Clinical trial NCT04794569: Tinzaparin Lead-In to Prevent the Post-Thrombotic Syndrome
Official title: Tinzaparin Lead-In to Prevent the Post-Thrombotic Syndrome Phase IV Pilot Study
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Deep Vein Thrombosis
Post Thrombotic Syndrome
Keywords: tinzaparin
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: LEO Pharma
name: Sunnybrook Research Institute
First posted: 2021-03-12
Enrollment: 9
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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).

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.

Eligibility criteria: 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:

1. Age \< 18 years
2. History of ipsilateral DVT (distal and/or proximal)
3. Active cancer
4. Thrombolysis or other invasive early thrombus removal technique to treat DVT or PE
5. Pregnant or breast feeding
6. Impaired renal function (creatinine clearance \< 30 ml/min according to Cockcroft-Gault formula)
7. Concomitant use of drugs that interact with rivaroxaban (i.e. keto- or itraconazole, ritonavir)
8. Allergy or hypersensitivity to heparin or rivaroxaban, including heparin induced thrombocytopenia
9. 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)
10. Thrombocytopenia (platelet count \< 100 x 109/L)
11. Liver disease (including Child-Pugh Class B and Class C) associated with coagulopathy
12. Body weight \> 120 kg or \< 40 kg
13. Need for treatment with daily NSAIDs or antiplatelet agent (ibuprofen \< 1200 mg/day, aspirin ≤ 160 mg/day or clopidogrel ≤ 75 mg/day are permitted)
14. Treatment with therapeutic doses of anticoagulants for \> 72 hours
15. Mechanical heart valve
16. Antiphospholipid syndrome
17. Sulphite sensitivity
18. Lactose sensitivity
19. Life expectancy \< 1 year
20. Unable or unwilling to provide informed consent

Primary outcomes:
measure: PTS at 6 months
timeFrame: 6 months post randomization
measure: Main feasibility
timeFrame: 3 months post randomization
Secondary outcomes:
measure: PTS severity
timeFrame: 6 months post randomization
measure: Villalta score at 10 days
timeFrame: 10 days post randomization
measure: DVT-related leg pain
timeFrame: Two time points: at 10 days and at 3 months post randomization
measure: Global Improvement
timeFrame: Two time points: at 10 days and at 3 months post randomization
measure: Patient's satisfaction with treatment
timeFrame: Two time points: at 3 weeks and at 6 months post randomization
measure: QOL (Quality of Life) score - SF-36
timeFrame: Three time points: at 3 weeks and at 6 months post randomization
measure: QOL (Quality of Life) score - VEINES-QOL
timeFrame: Three time points: at 3 weeks and at 6 months post randomization
measure: SAEs
timeFrame: baseline to 6 months post randomization
measure: Rate of lost to follow-up
timeFrame: 6 months post randomization
Other outcomes:
measure: Health Services Research Issues
timeFrame: 6 months post randomization
Locations:
city: Hamilton
country: Canada
facility: Hamilton General Hospital
state: Ontario
city: Hamilton
country: Canada
facility: Juravinski Hospital and Cancer Centre
state: Ontario
city: Montréal
country: Canada
facility: Sir Mortimer B. Davis Jewish General Hospital
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital - Ottawa Hospital Research Institute (OHRI)
state: Ontario
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Centre (Toronto, Ontario, Canada)
name: Jean-Philippe Galanaud, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Jewish General Hospital (Montreal, Quebec, Canada)
name: Susan R Kahn, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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. Erratum In: Circulation. 2015 Feb 24;131(8):e359. doi: 10.1161/CIR.0000000000000185.
citation: 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.
citation: 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.