Venous ThromboembolismPhase 2TREKNCT00331838
Prevention of Venous Thromboembolism in Patients Undergoing Elective Total Knee Replacement Surgery
A Phase 2 study testing Semuloparin sodium and Enoxaparin sodium in people with Venous Thromboembolism, run by Sanofi at 19 sites in 19 countries.
Trial summary
The primary objective was to demonstrate the dose-response of Semuloparin sodium (AVE5026) for the prevention of Venous Thromboembolism [VTE] in patients undergoing total knee replacement [TKR] 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?
- Semuloparin sodium and Enoxaparin sodium
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 705 participants
- Where
- 19 sitesin 19 countries
- Study dates
- May 2006to Jun 2007
- Phase
- Phase 2
- 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
- Patient scheduled to undergo elective total knee replacement or revision of a primary procedure performed ≥ 6 months prior to study entry.
Who cannot join
- Any major orthopedic surgery in the 3 months prior to study entry;
- Clinical signs or symptoms of DVT or PE within the last 12 months or known post-phlebitic syndrome;
- Known sensitivity to iodine or contrast dyes;
- Recent stroke or myocardial infarction;
- High risk of bleeding;
- Treatment with other anti-thrombotic agents within 7 days prior to surgery;
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- Any contra-indication to Unfractionated Heparin or Low Molecular Weight Heparin;
- Pregnant or nursing woman, or woman of childbearing potential who is not using an effective contraceptive method.
- 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
19 sites in 19 countries.
19 sites in 19 countries
About this study
Official title: A Multicenter, Randomized, Double-Blind, Double-Dummy, Parallel Group, Dose Response Study of Subcutaneous AVE5026 With an Enoxaparin Calibrator Arm in the Prevention of Venous Thromboembolism in Patients Undergoing Elective Total Knee Replacement Surgery
The primary objective was to demonstrate the dose-response of Semuloparin sodium (AVE5026) for the prevention of Venous Thromboembolism [VTE] in patients undergoing total knee replacement [TKR] surgery.
Secondary objectives were to evaluate the safety (incidence of major bleeding) of AVE5026, to document the efficacy and safety of AVE5026 post-operative regimens, and to assess the pharmacokinetic parameters of AVE5026.
Read the detailed description
The randomization had to take place before the first study drug injection.
The total duration of observation per participant was 27-33 days from surgery broken down as follows:
- 4 to 10-day double-blind treatment period;
- Follow-up period up to Day 30 ± 3 after surgery.
Mandatory bilateral venography of the lower limbs had to be performed between 5 to 11 days after surgery.
- Conditions
- Venous Thromboembolism
- Being tested
- Semuloparin sodium, Placebo (for Enoxaparin sodium), Enoxaparin sodium, Placebo (for Semuloparin sodium)
- Keywords
- Prevention, Venous Thrombosis, Orthopedic Surgery
- Medical subject headings
- Venous Thromboembolism, Venous Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Semuloparin sodiumDrug
Also called AVE5026
0.8 mL solution in Type I amber glass vials
Subcutaneous injection
Placebo (for Enoxaparin sodium)Drug
0.4 mL solution in ready-to-use prefilled syringe strictly identical in appearance containing the same volume but without active component
Subcutaneous injection
Enoxaparin sodiumDrug
Also called Lovenox®
0.4 mL solution in ready-to-use pre-filled syringe
Subcutaneous injection
Placebo (for Semuloparin sodium)Drug
0.8 ml solution in type I amber glass vials strictly identical in appearance containing the same volume but without active component
Subcutaneous injection
| Study group | Role | What they receive |
|---|---|---|
| Semuloparin 5 mg | Experimental | Semuloparin sodium 5 mg + Placebo (for Enoxaparin sodium) once daily for 4-10 days with an initial dose given 12 hours before or 8 hours after surgery depending on the willingness of the investigator Receives: Drug: Semuloparin sodium; Drug: Placebo (for Enoxaparin sodium) |
| Semuloparin 10 mg | Experimental | Semuloparin sodium 10 mg + Placebo (for Enoxaparin sodium) once daily for 4-10 days with an initial dose given 12 hours before or 8 hours after surgery depending on the willingness of the investigator Receives: Drug: Semuloparin sodium; Drug: Placebo (for Enoxaparin sodium) |
| Semuloparin 20 mg | Experimental | Semuloparin sodium 20 mg + Placebo (for Enoxaparin sodium) once daily for 4-10 days with an initial dose given 12 hours before or 8 hours after surgery depending on the willingness of the investigator Receives: Drug: Semuloparin sodium; Drug: Placebo (for Enoxaparin sodium) |
| Semuloparin 40 mg | Experimental | Semuloparin sodium 40 mg + Placebo (for Enoxaparin sodium) once daily for 4-10 days with an initial dose given 12 hours before or 8 hours after surgery depending on the willingness of the investigator Receives: Drug: Semuloparin sodium; Drug: Placebo (for Enoxaparin sodium) |
