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Recently, the multinational, Phase III, open-label, randomised controlled CATCH trial (Comparison of Acute Treatments in Cancer Haemostasis, NCT01130025) was launched comparing tinzaparin with warfarin for the extended treatment of cancer associated thrombosis. The primary objective of the study is to assess the efficacy of tinzaparin in preventing recurrent venous thromboembolism (VTE) in patients with active cancer and acute, symptomatic proximal deep vein thrombosis and/or pulmonary embolism.

In addition to this, the study will also evaluate the safety of tinzaparin given over 6 months; assess clinical and laboratory markers for recurrent VTE and major bleeding and analyse the 6-month overall mortality, the incidence and severity of post-thrombotic syndrome (PTS), the patient-reported quality of life and the healthcare resource utilization (see also figure of study design).

The study is being conducted in 160 sites across 5 continents and randomises 900 patients with active cancer and a histologically or cytologically confirmed solid tumor or hematological malignancy with symptomatic and objectively confirmed acute proximal deep vein thrombosis (DVT) and /or pulmonary embolism (PE) to a treatment with tinzaparin (175 IU/kg once daily; N=450) or warfarin (once daily [target INR 2.0-3.0], overlapping with initial tinzaparin 175 IU/kg once daily for 5-10 days; N=450). All patients in the study are followed up for the primary composite efficacy endpoint and for all-cause death up to day 180 from day of randomisation or death (whichever occurs first), regardless of the study drug status. The main aim of the CATCH trial is to confirm the superior efficacy of tinzaparin over warfarin for the secondary prevention of VTE in patients with active cancer. CATCH will extend and broaden the findings from previous clinical trials comparing LMWH with a VKA such as warfarin by addressing several current knowledge gaps in the management of VTE in patients with cancer. These include the generation of prospective data on the clinical significance of incidental VTE and the potential identification of risk factors predicting recurrence, both of which will add information that may help to further tailor therapy. CATCH will also include specific assessment of the incidence and severity of PTS in patients with cancer. This has not previously been performed despite PTS being a common and burdensome complication of DVT. Little information exists concerning the needs and preferences of cancer patients at risk of recurrent VTE. As such, the patient-reported outcomes from CATCH will provide important insights into quality of life aspects of patient care. Finally, unlike the CLOT trial, which used a reduced dose of dalteparin after 1 month, CATCH will use tinzaparin at the full therapeutic dose during 6 months.

In summary, the results obtained from the CATCH trial will add significantly to the knowledge of the efficacy, safety and cost effectiveness of the LMWH tinzaparin in the prevention of recurrent VTE in cancer patients. The findings should provide greater therapeutic choice and better understanding of the long-term outcomes of patients with cancer and thrombosis.

Literature

A. Lee, R. Bauersachs, M. Janas et al. CATCH: a randomised clinical trial comparing long-term tinzaparin versus warfarin for treatment of acute venous thromboembolism in cancer patients. BMC Cancer 2013;13:284.

 

image2The subcommittee on Haemostasis and Malignancy of the scientific and standardization committee (SSC) of the International Society on Thrombosis and Haemostasis (ISTH) recently published a manuscript giving guidance on common clinical problems complicating the management of anticoagulation in patients with cancer-associated thrombosis.

Although low molecular weight heparins (LMWH) significantly improved patient outcomes and simplify therapy, high-quality evidence on the optimal management of cancer-associated thrombosis is still lacking. The guidelines at hand specifically address the management of challenging cases of patients with cancer-associated thrombosis, including:

  1. treatment of recurrent cancer-associated thrombosis, despite anticoagulation.
  2. VTE management in patients with thrombocytopenia.
  3. VTE management in patients with active bleeding.
  4. the role of inferior vena cava (IVC) filters.

In addition to this, these new treatment guidelines also address the use of novel oral anticoagulants (NOACs) for the treatment of deep vein thrombosis (DVT) and pulmonary embolism (PE). These NOACs include the direct Xa inhibitors rivaroxaban, apixaban, endoxaban and the direct thrombin inhibitor dabigatran. Given the lack of data on the use of these NOACs in cancer patients, the committee recommends against the use of NOACs for the initial and/or long-term treatment of cancer associated thrombosis.

