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Edoxaban for treatment of venous thromboembolism in patients with cancer: Rationale and design of the hokusai VTE-cancer study

Published on Aug 13, 2015in Thrombosis and Haemostasis4.733
· DOI :10.1160/TH15-06-0452
Nick van Es17
Estimated H-index: 17
(UvA: University of Amsterdam),
Marcello Di Nisio30
Estimated H-index: 30
+ 20 AuthorsGary E. Raskob73
Estimated H-index: 73
(OU: University of Oklahoma)
Abstract
Direct oral anticoagulants may be effective and safe for treatment of venous thromboembolism (VTE) in cancer patients, but they have not been compared with low-molecular-weight heparin (LMWH), the current recommended treatment for these patients. The Hokusai VTE-cancer study is a randomised, open-label, clinical trial to evaluate whether edoxaban, an oral factor Xa inhibitor, is non-inferior to LMWH for treatment of VTE in patients with cancer. We present the rationale and some design features of the study. One such feature is the composite primary outcome of recurrent VTE and major bleeding during a 12-month study period. These two complications occur frequently in cancer patients receiving anticoagulant treatment and have a significant impact. The evaluation beyond six months will fill the current gap in the evidence base for the long-term treatment of these patients. Based on the observation that the risk of recurrent VTE in patients with active cancer is similar to that in those with a history of cancer, the Hokusai VTE-cancer study will enrol patients if whose cancer was diagnosed within the past two years. In addition, patients with incidental VTE are eligible because their risk of recurrent VTE is similar to that in patients with symptomatic disease. The unique design features of the Hokusai VTE-cancer study should lead to enrolment of a broad spectrum of cancer patients with VTE who could benefit from oral anticoagulant treatment.
  • References (30)
  • Citations (59)
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References30
Newest
#1Catch Investigators (UBC: University of British Columbia)H-Index: 1
Importance Low-molecular-weight heparin is recommended over warfarin for the treatment of acute venous thromboembolism (VTE) in patients with active cancer largely based on results of a single, large trial. Objective To study the efficacy and safety of tinzaparin vs warfarin for treatment of acute, symptomatic VTE in patients with active cancer. Design, Settings, and Participants A randomized, open-label study with blinded central adjudication of study outcomes enrolled patients in 164 centers i...
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#1Charles W. Francis (URMC: University of Rochester Medical Center)H-Index: 69
#2Craig M. Kessler (Georgetown University)H-Index: 33
Last. Ajay K. Kakkar (QMUL: Queen Mary University of London)H-Index: 61
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SummaryBackground Treatment of venous thromboembolism (VTE) in patients with cancer has a high rate of recurrence and bleeding complications. Guidelines recommend low-molecular-weight heparin (LMWH) for at least 3–6 months and possibly indefinitely for patients with active malignancy. There are, however, few data supporting treatment with LMWH beyond 6 months. The primary aim of the DALTECAN study (NCT00942968) was to determine the safety of dalteparin between 6 and 12 months in cancer-associate...
87 CitationsSource
#1Marcello Di NisioH-Index: 30
#2Agnes Y.Y. Lee (VCH: Vancouver Coastal Health)H-Index: 42
Last. Alok A. Khorana (Cleveland Clinic)H-Index: 47
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Modern computer tomography (CT) with its higher sensitivity and resolution has increased the detection of incidental venous thromboembolism (VTE) in the venous and pulmonary vasculature during routine imaging for cancer staging and response assessment [1]. As a result, up to half of all VTEs diagnosed in oncology centers are incidental [1-5]. Although widely accepted, the diagnosis of incidental VTE is made without using the standard imaging studies required for confirming the presence of sympto...
42 CitationsSource
Venous thromboembolism (VTE) is a common occurrence in patients with malignant disease. Standard treatment for acute deep vein thrombosis (DVT) and/or pulmonary embolism (PE) is usually initial subcutaneous weight-adjusted low molecular weight heparin (LMWH), which is continued for approximately 6 months. The treatment of acute DVT and/or PE is to prevent recurrent thromboembolism. In one prospective study, the cumulative incidence of recurrent VTE at 12 months was approximately 20% in patients ...
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#1Elie A. Akl (AUB: American University of Beirut)H-Index: 72
#2Lara A. Kahale (AUB: American University of Beirut)H-Index: 14
Last. Holger J. Schünemann (McMaster University)H-Index: 109
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Background Cancer increases the risk of thromboembolic events, especially in people receiving anticoagulation treatments. Objectives To compare the efficacy and safety of low molecular weight heparins (LMWHs), direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs) for the long-term treatment of venous thromboembolism (VTE) in people with cancer. Search methods We conducted a literature search including a major electronic search of the Cochrane Central Register of Controlled Trials (...
