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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01602445
Recruitment Status : Completed
First Posted : May 21, 2012
Last Update Posted : May 11, 2017
Heart and Stroke Foundation of Ontario
Information provided by (Responsible Party):
Ottawa Hospital Research Institute

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.

Condition or disease
Venous Thromboembolism Deep-Vein Thrombosis Pulmonary Embolism Cancer

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.

Study Type : Observational
Estimated Enrollment : 700 participants
Observational Model: Cohort
Time Perspective: Prospective
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 Start Date : July 2012
Actual Primary Completion Date : October 2016
Actual Study Completion Date : October 2016

Cancer patients
All cancer patients with a diagnosed acute symptomatic VTE episode.

Primary Outcome Measures :
  1. Relative changes on biochemical markers [ Time Frame: 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. ]

    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.

Secondary Outcome Measures :
  1. Rates of treatment failure [ Time Frame: 6 months ]
    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.

  2. Correlation between treatment failure and markers [ Time Frame: 6 months after treatment failure ]
    This outcome will be assessed by determining the best cutoff for each marker that would correctly classify success or failure to anticoagulation treatment

  3. Compliance to anticoagulation treatment [ Time Frame: 6 months ]
    Compliance to medication will be measured by review of the patient medication diary.

Biospecimen Retention:   Samples With DNA
Serum specimens Optional DNA banking

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT01602445

Canada, Nova Scotia
Capital Health District Authority
Halifax, Nova Scotia, Canada
Canada, Ontario
Hamilton Health Sciences
Hamilton, Ontario, Canada, L8L 0A6
London Health Science Centre
London, Ontario, Canada, N6A 5W9
The Ottawa Hospital
Ottawa, Ontario, Canada, K1H 8L6
Canada, Quebec
CHUM-Notre-Dame Hospital
Montreal, Quebec, Canada
Sponsors and Collaborators
Ottawa Hospital Research Institute
Heart and Stroke Foundation of Ontario
Principal Investigator: Philip S Wells, MD Ottawa Hospital Research Institute

Publications of Results:
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.

Other Publications:

Responsible Party: Ottawa Hospital Research Institute Identifier: NCT01602445     History of Changes
Other Study ID Numbers: HSFO-000524
20120208-01H ( Other Identifier: Ottawa Hospital Research Ethics Board )
First Posted: May 21, 2012    Key Record Dates
Last Update Posted: May 11, 2017
Last Verified: May 2017
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Keywords provided by Ottawa Hospital Research Institute:
Venous Thrombosis
Coagulation factors

Additional relevant MeSH terms:
Venous Thrombosis
Venous Thromboembolism
Pulmonary Embolism
Embolism and Thrombosis
Vascular Diseases
Cardiovascular Diseases
Disease Attributes
Pathologic Processes
Lung Diseases
Respiratory Tract Diseases