Long-term treatment for cancer patients with deep vein thrombosis or pulmonary embolism - A randomized controlled trial

Background: Patients with cancer and a first venous thromboembolic event (VTE), who have been treated with molecular weight heparin (LMWH) for 6 months, usually continue anticoagulant treatment in case of active disease (metastatic cancer and/or ongoing cancer treatment). However, it is unknown whether LMWH or vitamin K antagonists (VKA) should be used for the long-term treatment. Aim: The aim of this study is to determine whether LMWH (Enoxaparin, Dalteparin, Nadroparin, Tinzaparin) is superior to VKA (Acenocoumarol, Phenprocoumon or Warfarin) for the long-term treatment of cancer patients who have completed 6-12 months of anticoagulation for VTE. Design: Multicenter, multinational, randomized, open label trial. Patients: Cancer patients who have received 6-12 months of anticoagulation for VTE will be randomly assigned to 6 additional months of LMWH or VKA (target INR 2.0-3.0). Allocation to treatment will be done centrally by block randomisation via a web-based system (concealed allocation) and will be stratified by center. The primary efficacy outcome is symptomatic recurrent VTE, i.e. deep vein thrombosis and pulmonary embolism. The primary safety outcome is major bleeding. Organization: A total of 65 to 87 recurrent VTE events are needed to show a 50% reduction with LMWH as compared to VKA (type I error 0.05, two-sided, power respectively 80 and 90%). To observe 75 events, with a 10% event rate per half year in the VKA arm and 5% in the LMWH arm a total of 1,000 patients will need to be included. Outcomes will be adjudicated by a central adjudication committee. A steering committee will be formed, preferably consisting of one member of every participating center. An electronic case report form will be used for data collection. (www.examinethrombosis.com)