Pulmonary Embolism Clinical Trial
— ADJUSTOfficial title:
Age-adjusted D-dimer Cut-off Levels to Rule Out Pulmonary Embolism: a Prospective Outcome Study.
Verified date | April 2013 |
Source | University Hospital, Geneva |
Contact | n/a |
Is FDA regulated | No |
Health authority | Switzerland: Ethikkommission |
Study type | Interventional |
Suspected pulmonary embolism (PE) is a frequent clinical problem and remains a diagnostic
challenge. The diagnostic approach of PE relies on sequential diagnostic tests, such as
plasma D-dimer measurement, multi-slice computed tomography (MSCT) and pulmonary
angiography. In addition, the diagnostic workup is usually stratified according to the
clinical probability of pulmonary embolism. Clinical probability has a fair predictive
accuracy either evaluated implicitly or by clinical prediction rules1 and is useful for
identifying patients with a low prevalence of pulmonary embolism who can be usually fully
investigated by non invasive tests.The D-dimer test has been extensively evaluated in the
exclusion of pulmonary embolism, particularly in outpatients. ELISA D-dimer and
second-generation latex agglutination (immuno-turbidimetric tests) have a remarkably high
sensitivity and have been proved safe first-line tests in association with clinical
probability to rule out pulmonary embolism in outcome studies. The clinical usefulness of
D-dimer is defined by the proportion of patients in whom pulmonary embolism may be ruled out
by a normal result and it is determined by the specificity. However, ELISA and
second-generation latex agglutination (immuno-turbidimetric tests) tests have a quite
limited overall specificity of around 35% to 40%. Therefore, many investigators tried to
increase the D-dimer thresholds in particular in elderly patients to increase the rate of
patients in whom the diagnosis could be excluded by this easy and inexpensive test. Several
studies have shown that D-dimer levels increase with age and which turns in a decreased
specificity of the D-dimer test at the usual threshold in the elderly, and thus to a less
useful test to exclude PE in older patients. Indeed, ELISA D-dimer is able to rule out PE in
60% of patients aged less than 40 years, but in only 5% of patients above the age of 80.8 In
this study, raising the cut-off value to various points between 600 ng/ml and 1000 ng/ml
increased specificity, but this came at the cost of safety with more false negative test
results. In this analysis, however, no stratification was made for clinical probability and
the sample was small.
Recently, the investigators retrospectively assessed the value of a progressive cut-off
adjusted to age in a wide sample of 1712 patients. This "new" cut-off was defined for
D-Dimer test positivity in each patient by multiplying patient's age by 10. All patients
with a D-Dimer level below 500mg/ml, and all patients above 50 years whose D-Dimer levels
were inferior to their age multiplied by 10 were considered as having a negative D-Dimer
test. The exact derivation and validation of this "new" D-dimer cut-off is described
hereafter. Using the conventional cutoff, the VIDAS® D-Dimer test was negative (below 500
mg/ml) in 512/1712 patients (29.9%) and none had PE during initial workup or the three-month
follow-up period.
Using the cutoff adjusted to age (cutoff for D-Dimer test positivity equals age multiplied
by ten, in mg/ml), the figure was as follows. D-Dimer levels were below the adjusted cutoff
in 615/1712 patients (35.9%, number needed to test 2.8). This represented a statistically
significant 20.1% increase in the number of patients in whom the D-Dimer test was considered
as negative, p=0.0002. Of these 615 patients, 5 had PE during initial workup (0.8%, 95
percent confidence interval 0.4 to 1.9%).
These data suggest that adopting this progressive cut-off in patients above 50 years, could
increase of about 20% the number of patients in whom PE could be excluded without further
testing, with an acceptable safety profile as the three-month thromboembolic rate remained
very low.
Therefore, the investigators plan a prospective outcome study in which this progressive or
"new" cut-off (age X 10 ng/ml) in patients above 50 years will be used. In this multicentre
study, clinical probability will be assessed by the simplified revised Geneva revised score
(Table 1) and an ELISA D-dimer test will be performed [Vidas D-Dimer Exclusion® test
(Biomérieux, Marcy l'Etoile, Paris, France)]. Patients with a non high clinical probability
with the simplified revised Geneva score and a normal "new" D-dimer cut-off with the Vidas
D-dimer Exclusion®, (Biomerieux, Marcy l'Etoile, France) will be considered as not having
PE, and will be followed for three-months to assess possible VTE recurrences. The main
outcome will be the rate of thromboembolic events during a formal 3-month follow-up in
patients not anticoagulated on the basis of this strategy. Patients with positive D-dimers
will be investigated with MSCT as currently admitted.
Status | Completed |
Enrollment | 3306 |
Est. completion date | December 2013 |
Est. primary completion date | July 2013 |
Accepts healthy volunteers | No |
Gender | Both |
Age group | 18 Years and older |
Eligibility |
Inclusion Criteria: All outpatients admitted to the emergency ward for suspected pulmonary embolism defined as acute onset of new or worsening shortness of breath or chest pain without another obvious etiology will be included in the study, provided they correspond to the following diagnostic and exclusion criteria and they have signed an informed consent form. Exclusion Criteria: - PE suspicion raised more than 24 hours after admission to the hospital - Absence of informed consent - Incapacity to deliver informed consent - Life expectancy less than 3 months - Geographic inaccessibility for follow-up - Pregnancy. - Patients anticoagulated for a disease other than venous thromboembolism (for instance, atrial fibrillation) - Patients allergic to contrast medium - Impaired renal function (creatine clearance less than 30 ml/min as calculated by the Cockroft formula). |
Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Diagnostic
Country | Name | City | State |
---|---|---|---|
France | Angers University Hospital | Angers | |
France | Grégoire Le Gal | Brest | |
Netherlands | Amsterdam University hospital | Amsterdam | |
Switzerland | Geneva University Hospital | Geneva |
Lead Sponsor | Collaborator |
---|---|
Marc Righini | Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA), University Hospital, Angers, University Hospital, Brest |
France, Netherlands, Switzerland,
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | The main outcome is the rate of thromboembolic events during a formal 3-month follow-up in patients not anticoagulated on the basis of a PE ruled out by the association mentioned here above. | 3 months | Yes | |
Secondary | Prospective validation of the simplified revised Geneva score. | 3 years | Yes |
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