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Deep Vein ThrombosisPhase 4TILENCT04794569

Tinzaparin Lead-In to Prevent the Post-Thrombotic Syndrome

A Phase 4 study testing tinzaparin and Rivaroxaban in people with Deep Vein Thrombosis and Post Thrombotic Syndrome, run by Sunnybrook Health Sciences Centre at 5 sites in Canada.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

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). Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
tinzaparin and Rivaroxaban
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
5 sitesCanada
Study dates
15 Nov 2021to 19 Jan 2024
Phase
Phase 4
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

  • 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)

Who cannot join

  • Age < 18 years
  • History of ipsilateral DVT (distal and/or proximal)
  • Active cancer
  • Thrombolysis or other invasive early thrombus removal technique to treat DVT or PE
  • Pregnant or breast feeding
  • Impaired renal function (creatinine clearance < 30 ml/min according to Cockcroft-Gault formula)
Show all 20Show fewer
  • Concomitant use of drugs that interact with rivaroxaban (i.e. keto- or itraconazole, ritonavir)
  • Allergy or hypersensitivity to heparin or rivaroxaban, including heparin induced thrombocytopenia
  • Anticoagulant therapy contraindicated because of presence of active bleeding or condition with high risk of bleeding (e.g. peptic ulcer, acute or subacute septic endocarditis, uncontrolled severe hypertension, other)
  • Thrombocytopenia (platelet count < 100 x 109/L)
  • Liver disease (including Child-Pugh Class B and Class C) associated with coagulopathy
  • Body weight > 120 kg or < 40 kg
  • Need for treatment with daily NSAIDs or antiplatelet agent (ibuprofen < 1200 mg/day, aspirin ≤ 160 mg/day or clopidogrel ≤ 75 mg/day are permitted)
  • Treatment with therapeutic doses of anticoagulants for > 72 hours
  • Mechanical heart valve
  • Antiphospholipid syndrome
  • Sulphite sensitivity
  • Lactose sensitivity
  • Life expectancy < 1 year
  • Unable or unwilling to provide informed consent

Trial locations and contacts

5 sites in 1 country.

5 sites in 1 country

Canada5 sites

  • Hamilton General Hospital

    Hamilton, Ontario, L8L 2X2

  • Juravinski Hospital and Cancer Centre

    Hamilton, Ontario, L8V 1C3

  • Sir Mortimer B. Davis Jewish General Hospital

    Montréal, Ontario, H3T 1E2

  • The Ottawa Hospital - Ottawa Hospital Research Institute (OHRI)

    Ottawa, Ontario

  • Sunnybrook Health Sciences Centre

    Toronto, Ontario, M4N 3M5

Other trials in Canada

About this study

Official title: Tinzaparin Lead-In to Prevent the Post-Thrombotic Syndrome Phase IV Pilot Study

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).

Read the detailed description

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.

Being tested
tinzaparin, Rivaroxaban
Keywords
tinzaparin
Medical subject headings
Venous Thrombosis, Postthrombotic Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • tinzaparinDrug

    low molecular weight heparin

  • RivaroxabanDrug

    direct oral anticoagulant

Study groups in NCT04794569
Study groupRoleWhat they receive
TinzaparinExperimentalinitial 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
Receives: Drug: tinzaparin
RivaroxabanActive comparatorDirect oral anticoagulant only (rivaroxaban 15mg po BID for 3 weeks followed by rivaroxaban 20mg po daily ) for at least 3 months
Receives: Drug: Rivaroxaban

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 6 months post randomization

  2. 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.

    Measured: 3 months post randomization

Secondary outcomes (9)

  1. PTS severity

    The Villalta scale will be used to grade the severity of PTS (mild, moderate, severe) at 6 months post randomization.

    Measured: 6 months post randomization

  2. Villalta score at 10 days

    Villalta score at 10 days

    Measured: 10 days post randomization

  3. 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

    Measured: Two time points: at 10 days and at 3 months post randomization

  4. 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).

    Measured: Two time points: at 10 days and at 3 months post randomization

  5. 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).

    Measured: Two time points: at 3 weeks and at 6 months post randomization

  6. 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'.

    Measured: Three time points: at 3 weeks and at 6 months post randomization

  7. 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'.

    Measured: Three time points: at 3 weeks and at 6 months post randomization

  8. 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.

    Measured: baseline to 6 months post randomization

  9. 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.

    Measured: 6 months post randomization

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted12 Mar 2021
  2. Study start15 Nov 2021
  3. Primary completion19 Jan 2024
  4. Study completion19 Jan 2024

Why it stopped: funding discontinued

Resources

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 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Outcomes assessor
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04794569
Sponsor's protocol ID
3315
Acronym
TILE
Status last verified
Jun 2023
First submitted
24 Feb 2021
Last updated
4 Apr 2024
Results posted
No
Data monitoring committee
Yes
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 32230912

  • 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.

    PubMed 25246013

  • 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.

    PubMed 23615656

  • 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.

    PubMed 19175497

  • 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.

    PubMed 37907305

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing tinzaparin and Rivaroxaban in people with Deep Vein Thrombosis and Post Thrombotic Syndrome, run by Sunnybrook Health Sciences Centre at 5 sites in Canada.

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 20 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: stopped early, as of the sponsor's last update on 4 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 5 sites in Canada. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

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 was stopped early (reason given: funding discontinued). Results are not available in the source record.

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?

PTS at 6 months (time frame: 6 months post randomization). The study lists 2 primary outcomes in all. 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 NCT04794569, which also lists 5 linked publications.

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 4 Apr 2024.

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