Clinical trial NCT01602445: Pro-coagulant Markers and Anticoagulant Failure in Cancer Patients at Risk for Recurrence of Venous Thromboembolism
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
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Venous Thromboembolism
Deep-Vein Thrombosis
Pulmonary Embolism
Cancer
Keywords: Venous Thrombosis
Coagulation factors
Cancer
Blood
Lead sponsor: Ottawa Hospital Research Institute
Sponsor class: OTHER
Collaborators: name: Heart and Stroke Foundation of Ontario
First posted: 2012-05-21
Enrollment: 700
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
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.

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.

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.

Primary outcomes:
measure: Relative changes on biochemical markers
timeFrame: 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:
measure: Rates of treatment failure
timeFrame: 6 months
measure: Correlation between treatment failure and markers
timeFrame: 6 months after treatment failure
measure: Compliance to anticoagulation treatment
timeFrame: 6 months
Other outcomes:
Locations:
city: Halifax
country: Canada
facility: Capital Health District Authority
state: Nova Scotia
city: Hamilton
country: Canada
facility: Hamilton Health Sciences
state: Ontario
city: London
country: Canada
facility: London Health Science Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital
state: Ontario
city: Montreal
country: Canada
facility: CHUM-Notre-Dame Hospital
state: Quebec
Study officials:
affiliation: Ottawa Hospital Research Institute
name: Philip S Wells, MD
role: PRINCIPAL_INVESTIGATOR
References:
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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.
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.
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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 venous thromboembolism. American Society of Hematology, 52nd Annual Meeting, Orlando Florida, December 4-7, 2010. Abstract 4209. Poster Board III-988.
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 venous thromboembolism. Circulation. 2012 Jul 24;126(4):448-54. doi: 10.1161/CIRCULATIONAHA.111.051920. Epub 2012 Jun 7.