| Semuloparin 60 mg | Experimental | Semuloparin sodium 60 mg + Placebo (for Enoxaparin sodium) once daily for 4-10 days with an initial dose given 12 hours before or 8 hours after surgery depending on the willingness of the investigator Receives: Drug: Semuloparin sodium; Drug: Placebo (for Enoxaparin sodium) |
| Enoxaparin 40 mg | Active comparator | Enoxaparin sodium 40 mg + Placebo (for Semuloparin sodium) once daily for 4-10 days with an initial dose given 12 hours before or 8 hours after surgery depending on the willingness of the investigator Receives: Drug: Enoxaparin sodium; Drug: Placebo (for Semuloparin sodium) |
| Placebo pre-op / Semuloparin 20 mg | Experimental | Placebo (for Semuloparin sodium) + Placebo (for Enoxaparin sodium) 12 hours before surgery then,
Semuloparin sodium 20 mg + Placebo (for Enoxaparin sodium) once daily for 4-10 days with an initial dose given 8 hours after surgery Receives: Drug: Semuloparin sodium; Drug: Placebo (for Enoxaparin sodium); Drug: Placebo (for Semuloparin sodium) |
| Placebo pre-op / Semuloparin 40 mg | Experimental | Placebo (for Semuloparin sodium) + Placebo (for Enoxaparin sodium) 12 hours before surgery then,
Semuloparin sodium 40 mg + Placebo (for Enoxaparin sodium) once daily for 4-10 days with an initial dose given 8 hours after surgery Receives: Drug: Semuloparin sodium; Drug: Placebo (for Enoxaparin sodium); Drug: Placebo (for Semuloparin sodium) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants Who Experienced Venous Thromboembolism Event (VTE) or VTE-related Death
VTE included any Deep Vein Thrombosis [DVT] identified on mandatory venography of the lower limbs; symptomatic DVT and/or non-fatal pulmonary embolism [PE] before mandatory examination; VTE related deaths included fatal PE or deaths which could not be attributed to a documented cause and for which PE could not be ruled out. All events were to be confirmed by a Central Independent Adjudication Committee [CIAC] based on venographies, scheduled or unscheduled, and other available diagnostic tests (ultrasonography, ventilation/perfusion lung scan, pulmonary angiography, autopsy report, etc).
Measured: From surgery to Day 11 or the day of mandatory venography, whichever came first
Secondary outcomes (4)
Number of Participants Who Experienced DVT
Measured: From surgery up to Day 11 or the day of mandatory venography, whichever came first
Number of Participants Who Experienced Symptomatic VTE
Symptomatic VTE included:
- suspected DVT confirmed by the CIAC based on compression ultrasonography or venography;
- suspected PE confirmed by the CIAC based on perfusion/ventilation lung scan, pulmonary angiography or spiral computerized tomography.
Measured: From surgery up to Day 11 or the day of mandatory venography, whichever came first
Number of Participants Who Experienced Bleedings
Bleedings were centrally and blindly reviewed by the CIAC and classified as:
- "Major" (fatal bleeding, bleeding that was retroperitoneal or intracranial or that involved any other critical organ (e.g. eye, adrenal gland, pericardium or spine), surgical site bleeding leading to intervention, non-surgical site bleeding requiring surgical intervention or with a bleeding index ≥2);
- "Minor" (overt bleeding considered more than expected but not meeting the criteria for major bleeding);
- "Criteria for bleeding event not satisfied" (not meeting the criteria for major or minor bleeding).
Measured: From 1st study drug injection up to 3 days after last study drug injection (median duration of approximately 11 days)
Number of Participants Who Required 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 answers to questions asked after diagnostic tests for suspected VTE and/or the mandatory venography.
Measured: From surgery up to Day 11 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 posted31 May 2006 (estimated)
- Study startMay 2006
- Primary completionJun 2007
- Study completionJun 2007
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 2
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 705 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sanofi
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Michael LASSEN, MD, Study chair, Hoersholm Hospital (Denmark)
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00331838
- Sponsor's protocol ID
- DRI6243
- Other IDs
- 2005-006202-26, 2005
- Acronym
- TREK
- Status last verified
- Jan 2013
- First submitted
- 18 May 2006
- Last updated
- 15 Jan 2013
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Lassen MR, Dahl OE, Mismetti P, Destree D, Turpie AG. AVE5026, a new hemisynthetic ultra-low-molecular-weight heparin for the prevention of venous thromboembolism in patients after total knee replacement surgery--TREK: a dose-ranging study. J Thromb Haemost. 2009 Apr;7(4):566-72. doi: 10.1111/j.1538-7836.2009.03301.x. Epub 2009 Jan 24.
