Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

Prof David Fitzmaurice

ORCID ID

Contact details

Primary Care Clinical Sciences
The University of Birmingham
Edgbaston
Birmingham
B15 2TT
United Kingdom

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 measures

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

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 d–dimer 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

http://www.bham.ac.uk/

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

Results - basic reporting

Publication summary

2013 protocol in http://www.ncbi.nlm.nih.gov/pubmed/23497371

Publication citations

  1. 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.

Editorial Notes