To compare the clinical outcome after a first episode of VTE in patients with well-defined thrombophilia who have been identified and treated for a longer duration with anticoagulants with patients with VTE who have not been routinely tested.
ID
Source
Brief title
Condition
- Chromosomal abnormalities, gene alterations and gene variants
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
The primary efficacy outcome consists of:
*recurrent VTE 18 months after the acute episode of VTE.
Secondary outcome
Secondary efficacy outcomes are:
* recurrent VTE at the end of the study.
* a composite endpoint of recurrent VTE and bleeding at the end of the study
* quality of life
* costs of testing and subsequent predefined prolongation of anticoagulant
therapy
Background summary
The last two decades genetic epidemiological studies have identified several
hereditary risk factors associated with venous thromboembolism (VTE), often
interacting with classical environmental risk factors. In 50-60% of patients
with a first episode of VTE such a thrombophilic defect can be detected in
blood. This has resulted in widespread testing, also in patients with a first
episode, but whether this is effective is unknown. One of the potential
implications of detecting thrombophilia would be to prolong the duration of
anticoagulant treatment after the acute episode of VTE, as is suggested in for
instance the guidelines of the American College of Chest Physicians 2004 (grade
2 level of evidence). Whether this is justified is intensely debated and
depends on the balance between potentially beneficial and harmful effects,
besides costs.
Study objective
To compare the clinical outcome after a first episode of VTE in patients with
well-defined thrombophilia who have been identified and treated for a longer
duration with anticoagulants with patients with VTE who have not been routinely
tested.
Study design
A randomized controlled trial of testing and no testing for thrombophilia in
patients with a first episode of VTE will be performed. Subsequent additional
anticoagulant treatment for a predefined period will be installed in those in
whom thrombophilia is detected in the testing group, while others will receive
a standard predefined duration of treatment. In addition, the impact on quality
of life of thrombophilia testing will be measured. Efficacy and safety outcomes
are risk for recurrent VTE and clinically important bleeding (also as a
composite outcome). Other outcomes are overall quality of life and costs
associated with the outcome measures 18 months after the initial episode of
VTE. Outcomes will be compared between thrombophilic patients allocated to the
testing group and to the no testing group. A total of 1336 patients will have
to be included to detect a benefit of 90% by prolonging anticoagulant treatment
in patients with thrombophilia while on treatment, and no reduction in the 6
months after cessation of treatment (overall RRR 55%) [power 80%, confidence
level 95%].
Intervention
Randomization into a testing and a non-testing group.
In the testing group, anticoagulant treatment will be prolonged (doubled in
duration) in those who tested positive for thrombophilia.
Study burden and risks
Patients will undergo 2 additional venapunctures for thrombophilia tests and
other predictive coagulation parameters.
Patients will be asked to fill out 3 quality of life questionnaires, 3 times;
each will take approximately 30 minutes to fill out.
The results of this study will answer the dilemma whether testing for
thrombophilia is beneficial (endpoints recurrent VTE after prolonged
anticoagulation) or is outweighed by an increase in bleeding and/or diminished
quality of life (besides costs).
Meibergdreef 9
1105 AZ AMSTERDAM
NL
Meibergdreef 9
1105 AZ AMSTERDAM
NL
Listed location countries
Age
Inclusion criteria
1) Subjects must be willing and able to give written informed consent
2) Confirmed symptomatic DVT, i.e., proximal vein or extensive calf-vein
thrombosis, involving at least the upper third part of the deep calf veins (trifurcation, AND/OR confirmed symptomatic PE, no longer than 2 months prior to randomization
3) age 18 years or older
Exclusion criteria
1. Previous episodes of DVT or PE
2. Active bleeding or high risk for bleeding contraindicating treatment with LMWH, fondaparinux or VKA
3. Insertion of a caval filter to treat the episode of VTE
4. Active cancer or anti-cancer treatment in the 6 months prior to the acute episode of VTE
5. Life expectancy < 18 months
6. Arterial thrombotic events in the context of a confirmed antiphospholipid antibody syndrome
7. Indications for VKA other than DVT
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EudraCT | EUCTR2006-004199-11-NL |
| CCMO | NL13891.018.06 |