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

This study is currently recruiting participants. (see Contacts and Locations)
Verified September 2014 by Ottawa Hospital Research Institute
Sponsor:
Collaborator:
Heart and Stroke Foundation of Ontario
Information provided by (Responsible Party):
Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier:
NCT01602445
First received: May 16, 2012
Last updated: September 8, 2014
Last verified: September 2014
  Purpose

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
Venous Thromboembolism
Deep-Vein Thrombosis
Pulmonary Embolism
Cancer

Study Type: Observational
Study Design: 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

Resource links provided by NLM:


Further study details as provided by Ottawa Hospital Research Institute:

Primary Outcome Measures:
  • Relative changes on biochemical markers [ Time Frame: at initiation of anticoagulation (baseline); at 7 +/- 2 days; 28 +/- 2 days; 35 +/- 2 days; 90 +/- 2 days; and 180 +/- 2 days after initiation of anticoagulation. ] [ Designated as safety issue: No ]

    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.
    5. Tissue Factor antigen.

    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:
  • Rates of treatment failure [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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.

  • Correlation between treatment failure and markers [ Time Frame: 3 years ] [ Designated as safety issue: No ]
    This outcome will be assessed by determining the best cutoff for each marker that would correctly classify success or failure to anticoagulation treatment

  • Compliance to anticoagulation treatment [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Compliance to medication will be measured by validated Questionnaires of compliance (MARS and SEAMS scales)and by patient interview.


Biospecimen Retention:   Samples With DNA

serum specimens


Estimated Enrollment: 700
Study Start Date: July 2012
Estimated Study Completion Date: June 2015
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Groups/Cohorts
Cancer patients
All cancer patients with a diagnosed acute symptomatic VTE episode.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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.

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01602445

Contacts
Contact: Anne M Clement, RN 613-737-8899 ext 73389 amclement@ohri.ca

Locations
Canada, Nova Scotia
Capital Health District Authority Recruiting
Halifax, Nova Scotia, Canada
Principal Investigator: Sudeep Shivakumar, MD         
Canada, Ontario
Hamilton Health Sciences Recruiting
Hamilton, Ontario, Canada, L8L 0A6
Principal Investigator: Peter Gross, MD         
London Health Science Centre Recruiting
London, Ontario, Canada, N6A 5W9
Principal Investigator: Martha Louzada, MD         
The Ottawa Hospital Recruiting
Ottawa, Ontario, Canada, K1H 8L6
Contact: Anne M Clement, RN    613-798-5555 ext 19841    amclement@ohri.ca   
Sub-Investigator: Marc Carrier, MD         
Sub-Investigator: Marc Rodger, MD         
Sub-Investigator: Alan Karovitch, MD         
Sub-Investigator: Carol Gonsalves, MD         
Sub-Investigator: Dimitrios Scarvelis, MD         
Sub-Investigator: Catherine Code, MD         
Sub-Investigator: Melissa Forgie, MD         
Sub-Investigator: Esteban Gandara, MD         
Sub-Investigator: Timothy Ramsay, PhD         
Principal Investigator: Phil S Wells, MD         
Canada, Quebec
CHUM-Notre-Dame Hospital Recruiting
Montreal, Quebec, Canada
Principal Investigator: Normand Blais, MD         
Sponsors and Collaborators
Ottawa Hospital Research Institute
Heart and Stroke Foundation of Ontario
Investigators
Principal Investigator: Philip S Wells, MD Ottawa Hospital Research Institute
  More Information

Publications:
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.

Responsible Party: Ottawa Hospital Research Institute
ClinicalTrials.gov Identifier: NCT01602445     History of Changes
Other Study ID Numbers: HSFO-000524, 20120208-01H
Study First Received: May 16, 2012
Last Updated: September 8, 2014
Health Authority: Canada: Ethics Review Committee

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

Additional relevant MeSH terms:
Venous Thromboembolism
Venous Thrombosis
Pulmonary Embolism
Recurrence
Thromboembolism
Thrombosis
Cardiovascular Diseases
Disease Attributes
Embolism
Embolism and Thrombosis
Lung Diseases
Pathologic Processes
Respiratory Tract Diseases
Vascular Diseases
Coagulants
Hematologic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014