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
  Purpose

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.


Condition Intervention Phase
Venous Thromboembolism
Drug: Semuloparin Sodium
Drug: Enoxaparin sodium
Drug: Placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Sanofi:

Primary Outcome Measures:
  • 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.



Secondary Outcome Measures:
  • 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.


Other Outcome Measures:
  • 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.



Enrollment: 4413
Study Start Date: April 2008
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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)
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: 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

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)
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


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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.

  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00679588

  Show 270 Study Locations
Sponsors and Collaborators
Sanofi
Investigators
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
  More Information

No publications provided by Sanofi

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Sanofi
ClinicalTrials.gov Identifier: NCT00679588     History of Changes
Other Study ID Numbers: EFC6520, 2007-007942-36
Study First Received: May 7, 2008
Last Updated: November 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Sanofi:
Digestive System Surgical Procedure
Urologic Surgical Procedure
Prevention of venous thromboembolism
Abdominal surgery

Additional relevant MeSH terms:
Thromboembolism
Venous Thromboembolism
Venous Thrombosis
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Thrombosis
Enoxaparin
Anticoagulants
Hematologic Agents
Therapeutic Uses
Pharmacologic Actions
Fibrinolytic Agents
Fibrin Modulating Agents
Molecular Mechanisms of Pharmacological Action
Cardiovascular Agents

ClinicalTrials.gov processed this record on August 28, 2014