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funding discontinued
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| Name | Class |
|---|---|
| LEO Pharma | INDUSTRY |
| Sunnybrook Research Institute | OTHER |
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The TILE pilot study will be a multicenter, open-label, assessor-blinded RCT (randomized control trial) comparing extended LMWH (Low Molecular Weight Heparin) vs. DOAC (Direct Oral Anticoagulants) to PTS (prevent post thrombotic syndrome) in patients with DVT (Deep Vein Thrombosis).
The TILE pilot study will investigate the magnitude of difference in effectiveness between LMWH (low molecular weight heparin, tinzaparin) plus DOAC (Direct Oral Anticoagulants, rivaroxaban) vs. DOAC alone to determine the sample size and assess feasibility for a larger study assessing the effectiveness of an initial 3-week lead-in course of LMWH (tinzaparin) compared to DOAC alone (rivaroxaban) in patients with proximal DVT (Deep Vein Thrombosis) at high risk of developing PTS (Post-Thrombotic Syndrome). PTS is a frequent, costly and burdensome complication of DVT, especially for patients with iliac or femoral vein DVT who have a high risk of developing PTS and severe PTS. Anticoagulant therapy appears to influence this risk, with a higher frequency of PTS in patients with DVT who receive suboptimal treatment with a VKA (Vitamin K Antagonist). DOAC are expected to avoid this and other limitations of VKA therapy and have become the standard of care for patients with DVT. Extended treatment of DVT with LMWH, by providing more effective anticoagulation and by reducing inflammation, appears to restore venous patency and reduce venous reflux compared to VKA and probably to DOAC. Extended treatment of DVT with LMWH, therefore, has the potential to reduce PTS.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tinzaparin | Experimental | initial 3-week lead-in course of low molecular weight heparin (tinzaparin 175 units/Kg sc daily) followed by a direct oral anticoagulant (rivaroxaban 20mg po daily) for at least 3 months |
|
| Rivaroxaban | Active Comparator | Direct oral anticoagulant only (rivaroxaban 15mg po BID for 3 weeks followed by rivaroxaban 20mg po daily ) for at least 3 months |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| tinzaparin | Drug | low molecular weight heparin |
| |
| Rivaroxaban |
| Measure | Description | Time Frame |
|---|---|---|
| PTS at 6 months | Proportion of patients with PTS at 6 months using the Villalta scale. PTS will be diagnosed using the Villalta scale. This clinical scale is the recommended standard to diagnose PTS. | 6 months post randomization |
| Main feasibility | Main feasibility outcomes: a. Proportion of eligible patients, among patients screened b. Proportion of recruited patients, among patients who are eligible c. Proportion of patients who are compliant with tinzaparin, among recruited patients assigned to tinzaparin arm. | 3 months post randomization |
| Measure | Description | Time Frame |
|---|---|---|
| PTS severity | The Villalta scale will be used to grade the severity of PTS (mild, moderate, severe) at 6 months post randomization. | 6 months post randomization |
| Villalta score at 10 days | Villalta score at 10 days |
| Measure | Description | Time Frame |
|---|---|---|
| Health Services Research Issues | QOL analyses will be conducted in the pilot study, as it is relevant to comprehensively evaluate chronic burdensome conditions like PTS. Utilities for health states will be derived from QOL measurements | 6 months post randomization |
Inclusion Criteria:
1. Patients with objectively confirmed acute (i.e. onset of symptoms <10 days) symptomatic iliac or common femoral DVT (DVT diagnosis will be made with a Compression Ultrasound (CUS) according to standardized consensus criteria)
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jean-Philippe Galanaud, MD | Sunnybrook Health Sciences Centre (Toronto, Ontario, Canada) | Principal Investigator |
| Susan R Kahn, MD | Jewish General Hospital (Montreal, Quebec, Canada) | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hamilton General Hospital | Hamilton | Ontario | L8L 2X2 | Canada | ||
| Juravinski Hospital and Cancer Centre |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32230912 | Background | Makedonov I, Kahn SR, Galanaud JP. Prevention and Management of the Post-Thrombotic Syndrome. J Clin Med. 2020 Mar 27;9(4):923. doi: 10.3390/jcm9040923. | |
| 25246013 | Background | Kahn SR, Comerota AJ, Cushman M, Evans NS, Ginsberg JS, Goldenberg NA, Gupta DK, Prandoni P, Vedantham S, Walsh ME, Weitz JI; American Heart Association Council on Peripheral Vascular Disease, Council on Clinical Cardiology, and Council on Cardiovascular and Stroke Nursing. The postthrombotic syndrome: evidence-based prevention, diagnosis, and treatment strategies: a scientific statement from the American Heart Association. Circulation. 2014 Oct 28;130(18):1636-61. doi: 10.1161/CIR.0000000000000130. Epub 2014 Sep 22. No abstract available. |
