Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
1
Study information
Scientific title
Extended anticoagulation treatment for venous thromboembolism (VTE): a prospective multicentre randomised controlled trial
Acronym
ExACT
Study hypothesis
This study will primarily investigate the role of extending treatment with oral anticoagulation for those patients with raised d-dimer levels prior to discontinuing treatment and will study the impact of this management on both recurrence of thrombosis and development of post-thrombotic syndrome.
Ethics approval
Not provided at time of registration
Study design
Prospective multicentre randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
GP practices
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Venous thromboembolism (VTE)
Intervention
Patients will be randomly allocated to either continue warfarin (Group W) for a further 2 years or to discontinue treatment (Group O).
Visit 1:
Patients will be interviewed and their medical notes reviewed. Data collected will be:
1. Concomitant medications
2. Smoking status
3. Alcohol consumption
4. Medical history
5. Body mass index (BMI)
6. INR data (therapeutic control in terms of percentage time in range from the start of their treatment)
7. 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) and then sent to a central laboratory to be frozen and stored for d dimer testing at the end of the study.
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 score as well as EQ 5D which allows the measurement of broad aspects of quality of life.
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 3 - 7:
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).
All patients will be asked to complete the VEINES-QOL/Sym a validated disease specific, quality of life score, and EQ 5D, questionnaires at the start of the study and at the 6 monthly reviews.
If a patient in Group O (off warfarin) has their warfarin restarted by their GP during the study period, the patient will be removed from the study.
The total duration of treatment and follow-up in all arms of the trial is 2 years.
Intervention type
Drug
Phase
Not Applicable
Drug names
Oral anticoagulation
Primary outcome measure
Number of recurrent thrombotic events between those showing a positive d-dimer on treatment and those showing a positive d-dimer who receive no treatment, measured every 6 months for 2 years.
Secondary outcome measures
Measured every 6 months for 2 years:
1. Severity of PTS between groups
2. Bleeding events
3. INR control in terms of percentage time in range
4. Optimal cut off on a d-dimer result -
5. Costs of d-dimer and subsequent extended treatment with anticoagulation
6. Cost effectiveness
7. Information on the types of patient who potentially benefit from extended warfarin treatment, age and gender
8. Patient quality of life
Overall trial start date
30/09/2010
Overall trial end date
30/09/2015
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Aged 18 years or over, either sex
2. Diagnosis of first unprovoked proximal deep vein thrombosis (DVT) or pulmonary embolism (PE)
3. On treatment with anticoagulants
4. Have completed 3 - 6 months of anticoagulant therapy (target 2 - 3)
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
352
Participant exclusion criteria
1. Patients under the age of 18 years
2. Patients with another indication for long term warfarin therapy, e.g., atrial fibrillation
3. Patients with a diagnosis of first unprovoked proximal DVT or PE who are no longer on anticoagulation therapy
4. Patients with a high risk of bleeding as evidenced by any of the following:
4.1. Patients with a previous episode of major bleeding where the cause was not effectively treated
4.2. Known thrombocytopaenia with a platelet count of less than 120 x 10^9 /L
4.3. Known chronic renal failure with a creatinine of more than 150 umols/L (1.7 mg/dl) or estimated glomerular filtration rate (eGFR) less than 30
4.4. Known chronic liver disease with a total bilirubin of more than 25 umols/L (1.5 mg/dl)
4.5. Active peptic ulcer
4.6. Poor compliance with, or control of, anticoagulation therapy during initial treatment (International Normalised Ratio [INR] control less than 50% time in range)
4.7. Patients requiring dual antiplatelet therapy (e.g., aspirin and clopidrogel)
5. Patients with a vena cava filter in place
6. Patients who have had a ddimer test performed within 2 months of potential enrolment other than for evaluation for suspected recurrent VTE that was not confirmed
7. Patients whose GP expects their life expectancy to be less than 5 years
8. Patients unable to attend follow up visits due to geographic inaccessibility
9. Patients participating in a competing investigation
10. Patients with known antiphospholipid syndrome or known deficiency
11. Patients with a diagnosis of active cancer
12. Patients unwilling to give consent
Recruitment start date
30/09/2010
Recruitment end date
30/09/2015
Locations
Countries of recruitment
United Kingdom
Trial participating centre
Primary Care Clinical Sciences
Birmingham
B15 2TT
United Kingdom
Sponsor information
Organisation
University of Birmingham (UK)
Sponsor details
c/o Brendan Laverty
Edgbaston
Birmingham
B15 2TT
United Kingdom
Sponsor type
University/education
Website
Funders
Funder type
Government
Funder name
National Institute for Health Research (NIHR) (UK) - Programme Grant for Applied Research (PGfAR) (ref: RP-PG-0608-10073)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
2013 protocol in http://www.ncbi.nlm.nih.gov/pubmed/23497371
Publication citations
-
Protocol
Tullett J, Murray E, Nichols L, Holder R, Lester W, Rose P, Hobbs FD, Fitzmaurice D, 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)., BMC Cardiovasc Disord, 2013, 13, 16, doi: 10.1186/1471-2261-13-16.