- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02384135
Age-adjusted D-dimer Cutoff Levels to Rule Out Deep Vein Thrombosis: a Prospective Outcome Study (ADJUST-DVT)
Study Overview
Status
Conditions
Detailed 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.
Study Type
Enrollment (Anticipated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Marc Righini, MD
- Phone Number: +41 22 372 92 94
- Email: marc.righini@hcuge.ch
Study Contact Backup
- Name: Louise Riberdy, Nurse
- Phone Number: +41 22 372 92 92
- Email: louise.riberdy@hcuge.ch
Study Locations
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Kingston, Ontario, Canada
- Recruiting
- Kingston General Hospital
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Contact:
- Colin Bell, MD
- Email: colin.bell@queensu.ca
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Ottawa, Canada
- Recruiting
- The Ottawa Hospital
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Contact:
- Grégoire Le Gal, MD, PhD
- Email: glegal@toh.ca
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Thunder Bay, Ontario, Canada
- Not yet recruiting
- Thunder Bay Regional Health Sciences Center
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Contact:
- Meghan Garnett, MD
- Email: mgarnett@nosm.ca
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Toronto, Ontario, Canada
- Recruiting
- University Health Network
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Contact:
- Jennifer Hulme, MD
- Email: Jennifer.hulme@uhn.ca
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Calgary/Alberta
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Calgary, Calgary/Alberta, Canada
- Recruiting
- Foothills Medical Centre
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Contact:
- Eddy Lang, MD
- Email: Eddy.Lang@albertahealthservices.ca
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Ontario
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Hamilton, Ontario, Canada, L8L 2X2
- Recruiting
- Hamilton General Hospital
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Principal Investigator:
- Sam Schulman, MD
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Contact:
- Sam Schulman, MD
- Phone Number: 44479 905-527-0271
- Email: schulms@mcmaster.ca
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Monfort, Ontario, Canada
- Recruiting
- Hôpital Monfort
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Contact:
- Shaun Visser, MD
- Email: shaunvisser@monfort.on.ca
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Quebec
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Montreal, Quebec, Canada
- Recruiting
- Jewish General Hospital
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Principal Investigator:
- Susan Kahn, MD
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Contact:
- Susan Kahn, MD
- Phone Number: 4667 514-340-8222
- Email: susan.kahn@mcgill.ca
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Montreal, Quebec, Canada
- Recruiting
- Hopital Maisonneuve-Rosemont
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Contact:
- Jeannine Kassis, MD
- Email: jkassis@ssss.gouv.qc.ca
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Principal Investigator:
- Jeannine Kassis, MD
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Saskatchewan
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Saskatoon, Saskatchewan, Canada
- Recruiting
- Royal University Hospital
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Contact:
- Otto Moodley, MD
- Email: omoodley@saskcancer.ca
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Principal Investigator:
- Otto Moodley, MD
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Vancouver/British Columbia
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Vancouver, Vancouver/British Columbia, Canada
- Not yet recruiting
- Providence Health Care
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Contact:
- Robert Stenstrom, MD
- Email: Rob.Stenstrom@ubc.ca
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Brest, France, 29609
- Recruiting
- Grégoire Le Gal
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Contact:
- Grégoire LE GAL, PUPH
- Phone Number: +33 298347336
- Email: gregoire.legal@chu-brest.fr
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Geneva, Switzerland
- Recruiting
- University Hospital of Geneva
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Contact:
- Marc Righini, MD
- Phone Number: 0041 22 372 92 94
- Email: marc.righini@hcuge.ch
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Geneva, Switzerland, 1205
- Recruiting
- Marc Righini
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Contact:
- Marc Righini, MD
- Email: marc.righini@hcuge.ch
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Geneva, Switzerland, 1211
- Recruiting
- Geneva University Hospital
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Contact:
- Marc Righini, MD
- Phone Number: +41 22 372 92 94
- Email: marc.righini@hcuge.ch
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Contact:
- Louise Riberdy, Nurse
- Phone Number: +41 22 372 92 92
- Email: louise.riberdy@hcuge.ch
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Principal Investigator:
- Grégoire Le Gal, MD
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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 Plan
How is the study designed?
Design Details
- Primary Purpose: Diagnostic
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Other: interventional
Patients with D-dimer levels between the usual cutoff and the age-adjusted cutoff will be left untreated and followed-up for three months
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Three-month thromboembolic risk in patient with D-dimer levels between the usual cut-off and the age-adjusted cut-off
Time Frame: three-month follow-up
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three-month follow-up
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Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Grégoire Le Gal, MD, Ottawa University Hospital
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 14-191
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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