title: Trial Protocol: a randomised controlled trial of extended anticoagulation treatment versus routine anticoagulation treatment for the prevention of recurrent VTE and post thrombotic syndrome in patients being treated for a first episode of unprovoked VTE (The ExACT Study).
abstract: BACKGROUND
  Venous thromboembolism comprising pulmonary embolism and deep vein thrombosis is a common condition with an incidence of approximately 1 per 1,000 per annum causing both mortality and serious morbidity. The principal aim of treatment of a venous thromboembolism with heparin and warfarin is to prevent extension or recurrence of clot. However, the recurrence rate following a deep vein thrombosis remains approximately 10% per annum following treatment cessation irrespective of the duration of anticoagulation therapy. Patients with raised D-dimer levels after discontinuing oral anticoagulation treatment have also been shown to be at high risk of recurrence.Post thrombotic syndrome is a complication of a deep vein thrombosis which can lead to chronic venous insufficiency and ulceration. It has a cumulative incidence after 2 years of around 25% and it has been suggested that extended oral anticoagulation should be investigated as a possible preventative measure.
  
  
  METHODS
  Patients with a first idiopathic venous thromboembolism will be recruited through anticoagulation clinics and randomly allocated to either continuing or discontinuing warfarin treatment for a further 2 years and followed up on a six monthly basis. At each visit D-dimer levels will be measured using a Roche Cobas h 232 POC device. In addition a venous sample will be taken for laboratory D-dimer analysis at the end of the study. Patients will be examined for signs and symptoms of PTS using the Villalta scale and complete VEINES and EQ5D quality of life questionnaires.
  
  
  CONCLUSIONS
  The primary aim of the study is to investigate whether extending oral anticoagulation treatment (prior to discontinuing treatment) beyond 3-6 months for patients with a first unprovoked proximal deep vein thrombosis or pulmonary embolism prevents recurrence. The study will also determine the role of extending anticoagulation for patients with elevated D-dimer levels prior to discontinuing treatment and identify the potential of D-dimer point of care testing for identification of high risk patients within a primary care setting.
  
  
  BACKGROUND
  ISRCTN73819751.
authors.affiliation: Primary Care Clinical Sciences, School of Health and Population Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.
authors.forename: Jayne
authors.initials: J
authors.lastname: Tullett
authors.forename: Ellen
authors.initials: E
authors.lastname: Murray
authors.forename: Linda
authors.initials: L
authors.lastname: Nichols
authors.forename: Roger
authors.initials: R
authors.lastname: Holder
authors.forename: Will
authors.initials: W
authors.lastname: Lester
authors.forename: Peter
authors.initials: P
authors.lastname: Rose
authors.forename: F D Richard
authors.initials: FD
authors.lastname: Hobbs
authors.forename: David
authors.initials: D
authors.lastname: Fitzmaurice
mesh_terms: D000284:Administration, Oral; D000925:Anticoagulants / Q000008:administration & dosage*; D015415:Biomarkers / Q000097:blood; D002985:Clinical Protocols; D004334:Drug Administration Schedule; D004739:England; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006801:Humans; D054070:Postthrombotic Syndrome / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D011320:Primary Health Care; D011788:Quality of Life; D012107:Research Design; D055502:Secondary Prevention; D011795:Surveys and Questionnaires; D013997:Time Factors; D016896:Treatment Outcome; D054556:Venous Thromboembolism / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000517:prevention & control*; D014859:Warfarin / Q000008:administration & dosage*
chemical_list: D000925:Anticoagulants; D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; C036309:fibrin fragment D; D014859:Warfarin