trough Plasma Concentration of Semuloparin Sodium (AVE5026) | 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 | 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. |
Countries
Argentina, Australia, Austria, Belarus, Belgium, Brazil, Bulgaria, Canada, Chile, China, Croatia, Czechia, Denmark, Estonia, Germany, Greece, Hungary, India, Italy, Latvia, Lithuania, Mexico, New Zealand, Norway, Peru, Poland, Romania, Russia, Serbia, Slovakia, Slovenia, South Africa, South Korea, Spain, Sweden, Turkey (Türkiye), Ukraine, United Kingdom, United States
Outcome results
None listed