Evaluation of AVE5026 as Compared to Enoxaparin for the Prevention of Thromboembolism in Patients Undergoing Total Hip Replacement Surgery (SAVE-HIP1)
- Full Text View
- Tabular View
- Study Results
- Disclaimer
- How to Read a Study Record
Purpose
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.
| 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 Elective Total Hip Replacement Surgery |
- 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.
- 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.
- 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.
| Enrollment: | 2326 |
| Study Start Date: | June 2008 |
| Study Completion Date: | June 2009 |
| Primary Completion Date: | June 2009 (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 pre-filled syringe strictly identical in appearance 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 pre-filled syringe strictly identical in appearance but without active component Subcutaneous injection |
Detailed Description:
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.
Eligibility| Ages Eligible for Study: | 18 Years and older |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
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.
Contacts and Locations
Show 30 Study Locations| 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 |
More Information
Publications:
| Responsible Party: | Sanofi |
| ClinicalTrials.gov Identifier: | NCT00697099 History of Changes |
| Other Study ID Numbers: | EFC10342, 2007-007944-80 |
| Study First Received: | June 12, 2008 |
| Last Updated: | January 14, 2013 |
| Health Authority: | United States: Food and Drug Administration |
Keywords provided by Sanofi:
|
VTE prevention Total Hip Replacement Heparin Low-Molecular-Weight |
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 May 21, 2013