The Designer D-dimer Deep Vein Thrombosis Diagnosis (4D) Study (4D)

D-dimer Testing, Tailored to Clinical Pretest Probability, to Minimize Initial and Follow-up Ultrasound Imaging in Suspected Deep Vein Thrombosis: A Management Study

This is a cohort study that will assess a new diagnostic management strategy for suspected Deep Vein Thrombosis in outpatients.The new diagnostic strategy is designed to reduce the use of ultrasound testing on the day of presentation, and reduce repeat ultrasound testing a week after an initial normal test.

Study Overview

• Status: Completed
• Conditions: Suspected Deep Vein Thrombosis

Detailed Description

This is a prospective, multicentre, cohort study that will assess a new diagnostic management strategy for suspected Deep Vein Thrombosis in outpatients. The new diagnostic strategy is designed to reduce the use of ultrasound testing on the day of presentation, and reduce repeat ultrasound testing a week after an initial normal test. Less ultrasound testing will be performed because: i) more patients will have deep vein thrombosis excluded by combinations of Clinical Pretest Probability and D-dimer results on the day of presentation; and, ii) in those who still need an ultrasound, a repeat ultrasound a week after a normal result will only be performed if the D-dimer result is markedly abnormal at initial presentation. The safety of this management strategy will be established by demonstrating a very low rate of proximal Deep Vein Thrombosis or Pulmonary Embolism during 90 days follow-up in patients who had anticoagulant therapy withheld in response to negative diagnostic testing. Diagnostic test utilization will be assessed. All clinical outcomes will be adjudicated by a central independent adjudication committee that will be blind to initial D-dimer measurements and patient management.

• Study Type: Observational
• Enrollment (Actual): 1513

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada, T6G 2B7
      • University of Alberta Hospital
  • Nova Scotia
    • Halifax, Nova Scotia, Canada, B3H1V7
      • Nova Scotia Cancer Centre
  • Ontario
    • Hamilton, Ontario, Canada, L8N 4A6
      • St. Joseph's Healthcare
    • Hamilton, Ontario, Canada, L8L 2X2
      • Hamilton Health Sciences - Hamilton General
    • Hamilton, Ontario, Canada, L8N 3Z5
      • Hamilton Health Sciences - McMaster
    • Hamilton, Ontario, Canada, L8V1C3
      • Juravinski Cancer Hospital
    • London, Ontario, Canada, N6A 5W9
      • London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1H 8L6
      • The Ottawa Hospital Regional Centre
  • Quebec
    • Montreal, Quebec, Canada, H3T 1E2
      • The Jewish General Hospital
    • Sherbrooke, Quebec, Canada, J1G2EB
      • Centre Hospitalier Universitaire de Sherbrooke

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Male and females outpatients with a suspected Deep Vein Thrombosis

Description

Inclusion Criteria:

1) Consecutive outpatients (i.e. non-hospitalized patients) with clinically suspected Deep Vein Thrombosis.

Exclusion Criteria:

1. Age less than 18 years.
2. Treated with full-dose anticoagulation for ≥ 24 hours before D-dimer was measured.
3. D-dimer level known before Clinical Pretest Probability documented.
4. Ultrasound of the leg performed before Clinical Pretest Probability was documented
5. Ultrasound was or will be performed in a patient with low Clinical Pretest Probability and a d-dimer <1000(or equivalent), or with Moderate Clinical Pretest Probability and a D-dimer <500 (or equivalent) (e.g. suspected bleeding).
6. Ongoing need for anticoagulant therapy.
7. Suspected Pulmonary Embolism.
8. Superficial venous thrombosis that requires, or may require, anticoagulant therapy.
9. Life expectancy less than 3 months.
10. Previously confirmed episode of Deep Vein Thrombosis.
11. Geographic inaccessibility which precludes follow-up.
12. Known pregnancy.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
No Ultrasound; Low Clinical Pretest Probability and D-dimer < 1000 ug/L; Moderate Clinical Pretest Probability and D-dimer < 500 ug/L
Ultrasound Required; Low Clinical Pretest Probability and D-dimer 1000 - 3000 ug/L; Moderate Clinical Pretest Probability and D-dimer 500 - 3000 ug/L; High Clinical Pretest Probability

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Confirmed symptomatic proximal Deep Vein Thrombosis	The primary outcome is confirmed symptomatic proximal Deep Vein Thrombosis (including involvement of the calf vein trifurcation but not isolated more distal Deep Vein Thrombosis; or pulmonary embolism (not including isolated sub-segmental abnormalities on Computed Tomography Pulmonary Angiogram; within 90 days (± 7 days for follow-up assessment) that is not diagnosed by scheduled diagnostic testing (includes events that occur between initial and scheduled follow-up proximal ultrasound examinations).	within 90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical Pretest Probability/ D-dimer/ Compression Ultrasound subgroups	The primary outcome in the following subgroups: Low Clinical Pretest Probability and D-dimer <1000 ug/L; Moderate Clinical Pretest Probability and D-dimer <500 ug/L; Moderate Clinical Pretest Probability and D-dimer 500 -999 ug/L; High Clinical Pretest Probability and D-dimer <500 ug/L; Low Clinical Pretest Probability and D-dimer 1000-2999 ug/L and negative initial ultrasound; Moderate Clinical Pretest Probability and D-dimer 1000-2999 ug/L and negative initial ultrasound; High Clinical Pretest Probability and D-dimer 500-1499 ug/L and negative initial ultrasound	within 90 days
Death	Death within 90 days (± 7 days for follow-up assessment).	within 90 days

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: Canadian Institutes of Health Research (CIHR)
• Investigators: Study Director: Mark Levine, MD, ocog

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: February 1, 2014
• Primary Completion (ACTUAL): June 17, 2020
• Study Completion (ACTUAL): October 15, 2020

Study Registration Dates

• First Submitted: January 13, 2014
• First Submitted That Met QC Criteria: January 14, 2014
• First Posted (ESTIMATE): January 16, 2014

Study Record Updates

• Last Update Posted (ACTUAL): September 28, 2021
• Last Update Submitted That Met QC Criteria: September 27, 2021
• Last Verified: September 1, 2021

More Information

Terms related to this study

• Keywords: Deep Vein Thrombosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Venous Thrombosis
• Other Study ID Numbers: OCOG-2013-4D