Pro-coagulant Markers and Anticoagulant Failure in Cancer Patients at Risk for Recurrence of Venous Thromboembolism

NCT01602445 | Completed

• 2 other identifiers: HSFO-00052420120208-01H
• Study Type: observational
• Target: 700
• Locations: 1 country
• Sites: 5

Brief Summary

The presence of clots in the veins of arms and/or legs or lungs of Cancer patients decreases their quality of life, delays their treatment and may cause death. The best way to avoid new clots is by giving blood thinners before clots are formed, but even some patients who are taking blood thinners may form blood clots. A major problem is that it is difficult to know which patients form clots while they are receiving blood thinners, a situation called treatment failure. Several studies have shown that by doing blood tests that measure the formation of clots, the investigators could know if the patient is responding to the blood thinners. If this is proven, the investigators will be able to apply these tests to all patients.

Conditions

Venous Thromboembolism; Deep-Vein Thrombosis; Pulmonary Embolism; Cancer

Keywords

Venous Thrombosis; Coagulation factors; Cancer; Blood

Outcome Measures

Primary Outcomes (1)

• Relative changes on biochemical markers

  The following pro-coagulant and thrombin-generation markers will be measured: 1. Prothrombin fragments F1+2; 2. D-dimer, 3. thrombin-antithrombin (TAT) 4. Soluble P-selectin. For each patient, we will calculate baseline values and the relative changes (delta) of procoagulant and thrombin generation markers. The relative changes (delta) will be defined by the percentage of change in the marker at each visit relative to baseline measurement.

  at initiation of anticoagulation (baseline); at 7-14 days; 21-35 days; 37- 44 days; 83-97 days; and 173-187 days after initiation of anticoagulation.

Secondary Outcomes (3)

• Rates of treatment failure

  6 months

• Correlation between treatment failure and markers

  6 months after treatment failure

• Compliance to anticoagulation treatment

  6 months

Study Arms (1)

Cancer patients

All cancer patients with a diagnosed acute symptomatic VTE episode.

Eligibility Criteria

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

Study Population

Referrals of cancer patients to the Thrombosis clinic at each participating center at the time that an acute episode of VTE has been confirmed ( within 0 +/- 1 day) from the start of anticoagulation treatment. Our centers provide VTE treatment for all the cancer patients in our regions given the design of the Ontario Cancer Program, ensuring a generalizable patient population.

You may qualify if:

• Patients with any type of cancer (except basal cell and squamous cell carcinoma of the skin) and at any stage of the disease or treatment
• Confirmed newly diagnosed acute symptomatic VTE (proximal DVT, PE, Arm DVT, Multiple SSPE only)
• Planned treatment of VTE with low-molecular weight heparin (LMWH)
• Age 18 years old or older.

You may not qualify if:

• Planned cell transplant
• Patient receiving anticoagulation due to other clinical indications
• Patient who has received more than one therapeutic dose of LMWH
• Unable or unwilling to provide written, informed consent.

Sponsors & Collaborators

• Ottawa Hospital Research Institute: lead
• Heart and Stroke Foundation of Ontario: collaborator

Study Sites (5)

Capital Health District Authority

Halifax, Nova Scotia, Canada

Location

Hamilton Health Sciences

Hamilton, Ontario, L8L 0A6, Canada

Location

London Health Science Centre

London, Ontario, N6A 5W9, Canada

Location

The Ottawa Hospital

Ottawa, Ontario, K1H 8L6, Canada

Location

CHUM-Notre-Dame Hospital

Montreal, Quebec, Canada

Location

Related Publications (10)

• Noble S, Pasi J. Epidemiology and pathophysiology of cancer-associated thrombosis. Br J Cancer. 2010 Apr 13;102 Suppl 1(Suppl 1):S2-9. doi: 10.1038/sj.bjc.6605599.

  PMID: 20386546 BACKGROUND

• Blom JW, Vanderschoot JP, Oostindier MJ, Osanto S, van der Meer FJ, Rosendaal FR. Incidence of venous thrombosis in a large cohort of 66,329 cancer patients: results of a record linkage study. J Thromb Haemost. 2006 Mar;4(3):529-35. doi: 10.1111/j.1538-7836.2006.01804.x.

  PMID: 16460435 BACKGROUND

• Prandoni P, Lensing AW, Piccioli A, Bernardi E, Simioni P, Girolami B, Marchiori A, Sabbion P, Prins MH, Noventa F, Girolami A. Recurrent venous thromboembolism and bleeding complications during anticoagulant treatment in patients with cancer and venous thrombosis. Blood. 2002 Nov 15;100(10):3484-8. doi: 10.1182/blood-2002-01-0108. Epub 2002 Jul 12.

  PMID: 12393647 BACKGROUND

• Coleman R, MacCallum P. Treatment and secondary prevention of venous thromboembolism in cancer. Br J Cancer. 2010 Apr 13;102 Suppl 1(Suppl 1):S17-23. doi: 10.1038/sj.bjc.6605601.

  PMID: 20386545 BACKGROUND

• Lee AY, Levine MN, Baker RI, Bowden C, Kakkar AK, Prins M, Rickles FR, Julian JA, Haley S, Kovacs MJ, Gent M; Randomized Comparison of Low-Molecular-Weight Heparin versus Oral Anticoagulant Therapy for the Prevention of Recurrent Venous Thromboembolism in Patients with Cancer (CLOT) Investigators. Low-molecular-weight heparin versus a coumarin for the prevention of recurrent venous thromboembolism in patients with cancer. N Engl J Med. 2003 Jul 10;349(2):146-53. doi: 10.1056/NEJMoa025313.

  PMID: 12853587 BACKGROUND

• Weitz IC, Israel VK, Waisman JR, Presant CA, Rochanda L, Liebman HA. Chemotherapy-induced activation of hemostasis: effect of a low molecular weight heparin (dalteparin sodium) on plasma markers of hemostatic activation. Thromb Haemost. 2002 Aug;88(2):213-20.

  PMID: 12195692 BACKGROUND

• Traby L, Kaider A, Schmid R, Kranz A, Quehenberger P, Kyrle PA, Eichinger S. The effects of low-molecular-weight heparin at two different dosages on thrombin generation in cancer patients. A randomised controlled trial. Thromb Haemost. 2010 Jul;104(1):92-9. doi: 10.1160/TH09-12-0863. Epub 2010 May 10.

  PMID: 20458441 BACKGROUND

• Kirwan CC, McDowell G, McCollum CN, Kumar S, Byrne GJ. Early changes in the haemostatic and procoagulant systems after chemotherapy for breast cancer. Br J Cancer. 2008 Oct 7;99(7):1000-6. doi: 10.1038/sj.bjc.6604620. Epub 2008 Sep 2.

  PMID: 18766191 BACKGROUND

• Louzada ML, Carrier M, Lazo-Langner A, Dao V, Zhang J, Kovacs MJ, Lee AY, Levine MN, Meyer G, Rodger M, Wells PS. Validation of a clinical prediction rule for risk stratification of recurrent venous thromboembolism in patients with cancer-associated venous thromboembolism. American Society of Hematology, 52nd Annual Meeting, Orlando Florida, December 4-7, 2010. Abstract 4209. Poster Board III-988.

  RESULT

• Louzada ML, Carrier M, Lazo-Langner A, Dao V, Kovacs MJ, Ramsay TO, Rodger MA, Zhang J, Lee AY, Meyer G, Wells PS. Development of a clinical prediction rule for risk stratification of recurrent venous thromboembolism in patients with cancer-associated venous thromboembolism. Circulation. 2012 Jul 24;126(4):448-54. doi: 10.1161/CIRCULATIONAHA.111.051920. Epub 2012 Jun 7.

  PMID: 22679142 RESULT

Biospecimen

Retention: SAMPLES WITH DNA

Serum specimens Optional DNA banking

MeSH Terms

Conditions

Venous Thromboembolism; Venous Thrombosis; Pulmonary Embolism; Neoplasms

Condition Hierarchy (Ancestors)

Thromboembolism; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Thrombosis; Lung Diseases; Respiratory Tract Diseases; Embolism

Study Officials

• Philip S Wells, MD

  Ottawa Hospital Research Institute

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 16, 2012
• First Posted: May 21, 2012
• Study Start: July 1, 2012
• Primary Completion: October 1, 2016
• Study Completion: October 1, 2016
• Last Updated: May 11, 2017

Record last verified: 2017-05

Locations

CA (5)