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

NCT ID: NCT01602445

Last Updated: 2017-05-11

Basic Information

• Recruitment Status: COMPLETED
• Total Enrollment: 700 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2012-07-31
• Study Completion Date: 2016-10-31

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.

Detailed Description

Therapeutic failure in cancer patients at high risk for recurrence of Venous thromboembolism (VTE) may be as high as 20% and the risk of death from a recurrent episode of pulmonary embolism is at least 8%. Studies that have used pro-coagulant and thrombin generation markers support the notion that cancer is associated with a hypercoagulability state and that intensified doses of anticoagulation may be necessary to suppress this state. Thus, it may be possible that by using these tests, we would identify the patients that do not respond to standard doses of anticoagulation. To date, only few small studies have evaluated the use of pro-coagulant markers in cancer patients but this data is promising. Our study will measure pro-coagulant markers in cancer patients at risk for VTE recurrence to determine if there is a relationship between the changes in the levels of pro-coagulant markers and VTE recurrence while taking anticoagulation with low-molecular weight-heparin (LMWH). The evaluation of the pro-coagulant markers may enable new treatment strategies in cancer patients who fail their initial treatment. Patients will be stratified by a risk model developed by our group and will be validate with this study. This new approach has the potential to improve the recovery of patients, to reduce death and disability due to clots in the veins of legs or arms and/or lungs.

Conditions

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

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Cancer patients

All cancer patients with a diagnosed acute symptomatic VTE episode.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• 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.

Exclusion Criteria

• 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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Heart and Stroke Foundation of Ontario

OTHER

Sponsor Role: collaborator

Ottawa Hospital Research Institute

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Philip S Wells, MD

Role: PRINCIPAL_INVESTIGATOR

Ottawa Hospital Research Institute

Locations

Capital Health District Authority

Halifax, Nova Scotia, Canada

Hamilton Health Sciences

Hamilton, Ontario, Canada

London Health Science Centre

London, Ontario, Canada

The Ottawa Hospital

Ottawa, Ontario, Canada

CHUM-Notre-Dame Hospital

Montreal, Quebec, Canada

Countries

Canada

References

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.

Reference Type: BACKGROUND

PMID: 20386546 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 16460435 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12393647 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20386545 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12853587 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 12195692 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 20458441 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 18766191 (View on PubMed)

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.

Reference Type: 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.

Reference Type: RESULT

PMID: 22679142 (View on PubMed)

Other Identifiers

20120208-01H

Identifier Type: OTHER

Identifier Source: secondary_id

HSFO-000524

Identifier Type: -

Identifier Source: org_study_id