For participants

Here we provide information for trial partcipants on who can enter, and what happens during visits.

Who can enter?

Inclusion criteria

  • People aged 18 years or over with a diagnosis of first unprovoked proximal DVT or PE on treatment with anticoagulants
  • Patients who have completed a minimum of 3 months of anticoagulant therapy (target 2-3)

Exclusion criteria

  • Patients under the age of 18 years
  • Patients with another indication for long term warfarin therapy eg Atrial Fibrillation
  • Patients with a diagnosis of first unprovoked proximal DVT or PE who are no longer on anticoagulation therapy
  • Patients with a high risk of bleeding as evidenced by any of the following:
  • Patients with a previous episode of major bleeding where the cause was not effectively treated
  • Known thrombocytopenia with a platelet count of less than 120 x109 /L
  • Known chronic renal failure with a creatinine of more than 150 µmols/L (1.7mg/dl) or eGFR less than 30
  • Known chronic liver disease with a total bilirubin of more than 25µmols/L (1.5mg/dl)
  • Active peptic ulcer
  • Patients requiring antiplatelet therapy (eg Aspirin and/or Clopidogrel)
  • Patients with a vena cava filter in place
  • Patients who have had a D–dimer test performed within 2 months of potential enrolment other than for evaluation for suspected recurrent VTE that was not confirmed
  • Patients whose GP expects their life expectancy to be less than 5 years
  • Patients unable to attend follow up visits due to geographic inaccessibility
  • Patients participating in a competing investigation
  • Patients with known antiphospholipid syndrome
  • If patients are subsequently found to have antiphosphlipid syndrome then they will have to be excluded.
  • Patients with known inherited protein C and/or protein S or antithrombin deficiency
  • If patients are subsequently found to have protein C and/or protein S or anithrombin deficiency then they will have to be excluded.
  • Patients with a diagnosis of active cancer
  • Patients unwilling to give consent

Definition of unprovoked VTE

The episode will be defined as unprovoked as long as there is no history within the previous 3 months of:

major surgery; lower limb trauma e.g. fracture, cast, limping for 3 days; use of the combined oral contraceptive pill or hormone replacement therapy ; pregnancy; significant immobility e.g. confined to bed for 3 days; active cancer.

Definition of Proximal

Proximal refers to a DVT in the trifurcation area, popliteal, superficial femoral, deep femoral, common femoral and iliac veins.

Tests and treatments

Visit 1 (This is the same visit as the information, consent and randomisation visit and should be within 2 weeks before the end of current anticoagulation treatment)

Patients will be interviewed to collect the following data:

Concomitant medications; ethnicity; smoking status; alcohol consumption; medical history; BMI; and family history of VTE

A heparinised venous sample of blood will be taken for a D-dimer test on a point-of-care device (Cobas h 232, Roche diagnostics). In addition citrated venous samples will be collected for D-dimer testing and microparticle levels and EDTA samples for circulating endothelial cell levels. These will be sent to a central laboratories to be frozen and stored for analysis during and at the end of the study.

The D-dimer result will be recorded centrally onto a database for future analysis and both patient and researcher will be blinded as to the result of this test.

All patients will be clinically examined for signs and symptoms of post thrombotic syndrome (PTS) using a validated clinical scoring system (the Villalta scale) and will also complete the VEINES quality of life score25 as well as EQ 5D which allows the measurement of broad aspects of quality of life.26 In addition the patients will complete a costs questionnaire relating to the expenses incurred on a recent anticoagulation clinic visit. Where questionnaires are incomplete or unclear the patients will be contacted by telephone to clarify and complete the responses. ExACT Protocol Version 2.9 16

Compression stockings will be used by patients as advised by the clinician treating the DVT and the researchers will not influence their utilisation.

The anticoagulation clinic that the patient would normally attend will be informed that the patient is entering a study as will any specific hospital consultants who are involved with the patients? care (e.g. haematologists). Patients randomly allocated to Group W will be followed-up through their usual oral anticoagulation service provided in terms of warfarin management and the anticoagulation clinic lead will be asked to extend their clinic visits for a further 2 years. Patients randomly allocated at this point to Group O will undergo a further D-dimer test 1 month after cessation of treatment. Again both researcher and patient will be blinded to this result.

Visits 2-6  All patients randomised (Groups W and Group O) will be reviewed every 6 months for 2 years in total to assess evidence of VTE recurrence, clinical assessment of PTS, and measurement of D-dimer (again patient and researcher are blinded to these results). INR data and warfarin dosing history for the duration of the study will be collected at each follow up appointment.

All patients will again be asked to complete the VEINES-QOL/Sym a validated disease specific, quality of life score, and EQ 5D, questionnaires.

If a patient in Group O (off warfarin) has their warfarin restarted during the study period for a VTE recurrence then they will be removed from the study but a case review will be carried out in patient?s primary care notes looking for evidence of thrombotic events. If a patient in Group O has to restart warfarin for another reason e.g. atrial fibrillation, then they will continue to be followed up in the usual manner. If a patient in Group W (on warfarin) has to permanently stop taking their warfarin during the study then they will also be followed up and both groups will be included in the final analysis on an intention to treat basis. If a patient in Group W has a temporary break in their treatment for any reason, they will continue to follow the same visit regime, making a note of the temporary break.

Patients in Group W will be asked to return for a final D-dimer test 1 month after discontinuing warfarin.