Evaluation of AVE5026 as Compared to Enoxaparin for the Prevention of Venous Thromboembolism in Patients Undergoing Major Abdominal Surgery (SAVE-ABDO)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00679588
First received: May 7, 2008
Last updated: November 21, 2013
Last verified: November 2013

May 7, 2008
November 21, 2013
April 2008
August 2010   (final data collection date for primary outcome measure)
Percentage of Participants Who Experience Venous Thromboembolism Event (VTE) or All-cause Death [ Time Frame: From randomization up to 10 days after surgery or the day of mandatory venography, whichever comes first ] [ Designated as safety issue: No ]

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.

Composite of any VTE and death from any cause [ Time Frame: From randomization up to the day of the event or the day of the mandatory venography; whichever comes first ]
Complete list of historical versions of study NCT00679588 on ClinicalTrials.gov Archive Site
  • Percentage of Participants Who Experience "major" VTE or All-cause Death [ Time Frame: From randomization up to 10 days after surgery or the day of mandatory venography, whichever comes first ] [ Designated as safety issue: No ]
    "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 ) [ Time Frame: From 1st study drug injection up to 3 days after last study drug injection ] [ Designated as safety issue: Yes ]

    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 [ Time Frame: From randomization up to 10 days after surgery or the day of mandatory venography, whichever comes first ] [ Designated as safety issue: No ]
    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.
  • Efficacy: Individual Components of the primary outcome measure [ Time Frame: From randomization up to the day of the event or the day of the mandatory venography; whichever comes first ]
  • Safety: Transfusions, bleeding events, laboratory data, adverse events [ Time Frame: Study period ]
  • Number of Deaths on Treatment [ Time Frame: From 1st study drug injection up to 3 days after last study drug injection ] [ Designated as safety issue: Yes ]
    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) [ Time Frame: From 1st study drug injection up to 3 days after last study drug injection ] [ Designated as safety issue: Yes ]

    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) [ Time Frame: From 1st study drug injection up to 3 days after last study drug injection ] [ Designated as safety issue: Yes ]

    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) [ Time Frame: 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 ] [ Designated as safety issue: No ]

    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.

Not Provided
 
Evaluation of AVE5026 as Compared to Enoxaparin for the Prevention of Venous Thromboembolism in Patients Undergoing Major Abdominal Surgery
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

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.

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.

Interventional
Phase 3
Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
Venous Thromboembolism
  • Drug: Semuloparin Sodium

    0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe

    Subcutaneous injection

    Other Name: AVE5026
  • Drug: Enoxaparin sodium

    0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe

    Subcutaneous injection

    Other Name: Lovenox®
  • Drug: 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

  • Experimental: Semuloparin
    Semuloparin sodium 20 mg (10 mg if Severe Renal Impairment [SRI]) once daily for 7-10 days with an initial dose given 8 hours after surgery (placebo for Enoxaparin sodium prior to surgery according to local standard for Enoxaparin and 12 hours after surgery to maintain the blind)
    Interventions:
    • Drug: Semuloparin Sodium
    • Drug: Placebo
  • Active Comparator: Enoxaparin
    Enoxaparin sodium 40 mg (20 mg if Severe Renal Impairment [SRI]) once daily for 7-10 days with an initial dose given prior to or 12 hours after surgery according to local standard for Enoxaparin sodium (placebo for Semuloparin sodium 8 hours after surgery to maintain the blind)
    Interventions:
    • Drug: Enoxaparin sodium
    • Drug: Placebo
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
4413
August 2010
August 2010   (final data collection date for primary outcome measure)

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.

Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
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
 
NCT00679588
EFC6520, 2007-007942-36
Yes
Sanofi
Sanofi
Not Provided
Principal Investigator: Ajay Kakkar, Prof., MD, PhD Queen Mary's School of Medicine & Dentistry, London (UK)
Study Chair: Alexander Turpie, MD HHS-General Hospital, Hamilton, Canada
Sanofi
November 2013

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP