Clinical Trials Logo

Clinical Trial Details — Status: Recruiting

Administrative data

NCT number NCT02384135
Other study ID # 14-191
Secondary ID
Status Recruiting
Phase N/A
First received
Last updated
Start date March 2015
Est. completion date October 2019

Study information

Verified date September 2018
Source University Hospital, Geneva
Contact Marc Righini, MD
Phone +41 22 372 92 94
Email marc.righini@hcuge.ch
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial Summary

Prospective validation of an age-adjusted D-dimer cut-off to rule out deep vein thrombosis (DVT)


Description:

Suspected deep vein thrombosis (DVT) is a frequent clinical problem and remains a diagnostic challenge. The diagnostic approach of DVT relies on sequential diagnostic tests, such as the assessment of clinical probability, plasma D-dimer measurement, and compression ultrasonography (CUS).

Clinical probability has a fair predictive accuracy either evaluated implicitly or by clinical prediction rules and is useful for identifying patients with a low prevalence of DVT who can be usually fully investigated by non invasive tests.

The D-dimer test has been extensively evaluated in the exclusion of DVT, 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 DVT in outcome studies. The clinical usefulness of D-dimer is defined by the proportion of patients in whom DVT 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%.3 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, 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 both DVT and pulmonary embolism (PE) in older patients. For example, 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. In this study, raising the cutoff value to various points between 600 microg/L and 1000 microg/L 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 cutoff adjusted to age in a wide sample of 1712 patients with suspected PE. This "new" cutoff 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 500 microg/L, 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. Using the conventional cutoff, the VIDAS® D-Dimer test was negative (below 500 microg/L) 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 microg/L), 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%).

In a recently published a prospective outcome validation study of the age-adjusted cutoff in patients with a clinically suspected PE.13 The study included more than 3300 patients with suspected PE and showed that the three-month thromboembolic risk in patients with an nonhigh (or unlikely) clinical probability and a D-Dimer level between 500 microg/L and the age-adjusted cutoff was of 0.3% (95% CI: 0.1 5 to 1.7%). These results were in line with the one found in patients with a D-dimer level below the usual cutoff of 500 microg/L: 0.1% (95% CI: 0.0% to 0.7%). Moreover, in patients above 75 years the age-adjusted cutoff allowed to increase five-fold the number of patients in whom PE could be excluded without imaging test.

As PE and DVT are often considered as a similar disease, the investigators plan a prospective outcome study in which this progressive or "new" cutoff (age X 10 µg/L) will be used in patients with suspected DVT. In this multicentre study, clinical probability will be assessed by the Wells score (Table 1) and an ELISA D-dimer test (Vidas D-dimer Exclusion® test (Biomérieux, Marcy l'Etoile, Paris, France) or an immuno-turbidimetric test Innovance D-dimer (Siemens, Munich, Germany) will be performed. Patients with a nonhigh or "unlikely" clinical probability with the Wells score and a normal "new" D-dimer cutoff will be considered as not having DVT, 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 a D-dimer measurement above the age-adjusted cutoff will be investigated with CUS as currently admitted.


Recruitment information / eligibility

Status Recruiting
Enrollment 3300
Est. completion date October 2019
Est. primary completion date August 2019
Accepts healthy volunteers No
Gender All
Age group 18 Years and older
Eligibility Inclusion Criteria:

- All outpatients admitted to the emergency ward for suspected DVT 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:

- DVT suspicion raised more than 48 hours after admission to the hospital

- Pregnancy.

- Patients anticoagulated for a disease other than venous thromboembolism (for instance, atrial fibrillation)

- Concommitant PE suspicion

- Life expectancy less than 3 months

- Absence of informed consent

- Incapacity to deliver informed consent

Study Design


Related Conditions & MeSH terms


Intervention

Other:
Three-month thromboembolic risk in patient with D-dimer levels between the usual cut-off and the age-adjusted cut-off


Locations

Country Name City State
Canada Foothills Medical Centre Calgary Calgary/Alberta
Canada Hamilton General Hospital Hamilton Ontario
Canada Kingston General Hospital Kingston, Ontario
Canada Hôpital Monfort Monfort Ontario
Canada Hopital Maisonneuve-Rosemont Montreal Quebec
Canada Jewish General Hospital Montreal Quebec
Canada The Ottawa Hospital Ottawa
Canada Royal University Hospital Saskatoon Saskatchewan
Canada Thunder Bay regional Health Sciences center Thunder Bay, Ontario
Canada University Health network Toronto, Ontario
Canada Providence Health Care Vancouver Vancouver/British Columbia
France Grégoire LE GAL Brest
Switzerland Geneva University Hospital Geneva
Switzerland Marc Righini Geneva
Switzerland University Hospital of Geneva Geneva

Sponsors (3)

Lead Sponsor Collaborator
University Hospital, Geneva The Ottawa Hospital, University Medical Center Groningen

Countries where clinical trial is conducted

Canada,  France,  Switzerland, 

Outcome

Type Measure Description Time frame Safety issue
Primary Three-month thromboembolic risk in patient with D-dimer levels between the usual cut-off and the age-adjusted cut-off three-month follow-up
See also
  Status Clinical Trial Phase
Recruiting NCT05003843 - BOLT: Study of the Indigo® Aspiration System When Used in Patients With Deep Vein Thrombosis N/A
Recruiting NCT03937947 - Traumatic Brain Injury Associated Radiological DVT Incidence and Significance Study
Withdrawn NCT04136561 - Novel Strategy to Encourage Early Removal of Central Venous Catheters N/A
Completed NCT03420625 - Blood Flow Stimulation in the Lower Limbs by Application of Different External Devices N/A
Recruiting NCT02507180 - Safely Ruling Out Deep Vein Thrombosis in Pregnancy With the LEFt Clinical Decision Rule and D-Dimer
Completed NCT02555111 - Xarelto Versus no Treatment for the Prevention of Recurrent Thrombosis in Patients With Chronic Portal Vein Thrombosis. Phase 3
Terminated NCT02469376 - Evaluation of a New Imagingtechnologie for Thrombosis Phase 1
Completed NCT01975090 - The SENTRY Clinical Study N/A
Completed NCT02037607 - Incidence of Venous Thromboembolism in Children Undergoing Elective Neurosurgical Procedures N/A
Not yet recruiting NCT01357941 - Need for Antepartum Thromboprophylaxis in Pregnant Women With One Prior Episode of Venous Thromboembolism (VTE) N/A
Completed NCT00773448 - Screening for Occult Malignancy in Patients With Idiopathic Venous Thromboembolism N/A
Completed NCT00771303 - Ruling Out Pulmonary Embolism During Pregnancy:a Multicenter Outcome Study
Completed NCT00720915 - D-dimer to Select Patients With First Unprovoked Venous Thromboembolism Who Can Have Anticoagulants Stopped at 3 Months N/A
Completed NCT00244725 - Odiparcil For The Prevention Of Venous Thromboembolism Phase 2
Completed NCT00264277 - D-dimer to Establish Duration of Anticoagulation After Venous Thromboembolism Phase 4
Completed NCT00365950 - 3 Months' Versus 6 Months' Anticoagulation in Patients With DVT and/or PE Phase 4
Completed NCT00182403 - Fixed Dose Heparin Study Phase 3
Completed NCT03682419 - Evaluation of Precision and Accuracy of INR Measurements in a Point of Care Device (OPTIMAL) N/A
Not yet recruiting NCT04981327 - The API-CALF Study: Apixaban to Treat Calf Vein Thrombosis Phase 3
Recruiting NCT03240120 - A Study of Dabigatran Etexilate as Primary Treatment of Malignancy Associated Venous Thromboembolism Phase 3