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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
9
low molecular weight heparin
direct oral anticoagulant
Hamilton General Hospital
Hamilton, Ontario, Canada
Juravinski Hospital and Cancer Centre
Hamilton, Ontario, Canada
Sir Mortimer B. Davis Jewish General Hospital
Montréal, Ontario, Canada
The Ottawa Hospital - Ottawa Hospital Research Institute (OHRI)
Ottawa, Ontario, Canada
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.
Time frame: 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.
Time frame: 3 months post randomization
PTS severity
The Villalta scale will be used to grade the severity of PTS (mild, moderate, severe) at 6 months post randomization.
Time frame: 6 months post randomization
Villalta score at 10 days
Villalta score at 10 days
Time frame: 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
Time frame: 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).
Time frame: Two time points: at 10 days and at 3 months post randomization
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Sunnybrook Health Sciences Centre
Toronto, Ontario, Canada
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).
Time frame: 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'.
Time frame: 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'.
Time frame: 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.
Time frame: 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.
Time frame: 6 months post randomization