PubMed 19187076
Study at a glance
From the registry record, last updated by the sponsor on 15 Jan 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Randomized, Double-Blind, Double-Dummy, Parallel Group, Dose Response Study of Subcutaneous AVE5026 With an Enoxaparin Calibrator Arm in the Prevention of Venous Thromboembolism in Patients Undergoing Elective Total Knee Replacement Surgery
- ClinicalTrials.gov ID
- NCT00331838
- Acronym / sponsor ID
- TREK / DRI6243
- Conditions
- Venous Thromboembolism
- Keywords
- Prevention, Venous Thrombosis, Orthopedic Surgery
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 705 participants (actual)
- Lead sponsor
- SanofiIndustry (pharma, biotech, devices)
- Study start
- May 2006
- Primary completion
- Jun 2007 (actual)
- Study completion
- Jun 2007 (actual)
- First posted
- 31 May 2006 (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 demonstrate the dose-response of Semuloparin sodium (AVE5026) for the prevention of Venous Thromboembolism [VTE] in patients undergoing total knee replacement [TKR] surgery.
Secondary objectives were to evaluate the safety (incidence of major bleeding) of AVE5026, to document the efficacy and safety of AVE5026 post-operative regimens, and to assess the pharmacokinetic parameters of AVE5026.
Detailed description
The randomization had to take place before the first study drug injection.
The total duration of observation per participant was 27-33 days from surgery broken down as follows:
- 4 to 10-day double-blind treatment period;
- Follow-up period up to Day 30 ± 3 after surgery.
Mandatory bilateral venography of the lower limbs had to be performed between 5 to 11 days after surgery.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 8
| Arm | Type | Receives |
|---|---|---|
| Semuloparin 5 mg | Experimental | Drug: Semuloparin sodium, Drug: Placebo (for Enoxaparin sodium)Semuloparin sodium 5 mg + Placebo (for Enoxaparin sodium) once daily for 4-10 days with an initial dose given 12 hours before or 8 hours after surgery depending on the willingness of the investigator |
| Semuloparin 10 mg | Experimental | Drug: Semuloparin sodium, Drug: Placebo (for Enoxaparin sodium)Semuloparin sodium 10 mg + Placebo (for Enoxaparin sodium) once daily for 4-10 days with an initial dose given 12 hours before or 8 hours after surgery depending on the willingness of the investigator |
| Semuloparin 20 mg | Experimental | Drug: Semuloparin sodium, Drug: Placebo (for Enoxaparin sodium)Semuloparin sodium 20 mg + Placebo (for Enoxaparin sodium) once daily for 4-10 days with an initial dose given 12 hours before or 8 hours after surgery depending on the willingness of the investigator |
| Semuloparin 40 mg | Experimental | Drug: Semuloparin sodium, Drug: Placebo (for Enoxaparin sodium)Semuloparin sodium 40 mg + Placebo (for Enoxaparin sodium) once daily for 4-10 days with an initial dose given 12 hours before or 8 hours after surgery depending on the willingness of the investigator |
| Semuloparin 60 mg | Experimental | Drug: Semuloparin sodium, Drug: Placebo (for Enoxaparin sodium)Semuloparin sodium 60 mg + Placebo (for Enoxaparin sodium) once daily for 4-10 days with an initial dose given 12 hours before or 8 hours after surgery depending on the willingness of the investigator |
| Enoxaparin 40 mg | Active comparator | Drug: Enoxaparin sodium, Drug: Placebo (for Semuloparin sodium)Enoxaparin sodium 40 mg + Placebo (for Semuloparin sodium) once daily for 4-10 days with an initial dose given 12 hours before or 8 hours after surgery depending on the willingness of the investigator |
| Placebo pre-op / Semuloparin 20 mg | Experimental | Drug: Semuloparin sodium, Drug: Placebo (for Enoxaparin sodium), Drug: Placebo (for Semuloparin sodium)Placebo (for Semuloparin sodium) + Placebo (for Enoxaparin sodium) 12 hours before surgery then, Semuloparin sodium 20 mg + Placebo (for Enoxaparin sodium) once daily for 4-10 days with an initial dose given 8 hours after surgery |
| Placebo pre-op / Semuloparin 40 mg | Experimental | Drug: Semuloparin sodium, Drug: Placebo (for Enoxaparin sodium), Drug: Placebo (for Semuloparin sodium)Placebo (for Semuloparin sodium) + Placebo (for Enoxaparin sodium) 12 hours before surgery then, Semuloparin sodium 40 mg + Placebo (for Enoxaparin sodium) once daily for 4-10 days with an initial dose given 8 hours after surgery |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Patient scheduled to undergo elective total knee replacement or revision of a primary procedure performed ≥ 6 months prior to study entry.
