Venous ThromboembolismPhase 3SAVE-HIP2NCT00721760
Evaluation of AVE5026 as Compared to Enoxaparin for the Prevention of Thromboembolism in Patients Undergoing Hip Fracture Surgery
A Phase 3 study testing Enoxaparin sodium and Semuloparin sodium in people with Venous Thromboembolism, run by Sanofi at 25 sites in 25 countries.
Trial summary
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 hip fracture surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Venous Thromboembolism
- What is being tested?
- Enoxaparin sodium and Semuloparin sodium
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1,003 participants
- Where
- 25 sitesin 25 countries
- Study dates
- Jul 2008to Oct 2009
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Standard surgery for fracture of the upper third of the femur including femoral head and neck.
Who cannot join
- Estimated time of injury/fracture > 24 hours before admission to hospital;
- Any major orthopedic surgery in the 3 months prior to study start;
- Multiple trauma affecting more than one organ system;
- 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, or pork products;
- 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.
Trial locations and contacts
25 sites in 25 countries.
25 sites in 25 countries
United States1 site
Sanofi-Aventis Administrative Office
Bridgewater, New Jersey, 08807
About this study
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 Hip Fracture 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 hip fracture surgery.
The secondary objectives were to evaluate the safety of AVE5026 in patients undergoing hip fracture surgery, and to document AVE5026 exposure in this population.
Read the detailed description
Randomization had to take place just prior to 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 between 7 to 11 days after surgery.
- Conditions
- Venous Thromboembolism
- Being tested
- Enoxaparin sodium, Semuloparin sodium, Placebo
- Keywords
- Hip fractures, Heparin Low-Molecular-Weight, Randomized Controlled Trial
- Medical subject headings
- Venous Thromboembolism, Hip Fractures
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Enoxaparin sodiumDrug
Also called Lovenox®
0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe
Subcutaneous injection
Semuloparin sodiumDrug
Also called AVE5026
0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe
Subcutaneous injection
PlaceboDrug
0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml prefilled syringe strictly identical in appearance but without active component
Subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Semuloparin | Experimental | 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 Receives: Drug: Semuloparin sodium; Drug: Placebo |
| Enoxaparin | Active comparator | 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 Receives: Drug: Enoxaparin sodium; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percentage of Participants Who Experienced Venous Thromboembolism Event [VTE] or All-cause Death
VTE included any Deep Vein Thrombosis [DVT] (proximal or distal, 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.
Measured: From randomization up to 10 days after surgery or the day of mandatory venography, whichever came first
Secondary outcomes (3)
Percentage of Participants Who Experienced "Major" VTE or All-cause Death
"major" VTE included any proximal DVT, symptomatic distal DVT and non-fatal PE as confirmed by the CIAC.
Measured: From randomization up to 10 days after surgery or the day of mandatory venography, whichever came first
Percentage of Participants Who Experienced Clinically Relevant Bleedings
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".
Measured: From first study drug injection up to 3 days after last study drug injection
Percentage of Participants Who Required the Initiation of Curative Anticoagulant or Thrombolytic Treatment After VTE Assessment
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.
Measured: From randomization up to 10 days after surgery or the day of mandatory venography, whichever came first
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2008 (estimated)
- Study startJul 2008
- Primary completionOct 2009
- Study completionOct 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Venous ThromboembolismStudies of the same condition, open and under way.
- More trials run by SanofiThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1,003 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- William D. Fisher, MD, Principal investigator, Department of Orthopaedic Surgery, McGill University Health Centre, 1650 Cedar Avenue, Montreal, Quebec, H3G 1A4, CanadaAlexander G. Turpie, Study chair, McMaster University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00721760
- Sponsor's protocol ID
- EFC10343
- Other IDs
- 2007-007945-11
- Acronym
- SAVE-HIP2
- Status last verified
- Jan 2013
- First submitted
- 22 Jul 2008
- Last updated
- 23 Jan 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 22429800
Study at a glance
From the registry record, last updated by the sponsor on 23 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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 Hip Fracture Surgery
- ClinicalTrials.gov ID
- NCT00721760
- Acronym / sponsor ID
- SAVE-HIP2 / EFC10343
- Conditions
- Venous Thromboembolism
- Keywords
- Hip fractures, Heparin Low-Molecular-Weight, Randomized Controlled Trial
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 1,003 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- Jul 2008
- Primary completion
- Oct 2009 (actual)
- Study completion
- Oct 2009 (actual)
- First posted
- 24 Jul 2008 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 hip fracture surgery.
The secondary objectives were to evaluate the safety of AVE5026 in patients undergoing hip fracture surgery, and to document AVE5026 exposure in this population.
Detailed description
Randomization had to take place just prior to 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 between 7 to 11 days after surgery.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Semuloparin | Experimental | Drug: Semuloparin sodium, Drug: PlaceboSemuloparin 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 |
| Enoxaparin | Active comparator | Drug: Enoxaparin sodium, Drug: PlaceboEnoxaparin 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Standard surgery for fracture of the upper third of the femur including femoral head and neck.
Key exclusion criteria (8 listed)
- Estimated time of injury/fracture > 24 hours before admission to hospital;
- Any major orthopedic surgery in the 3 months prior to study start;
- Multiple trauma affecting more than one organ system;
- Deep vein thrombosis or pulmonary embolism within the last 12 months or known post-phlebitic syndrome;
- High risk of bleeding;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Enoxaparin sodiumAlso: Lovenox®0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe Subcutaneous injection | Drug | Enoxaparin |
| Semuloparin sodiumAlso: AVE50260.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml pre-filled syringe Subcutaneous injection | Drug | Semuloparin |
| Placebo0.4 mL (0.2 mL if SRI) solution in ready-to-use 0.5 ml prefilled syringe strictly identical in appearance but without active component Subcutaneous injection | Drug | Enoxaparin, Semuloparin |
Primary outcome
Percentage of Participants Who Experienced 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 came first
VTE included any Deep Vein Thrombosis [DVT] (proximal or distal, 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.
3 secondary outcomes
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
Percentage of Participants Who Experienced Clinically Relevant Bleedings
Time frame: From first study drug injection up to 3 days after last study drug injection
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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 Jan 2013.
- Results publication: PubMed 22429800Lassen 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
William D. Fisher, MD principal investigator
Department of Orthopaedic Surgery, McGill University Health Centre, 1650 Cedar Avenue, Montreal, Quebec, H3G 1A4, Canada
Alexander G. Turpie study chair
McMaster University
25 sites in 25 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Enoxaparin sodium and Semuloparin sodium in people with Venous Thromboembolism, run by Sanofi at 25 sites in 25 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 23 Jan 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 25 sites in United States, Argentina, Belarus, Bulgaria, Canada and 20 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percentage of Participants Who Experienced 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 came first). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00721760, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 Jan 2013.