Tinzaparin Lead-In to Prevent the Post-Thrombotic Syndrome

NCT04794569 | Terminated Phase 4 DMC

• 1 other identifier: 3315
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 5

Brief 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).

Conditions

Deep Vein Thrombosis; Post Thrombotic Syndrome

Keywords

tinzaparin

Outcome Measures

Primary Outcomes (2)

• 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

Secondary Outcomes (9)

• PTS severity

  6 months post randomization

• Villalta score at 10 days

  10 days post randomization

• DVT-related leg pain

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

• Global Improvement

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

• Patient's satisfaction with treatment

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

Other Outcomes (1)

• Health Services Research Issues

  6 months post randomization

Study Arms (2)

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

Drug: tinzaparin

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

Drug: Rivaroxaban

Interventions

tinzaparin DRUG

low molecular weight heparin

Tinzaparin

Rivaroxaban DRUG

direct oral anticoagulant

Rivaroxaban

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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)

You may not qualify if:

• 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)
• 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

Sponsors & Collaborators

• Sunnybrook Health Sciences Centre: lead
• LEO Pharma: collaborator
• Sunnybrook Research Institute: collaborator

Study Sites (5)

Hamilton General Hospital

Hamilton, Ontario, L8L 2X2, Canada

Location

Juravinski Hospital and Cancer Centre

Hamilton, Ontario, L8V 1C3, Canada

Location

Sir Mortimer B. Davis Jewish General Hospital

Montréal, Ontario, H3T 1E2, Canada

Location

The Ottawa Hospital - Ottawa Hospital Research Institute (OHRI)

Ottawa, Ontario, Canada

Location

Sunnybrook Health Sciences Centre

Toronto, Ontario, M4N 3M5, Canada

Location

Related Publications (5)

• 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.

  PMID: 32230912 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.

  PMID: 25246013 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.

  PMID: 23615656 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.

  PMID: 19175497 BACKGROUND

• 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.

  PMID: 37907305 DERIVED

MeSH Terms

Conditions

Venous Thrombosis; Postthrombotic Syndrome

Interventions

Tinzaparin; Rivaroxaban

Condition Hierarchy (Ancestors)

Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Venous Insufficiency

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Heparin; Glycosaminoglycans; Polysaccharides; Carbohydrates; Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• 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

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Patients will be instructed not to disclose their treatment to PTS assessors
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2021
• First Posted: March 12, 2021
• Study Start: November 15, 2021
• Primary Completion: January 19, 2024
• Study Completion: January 19, 2024
• Last Updated: April 4, 2024

Record last verified: 2023-06

Data Sharing

• IPD Sharing: Will not share

Locations

CA (5)