190 CitationsSource
#1Nick van EsH-Index: 17
#2Suzanne M. BlekerH-Index: 9
Last. Marcello Di NisioH-Index: 30
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ABSTRACT Clinically unsuspected pulmonary embolism (UPE) is frequently diagnosed in cancer patients undergoing routine computed tomography scans for staging purposes or treatment response evaluation. The reported incidence of UPE ranges from 1% to 5% which probably represents an underestimation. A significant proportion of cancer patients with UPE actually do have pulmonary embolism (PE) related symptoms. However, these can erroneously be attributed to the cancer itself or to cancer therapy lead...
31 CitationsSource
#1Harry R. BüllerH-Index: 92
#2Pantep Angchaisuksiri (MU: Mahidol University)H-Index: 23
Last. Michele Mercuri (Daiichi Sankyo)H-Index: 26
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![Graphic][1] Low-molecular-weight heparin (LMWH) is recommended for long-term anticoagulant therapy in cancer patients with venous thromboembolism (VTE). These patients have been mostly excluded from clinical trials comparing new oral anticoagulants with vitamin-K antagonists. Hokusai-VTE was a global randomized, double-blind, non-inferiority trial (margin 1.5) that compared edoxaban, an oral factor Xa inhibitor, with warfarin for long-term therapy in 8,292 patients with acute symptomatic proxi...
19 CitationsSource
#1Harry R. BüllerH-Index: 92
#2Hervé DecoususH-Index: 38
Last. Phil WellsH-Index: 5
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Methods In a randomized, double-blind, noninferiority study, we randomly assigned patients with acute venous thromboembolism, who had initially received heparin, to receive edoxaban at a dose of 60 mg once daily, or 30 mg once daily (e.g., in the case of patients with creatinine clearance of 30 to 50 ml per minute or a body weight below 60 kg), or to receive warfarin. Patients received the study drug for 3 to 12 months. The primary efficacy outcome was recurrent symptomatic venous thromboembolis...
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#1Jasmijn F. Timp (LUMC: Leiden University Medical Center)H-Index: 4
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Last. Suzanne C. Cannegieter (LUMC: Leiden University Medical Center)H-Index: 41
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Cancer-associated venous thrombosis is a common condition, although the reported incidence varies widely between studies depending on patient population, start and duration of follow-up, and the method of detecting and reporting thrombotic events. Furthermore, as cancer is a heterogeneous disease, the risk of venous thrombosis depends on cancer types and stages, treatment measures, and patient-related factors. In general, cancer patients with venous thrombosis do not fare well and have an increa...
321 CitationsSource
#1Giancarlo A (University of Perugia)H-Index: 75
#2Harry R. BüllerH-Index: 92
Last. Jeffrey I. WeitzH-Index: 90
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METHODS In this randomized, double-blind study, we compared apixaban (at a dose of 10 mg twice daily for 7 days, followed by 5 mg twice daily for 6 months) with conventional therapy (subcutaneous enoxaparin, followed by warfarin) in 5395 patients with acute venous thromboembolism. The primary efficacy outcome was recurrent symptomatic venous thromboembolism or death related to venous thromboembolism. The principal safety outcomes were major bleeding alone and major bleeding plus clinically relev...
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Cited By59
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#1Frits I. Mulder (UvA: University of Amsterdam)H-Index: 2
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Last. Nick van Es (UvA: University of Amsterdam)H-Index: 17
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Introduction In cancer patients, current guidance suggests similar treatment for incidental and symptomatic venous thromboembolism (VTE), mainly based on retrospective data. We aimed to evaluate anticoagulant therapy in cancer patients with incidental and symptomatic VTE. Methods The Hokusai VTE Cancer study was a randomised controlled trial comparing edoxaban with dalteparin for cancer-associated VTE. The primary outcome was the composite of first recurrent VTE or major bleeding. Secondary outc...
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IntroductionLow-molecular-weight heparins are the standard treatment for cancer-associated thrombosis. Recently, direct oral anticoagulants are a new option for thrombosis treatment; however, data supporting the use of direct oral anticoagulants for cancer-associated thrombosis are limited.ObjectivesThe primary objective of this study was to determine the rate of recurrent cancer-associated thrombosis and major bleeding within 6 months of starting either low-molecular-weight heparin or direct or...
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