Evaluation of AVE5026 as Compared to Enoxaparin for the Prevention of Thromboembolism in Patients Undergoing Total Hip Replacement Surgery (SAVE-HIP1)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Sanofi
ClinicalTrials.gov Identifier:
NCT00697099
First received: June 12, 2008
Last updated: January 14, 2013
Last verified: January 2013

June 12, 2008
January 14, 2013
June 2008
June 2009   (final data collection date for primary outcome measure)
Percentage of Participants Who Experienced Venous Thromboembolism Event [VTE] or Death From Any Cause [ Time Frame: From randomization up to 10 days after surgery or the day of mandatory venography, whichever came first ] [ Designated as safety issue: No ]

VTE included 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 included fatal PE and deaths for other reason than PE.

Composite of any VTE and deaths from any cause [ Time Frame: From randomization up to the day of an event or the day of mandatory venography, whichever comes first ] [ Designated as safety issue: No ]
Complete list of historical versions of study NCT00697099 on ClinicalTrials.gov Archive Site
  • Percentage of Participants Who Experienced "Major" VTE or All-cause Death [ Time Frame: From randomization up to 10 days after surgery or the day of mandatory venography, whichever came first ] [ Designated as safety issue: No ]
    "major" VTE included any proximal DVT, symptomatic distal DVT and nonfatal Pulmonary Embolism (PE) as confirmed by the CIAC.
  • Percentage of Participants Who Experienced Clinically Relevant Bleedings [ Time Frame: From first study drug injection up to 3 days after last study drug injection ] [ Designated as safety issue: Yes ]

    Bleedings were 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 healthcare professional);
    • "Non-clinically relevant bleeding".
  • Percentage of Participants Who Required 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 came 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.
  • Composite of proximal deep vein thrombosis, symptomatic distal deep vein thrombosis, non fatal pulmonary embolism, all cause deaths [ Time Frame: From randomization up to the day of an event or the day of mandatory venography, whichever comes first ] [ Designated as safety issue: No ]
  • Safety: Bleeding, transfusions,laboratory data, adverse events, deaths [ Time Frame: Study period ] [ Designated as safety issue: Yes ]
  • Overview of deaths [ Time Frame: From first study drug injection up to 3 days after last study drug injection ] [ Designated as safety issue: Yes ]
    All deaths were 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 first study drug injection up to 3 days after last study drug injection ] [ Designated as safety issue: Yes ]

    PCSA values are abnormal values considered medically important by the Sponsor according to predefined criteria based on literature review.

    Threshold for platelet counts was defined as <100 Giga/L.

  • Liver Function: Percentage of Participants With Potentially Clinically Significant Abnormalities [PCSA] [ Time Frame: From first study drug injection up to 3 days after last study drug injection ] [ Designated as safety issue: Yes ]

    Thresholds were defined as follows:

    • Alanine Aminotransferase [ALAT] >3 Upper Normal Limit [ULN];
    • Total Bilirubin [TB] >2 ULN;
    • ALAT >3 ULN and TB >2 ULN;

    Cases with ALAT >3 ULN and TB >2 ULN (not necessarily concomitant) were evaluated by a blinded independent adjudicator to determine if they met Hy's law criteria.

Not Provided
 
Evaluation of AVE5026 as Compared to Enoxaparin for the Prevention of Thromboembolism in Patients Undergoing Total Hip Replacement 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 Elective Total Hip Replacement Surgery

The primary objective was to compare the efficacy 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 elective total hip replacement surgery.

The secondary objectives were to evaluate the safety of AVE5026 in patients undergoing elective total hip replacement surgery, and to document AVE5026 exposure in this population.

Randomization had to take place just prior the first study drug injection (randomization ratio 1:1).

The total duration of observation per participant was 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 had to be performed 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 pre-filled syringe strictly identical in appearance 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
Lassen MR, Fisher W, Mouret P, Agnelli G, George D, Kakkar A, Mismetti P, Turpie AG; SAVE Investigators. Semuloparin for prevention of venous thromboembolism after major orthopedic surgery: results from three randomized clinical trials, SAVE-HIP1, SAVE-HIP2 and SAVE-KNEE. J Thromb Haemost. 2012 May;10(5):822-32. doi: 10.1111/j.1538-7836.2012.04701.x.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
2326
June 2009
June 2009   (final data collection date for primary outcome measure)

Inclusion Criteria:

  • Elective total hip replacement surgery or a revision of at least one component of a prosthesis implanted ≥ 6 months prior to study entry.

Exclusion Criteria:

  • Any major orthopedic surgery in the 3 months prior to study start;
  • Deep vein thrombosis or pulmonary embolism within the last 12 months or known post-phlebitic syndrome;
  • High risk of bleeding;
  • Known allergy to heparin or enoxaparin;
  • Any contra-indications to the performance of venography;
  • End stage renal disease or patient on dialysis.

The above information is 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,   Belarus,   Canada,   Chile,   Colombia,   Czech Republic,   Denmark,   Estonia,   Finland,   Germany,   Greece,   India,   Italy,   Mexico,   Norway,   Peru,   Philippines,   Poland,   Romania,   Russian Federation,   Slovakia,   South Africa,   Spain,   Sweden,   Taiwan,   Thailand,   Turkey,   Ukraine
 
NCT00697099
EFC10342, 2007-007944-80
Yes
Sanofi
Sanofi
Not Provided
Principal Investigator: Patrick MOURET, MD Orthopädische Klinik, Stätische Klinik, Gotenstrasse 6-8, Frankfurt Höechst, 65929 Frankfurt, Germany
Study Chair: Alexander G. TURPIE, MD HHS-General Hospital, Hamilton, Ontario, Canada
Sanofi
January 2013

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