The need to investigate the efficacy and safety of NOACs in randomized is emphasized, controlled clinical trials in cancer patients with VTE, with particular emphasis on drug-drug interactions with anti-neoplastic agents.
Some of the topics discussed in this article have already been covered in previously published consensus guidelines (NCCN, ASCO, ESMO, ISTH guidelines). As such, the aim of this guidance statement was more to outline expert experience and biological rationale that may influence decision-making and offer concrete approaches on the management of anticoagulation in therapeutically challenging cancer patients. Recognizing the lack of high-quality evidence in many of these areas, it is important that patients are informed of the uncertainties, risks and benefits of the management plan.

Literature

M. Carrier, A. Khorana, J. Zwicker et al. Management of challenging cases of patients with cancer-associated thrombosis including recurrent thrombosis and bleeding: guidance from the SSC of the ISTH. J Thromb Haemost 2013;epub ahead of print.

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Acutely ill hospitalized patients are at risk for venous thromboembolism (VTE). Recently, two practical iPad/iPhone app’s were developed by researchers of the IMPROVE study that calculate the risk of a venous thromboembolism. The first, called the IMPROVE VTE Predictive Model app, provides an estimate of the probability of clinically evident acute venous thromboembolism. The second, called the IMPROVE VTE Associative Model app, provides an estimate of the associated rate of clinically evident acute VTE from the time of hospital admission to discharge.

The International Medical Prevention Registry on Venous Thromboembolism (IMPROVE) is a prospective cohort study of physician practices in the provision of prophylaxis against venous thromboembolism (VTE) in hospitalized patients. In a publication by Spyropoulos et al from 2011, the incidence of VTE in the observational IMPROVE study was assessed, and VTE risk-assessment scores at admission and associative VTE scores during hospitalization were determined. Based on the findings from this study, the IMPROVE researchers developed two iPad/iPhone applications that calculate the risk of a venous thromboembolism. One of these apps, the IMPROVE VTE Predictive Model app provides an estimate of the probability of clinically evident acute VTE. The second, called the IMPROVE VTE Associative Model app, provides an estimate of the associated rate of clinically evident acute VTE from the time of hospital admission to discharge.

app1            app2

Data from 15,156 medical patients were analyzed to determine the cumulative incidence of clinically observed VTE over 3 months after admission. Of the 184 patients who developed symptomatic VTE, 76 had pulmonary embolism and 67 lower-extremity DVT. Cumulative VTE incidence was 1.0%; 45% of events occurred post-discharge. The factors independently associated with VTE included previous VTE, known thrombophilia, presence of cancer, age older than 60, lower limb paralysis, immobilization for 7 days or longer and admission to an intensive/coronary care unit. Points were assigned to each factor identified to give a total risk score for each patient. At admission, 67% of patients had a score of 1 or higher. During hospitalization, 31% had a score of 2 or higher. For patients with a score of 2 or 3, the observed VTE risk was 1.5% compared with a risk of 5.7% for patients with a score of 4 or more.1

The first co-called IMPROVE VTE Predictive Model app provides an estimate of the probability of clinically evident acute venous thromboembolism from the time of hospital admission to 90 days post hospital discharge in patients who were admitted with a medical illness. The score in these apps is based on the four risk factors recognized at the time of hospital admission (previous VTE, thrombophilia, current cancer and age over 60 years).2 The second IMPROVE VTE Associative Model app provides an estimate of the associated rate of clinically evident acute venous thromboembolism from the time of hospital admission to discharge, based on risk factors recognized both prior to and during the course of hospitalization.3 Of note, both scores used in these risk calculators still need external validation. Both apps are freely available in the iTunes store and are compatible with iPhone, iPad and iPodTouch with iOS 3.3.3 or later.

Download VTE Predictive Model in the App Store >

Download VTE Associative Model in the App Store >

Literature

  1. A. Spyropoulos, F. Anderson, G. Fitzgerald et al. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest 2011;140(3):706-14.
  2. https://itunes.apple.com/nl/app/vte-predictive-model/id435864673?mt=8
  3. https://itunes.apple.com/us/app/vte-associative-model/id435864550?mt=8


 


image4aWatch the videoclip with professor A. AwadaTake home messages

    • Renal impairment is frequently observed in cancer patients

 

    • LMWHs are the cornerstone of VTE treatment of cancer patients. Besides acute treatment, a maintenance therapy may be given during 3-6 months

 

    • LMWHs with a higher molecular weight are less prone to bioaccumulation leading to bleeding events in patients with renal impairment compared with lighter chain LMWHs whose excretion is highly dependent on the renal function.