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

Cancer Clinical Trial

— REMARK  

Official title:

Analysis of Pro-coagulant and Thrombin-generation Markers for the Prediction of Therapeutic Failure in Cancer Patients at Risk for Recurrence of Venous Thromboembolism: A Pilot Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01602445
• Other study ID #: HSFO-000524
• Secondary ID: 20120208-01H
• Status: Completed
• Phase: N/A
• First received: May 16, 2012
• Last updated: May 9, 2017
• Start date: July 2012
• Est. completion date: October 2016

Study information

• Verified date: May 2017
• Source: Ottawa Hospital Research Institute
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 700
• Est. completion date: October 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Cancer
• Deep-Vein Thrombosis
• Embolism
• Pulmonary Embolism
• Recurrence
• Thromboembolism
• Thrombosis
• Venous Thromboembolism
• Venous Thrombosis

Locations

Country	Name	City	State
Canada	Capital Health District Authority	Halifax	Nova Scotia
Canada	Hamilton Health Sciences	Hamilton	Ontario
Canada	London Health Science Centre	London	Ontario
Canada	CHUM-Notre-Dame Hospital	Montreal	Quebec
Canada	The Ottawa Hospital	Ottawa	Ontario

Sponsors (2)

Lead Sponsor	Collaborator
Ottawa Hospital Research Institute	Heart and Stroke Foundation of Ontario

Country where clinical trial is conducted

Canada, 

References & Publications (10)

Blom JW, Vanderschoot JP, Oostindiër 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. — View Citation

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

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. — View Citation

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. — View Citation

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 ven — View Citation

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 venou

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

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. Epub 2002 Jul 12. — View Citation

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. — View Citation

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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Relative changes on biochemical markers	The following pro-coagulant and thrombin-generation markers will be measured: Prothrombin fragments F1+2; D-dimer,; thrombin-antithrombin (TAT); 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	Rates of treatment failure	This outcome will be measured by the proportion of cancer patients who might develop recurrent VTE while on 6-month treatment with anticoagulation within the time-frame of the study.	6 months
Secondary	Correlation between treatment failure and markers	This outcome will be assessed by determining the best cutoff for each marker that would correctly classify success or failure to anticoagulation treatment	6 months after treatment failure
Secondary	Compliance to anticoagulation treatment	Compliance to medication will be measured by review of the patient medication diary.	6 months