Key exclusion criteria (9 listed)
- Any major orthopedic surgery in the 3 months prior to study entry;
- Clinical signs or symptoms of DVT or PE within the last 12 months or known post-phlebitic syndrome;
- Known sensitivity to iodine or contrast dyes;
- Recent stroke or myocardial infarction;
- 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 |
|---|---|---|
| Semuloparin sodiumAlso: AVE50260.8 mL solution in Type I amber glass vials Subcutaneous injection | Drug | Placebo pre-op / Semuloparin 20 mg, Placebo pre-op / Semuloparin 40 mg, Semuloparin 10 mg, Semuloparin 20 mg, Semuloparin 40 mg, Semuloparin 5 mg, Semuloparin 60 mg |
| Placebo (for Enoxaparin sodium)0.4 mL solution in ready-to-use prefilled syringe strictly identical in appearance containing the same volume but without active component Subcutaneous injection | Drug | Placebo pre-op / Semuloparin 20 mg, Placebo pre-op / Semuloparin 40 mg, Semuloparin 10 mg, Semuloparin 20 mg, Semuloparin 40 mg, Semuloparin 5 mg, Semuloparin 60 mg |
| Enoxaparin sodiumAlso: Lovenox®0.4 mL solution in ready-to-use pre-filled syringe Subcutaneous injection | Drug | Enoxaparin 40 mg |
| Placebo (for Semuloparin sodium)0.8 ml solution in type I amber glass vials strictly identical in appearance containing the same volume but without active component Subcutaneous injection | Drug | Enoxaparin 40 mg, Placebo pre-op / Semuloparin 20 mg, Placebo pre-op / Semuloparin 40 mg |
Primary outcome
Number of Participants Who Experienced Venous Thromboembolism Event (VTE) or VTE-related Death
Time frame: From surgery to Day 11 or the day of mandatory venography, whichever came first
VTE included any Deep Vein Thrombosis [DVT] identified on mandatory venography of the lower limbs; symptomatic DVT and/or non-fatal pulmonary embolism [PE] before mandatory examination; VTE related deaths included fatal PE or deaths which could not be attributed to a documented cause and for which PE could not be ruled out. All events were to be confirmed by a Central Independent Adjudication Committee [CIAC] based on venographies, scheduled or unscheduled, and other available diagnostic tests (ultrasonography, ventilation/perfusion lung scan, pulmonary angiography, autopsy report, etc).
4 secondary outcomes
Number of Participants Who Experienced DVT
Time frame: From surgery up to Day 11 or the day of mandatory venography, whichever came first
Number of Participants Who Experienced Symptomatic VTE
Time frame: From surgery up to Day 11 or the day of mandatory venography, whichever came first
Number of Participants Who Experienced Bleedings
Time frame: From 1st study drug injection up to 3 days after last study drug injection (median duration of approximately 11 days)
Number of Participants Who Required Initiation of Curative Anticoagulant or Thrombolytic Treatment After VTE Assessment
Time frame: From surgery up to Day 11 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 15 Jan 2013.
- Results publication: PubMed 19187076Lassen MR, Dahl OE, Mismetti P, Destree D, Turpie AG. AVE5026, a new hemisynthetic ultra-low-molecular-weight heparin for the prevention of venous thromboembolism in patients after total knee replacement surgery--TREK: a dose-ranging study. J Thromb Haemost. 2009 Apr;7(4):566-72. doi: 10.1111/j.1538-7836.2009.03301.x. Epub 2009 Jan 24.
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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.
Michael LASSEN, MD study chair
Hoersholm Hospital (Denmark)
19 sites in 19 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Semuloparin sodium and Enoxaparin sodium in people with Venous Thromboembolism, run by Sanofi at 19 sites in 19 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 9 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 15 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 19 sites in Argentina, Bulgaria, Chile, Colombia, Denmark and 14 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
Number of Participants Who Experienced Venous Thromboembolism Event (VTE) or VTE-related Death (time frame: From surgery to Day 11 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 NCT00331838, 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 15 Jan 2013.