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| ID | Term |
|---|---|
| D020246 | Venous Thrombosis |
| D054070 | Postthrombotic Syndrome |
| ID | Term |
|---|---|
| D013927 | Thrombosis |
| D016769 | Embolism and Thrombosis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
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| ID | Term |
|---|---|
| D000078222 | Tinzaparin |
| D000069552 | Rivaroxaban |
| ID | Term |
|---|---|
| D006495 | Heparin, Low-Molecular-Weight |
| D006493 | Heparin |
| D006025 | Glycosaminoglycans |
| D011134 | Polysaccharides |
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Patients will be instructed not to disclose their treatment to PTS assessors
| Drug |
direct oral anticoagulant |
|
| 10 days post randomization |
| DVT-related leg pain | DVT-related leg pain will be assessed using an 11-point Likert rating scale (0 no pain, 10, worst possible pain, during the last 24 hours). This relates to sub-acute DVT pain and not a pain that could have been caused by LMWH injection | Two time points: at 10 days and at 3 months post randomization |
| Global Improvement | Assessing Patient's global improvement using the Patient's global improvement scale (On a scale of 1 to 7, where 1 is extremely improved and 7 is extremely deteriorated). | Two time points: at 10 days and at 3 months post randomization |
| Patient's satisfaction with treatment | Patient's satisfaction with treatment and patient's global improvement will be assessed using a 7-point Likert visual analog scale questionnaire (1 = extremely satisfied to 7 = extremely dissatisfied). | Two time points: at 3 weeks and at 6 months post randomization |
| QOL (Quality of Life) score - SF-36 | Generic QOL will be measured using Short-Form Health Survey-36 (SF-36) instrument. Physical and Mental Component Summary scores reflect physical and mental health status, respectively. To only take into account change in QOL related to DVT, at the 3 week visit, we will change the first sentence (i.e. stem) of the SF-36 questionnaire from 'over the past 4 weeks' to 'over the past 3 weeks'. | Three time points: at 3 weeks and at 6 months post randomization |
| QOL (Quality of Life) score - VEINES-QOL | Venous disease-specific QOL will be assessed with VEINES-QOL, a 25-item self-completed measure. To only take into account change in QOL related to DVT, at the 3 week visit, we will change the first sentence (i.e. stem) of the VEINES-QOL questionnaire from 'over the past 4 weeks' to 'over the past 3 weeks'. | Three time points: at 3 weeks and at 6 months post randomization |
| SAEs | Serious adverse events (SAE) will be defined as per the Health Canada definition. SAEs will be reported as required by local regulations, with copies sent to Health Canada, Therapeutic Product Directorate (Ottawa), Leo Pharma (maker of tinzaparin) and Bayer (maker of rivaroxaban). SAEs from baseline to 3 weeks and from 3 weeks to 6 months, including recurrent DVT, PE (Pulmonary Embolism), major bleeding and clinically relevant non-major bleeding, death will be assessed. | baseline to 6 months post randomization |
| Rate of lost to follow-up | The number of patients randomized that do not attend (in person or over the phone) the 6-month follow-up visit; Patients who withdraw consent are not considered as lost to follow-up. | 6 months post randomization |
| Hamilton |
| Ontario |
| L8V 1C3 |
| Canada |
| Sir Mortimer B. Davis Jewish General Hospital | Montréal | Ontario | H3T 1E2 | Canada |
| The Ottawa Hospital - Ottawa Hospital Research Institute (OHRI) | Ottawa | Ontario | Canada |
| Sunnybrook Health Sciences Centre | Toronto | Ontario | M4N 3M5 | Canada |
| 23615656 | Background | Hull RD, Townshend G. Long-term treatment of deep-vein thrombosis with low-molecular-weight heparin: an update of the evidence. Thromb Haemost. 2013 Jul;110(1):14-22. doi: 10.1160/TH12-12-0931. Epub 2013 Apr 25. |
| 19175497 | Background | Kahn SR, Partsch H, Vedantham S, Prandoni P, Kearon C; Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of post-thrombotic syndrome of the leg for use in clinical investigations: a recommendation for standardization. J Thromb Haemost. 2009 May;7(5):879-83. doi: 10.1111/j.1538-7836.2009.03294.x. Epub 2009 Jan 19. |
| 37907305 | Derived | Makedonov I, Kahn S, Abdulrehman J, Schulman S, Delluc A, Gross PL, Galanaud JP. TILE pilot trial study protocol: Tinzaparin Lead-in to Prevent the Post-Thrombotic syndrome study protocol. BMJ Open. 2023 Oct 31;13(10):e064715. doi: 10.1136/bmjopen-2022-064715. |
| D014689 |
| Venous Insufficiency |
| D002241 |
| Carbohydrates |
| D013876 | Thiophenes |
| D013457 | Sulfur Compounds |
| D009930 | Organic Chemicals |
| D009025 | Morpholines |
| D010078 | Oxazines |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |