Pro-coagulant Markers and Anticoagulant Failure in Cancer Patients at Risk for Recurrence of Venous Thromboembolism (REMARK)
9 mai 2017 mis à jour par: Ottawa Hospital Research Institute
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
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.
Aperçu de l'étude
Statut
Complété
Description détaillée
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.
Type d'étude
Observationnel
Inscription (Anticipé)
700
Contacts et emplacements
Cette section fournit les coordonnées de ceux qui mènent l'étude et des informations sur le lieu où cette étude est menée.
Lieux d'étude
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Nova Scotia
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Halifax, Nova Scotia, Canada
- Capital Health District Authority
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Ontario
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Hamilton, Ontario, Canada, L8L 0A6
- Hamilton Health Sciences
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London, Ontario, Canada, N6A 5W9
- London Health Science Centre
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Ottawa, Ontario, Canada, K1H 8L6
- The Ottawa Hospital
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Quebec
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Montreal, Quebec, Canada
- CHUM-Notre-Dame Hospital
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Critères de participation
Les chercheurs recherchent des personnes qui correspondent à une certaine description, appelée critères d'éligibilité. Certains exemples de ces critères sont l'état de santé général d'une personne ou des traitements antérieurs.
Critère d'éligibilité
Âges éligibles pour étudier
18 ans et plus (Adulte, Adulte plus âgé)
Accepte les volontaires sains
Non
Sexes éligibles pour l'étude
Tout
Méthode d'échantillonnage
Échantillon non probabiliste
Population étudiée
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.
La description
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.
Plan d'étude
Cette section fournit des détails sur le plan d'étude, y compris la façon dont l'étude est conçue et ce que l'étude mesure.
Comment l'étude est-elle conçue ?
Détails de conception
Cohortes et interventions
Groupe / Cohorte |
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Cancer patients
All cancer patients with a diagnosed acute symptomatic VTE episode.
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Que mesure l'étude ?
Principaux critères de jugement
Mesure des résultats |
Description de la mesure |
Délai |
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Relative changes on biochemical markers
Délai: 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.
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The following pro-coagulant and thrombin-generation markers will be measured:
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.
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Mesures de résultats secondaires
Mesure des résultats |
Description de la mesure |
Délai |
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Rates of treatment failure
Délai: 6 months
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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.
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6 months
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Correlation between treatment failure and markers
Délai: 6 months after treatment failure
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This outcome will be assessed by determining the best cutoff for each marker that would correctly classify success or failure to anticoagulation treatment
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6 months after treatment failure
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Compliance to anticoagulation treatment
Délai: 6 months
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Compliance to medication will be measured by review of the patient medication diary.
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6 months
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Collaborateurs et enquêteurs
C'est ici que vous trouverez les personnes et les organisations impliquées dans cette étude.
Parrainer
Collaborateurs
Les enquêteurs
- Chercheur principal: Philip S Wells, MD, Ottawa Hospital Research Institute
Publications et liens utiles
La personne responsable de la saisie des informations sur l'étude fournit volontairement ces publications. Il peut s'agir de tout ce qui concerne l'étude.
Publications générales
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Dates d'enregistrement des études
Ces dates suivent la progression des dossiers d'étude et des soumissions de résultats sommaires à ClinicalTrials.gov. Les dossiers d'étude et les résultats rapportés sont examinés par la Bibliothèque nationale de médecine (NLM) pour s'assurer qu'ils répondent à des normes de contrôle de qualité spécifiques avant d'être publiés sur le site Web public.
Dates principales de l'étude
Début de l'étude
1 juillet 2012
Achèvement primaire (Réel)
1 octobre 2016
Achèvement de l'étude (Réel)
1 octobre 2016
Dates d'inscription aux études
Première soumission
16 mai 2012
Première soumission répondant aux critères de contrôle qualité
17 mai 2012
Première publication (Estimation)
21 mai 2012
Mises à jour des dossiers d'étude
Dernière mise à jour publiée (Réel)
11 mai 2017
Dernière mise à jour soumise répondant aux critères de contrôle qualité
9 mai 2017
Dernière vérification
1 mai 2017
Plus d'information
Termes liés à cette étude
Termes MeSH pertinents supplémentaires
Autres numéros d'identification d'étude
- HSFO-000524
- 20120208-01H (Autre identifiant: Ottawa Hospital Research Ethics Board)
Plan pour les données individuelles des participants (IPD)
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INDÉCIS
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