The primary objective of this study is to perform a clinical and analytical validation of novel point-of-care (POC) D-dimer assays, in particular regarding their ability to rule-out VTE using an age-adjusted D-dimer cut-of. Secondary objectives are…
ID
Source
Brief title
Condition
- Embolism and thrombosis
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
For our primary objective, we will quantify the diagnostic power to (safely)
rule out VTE by calculating the failure rate, plus corresponding 95% CI (using
Fischer*s exact test) of each POC D-dimer assay, both for using a fixed cut-of
value of 500 ng/ml and for using an age-dependent cut-off. The failure rate is
defined as the proportion of patients diagnosed with VTE during 3 months of
follow-up in those with D-dimer below the chosen threshold in our study
patients (i.e. those with a low score on the CDR).
Secondary outcome
The added diagnostic information from inflammatory or coagulation biomarkers
will be quantified by using multivariable logistic regression analysis, with
VTE presence as the binary outcome of the model. Various logistic models will
be constructed. In a first basic model, (inflammatory - CRP, procalcitonin
and/or coagulation - TAT) biomarkers will be added to a model including all
items from the CDR plus the results from D-dimer testing. Next, this model will
be expanded using interaction terms for biomarker results with D-dimer testing,
CDR score, gender and/or age. Biomarker results will be added as continuous
variables, after checking linearity assumptions.
In a limited number of study patients (100 of 750 EVA patients) a POC
measurement is done in the GP's office with blood of a vingerprick additional
to the venapuncture in the laboratory.
Background summary
Venous thrombo-embolism (VTE), i.e. deep vein thrombosis (DVT) or pulmonary
embolism (PE), poses a major diagnostic challenge for the general practitioner
(GP) because signs and symptoms can be non-specific and even often quite
minimal. The diagnostic work-up starts with scoring a clinical decision rule
(CDR). If the CDR yields a low score (low VTE probability) a negative D-dimer
test result can safely rule-out VTE without referral for imaging. This approach
has been validated for use in primary care and is currently recommended in
clinical guidelines.
However, the usability of this diagnostic approach is hampered in two clinical
situations. First, D-dimer levels increase with increasing age and recently an
age adjusted cut-off level for D-dimer test results was proposed to increase
the diagnostic yield of D-dimer (i.e. better rule-out VTE) in elderly
patients. Second, the most important differential diagnosis of VTE is a lung-
(in the case of a primary suspicion of PE) or skin (in the case of a primary
suspicion of DVT) infection. In these cases, due to inflammation, D-dimer
levels are also increased, in the absence of VTE, again decreasing the
diagnostic yield of D-dimer.
Therefore, in this study, we want to validate novel quantitative point-of-care
D-dimer tests, in particular regarding their use of the age-adjusted cut-off
value. In addition, we want to quantify the added diagnostic information
obtained from inflammatory and coagulation biomarkers in patients suspected of
VTE in primary care.
Study objective
The primary objective of this study is to perform a clinical and analytical
validation of novel point-of-care (POC) D-dimer assays, in particular regarding
their ability to rule-out VTE using an age-adjusted D-dimer cut-of. Secondary
objectives are evaluating the added diagnostic information as obtained from
inflammatory biomarkers. Finally, we want to evaluate a novel biomarker for
coagulation that has recently been developed (e.g. thrombin-anti-thrombin
complex; TAT). The diagnostic yield of TAT has never been tested in a clinical
population of patients suspected of VTE in primary care.
Study design
Prospective cohort study with 3 months of follow-up in patients suspected of
VTE in a primary care setting, in whom the general practitioner (GP) considers
ruling-out VTE.
Study burden and risks
There will be sampling of capillairy blood with a vingerprick (20 mul). This
can be painfull. The risk is very low.
Universiteitsweg 100
Utrecht 3584CG
NL
Universiteitsweg 100
Utrecht 3584CG
NL
Listed location countries
Age
Inclusion criteria
Patients are eligible for the study if:
- The general practitioner (GP) has a suspicion of deep venous thrombosis (DVT) or pulmonary embolism (PE), i.e. unexplained pain, swelling, and/or redness of the leg in case of DVT, or unexplained shortness of breath and pain when breathing in case of PE.
- Patients have a low score on a clinical decision rule (low pre-test probability of DVT or PE), and thus the GP aims to rule-out VTE (if possible) using routine care D-dimer testing.
Exclusion criteria
Exclusion criteria are:
- Age below 18.
- Already using anticoagulant treatment with vitamin K antagonists, Non vitamin K Oral Anti Coagulants (NOAC) and/or low molecular-weight heparin (LMWH).
- With a non-low score on a clinical decision rule
- With an already determined POC D-dimer by the GP, suitable for risk stratification
- Life expectancy less than 3 months.
- Unwilling to participate with this study (opt-out procedure).
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
In other registers
| Register | ID |
|---|---|
| CCMO | NL56475.041.16 |
| OMON | NL-OMON29132 |