D-dimer Testing Tailored to Clinical Pretest Probability in Suspected Pulmonary Embolism

Study Overview
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Brief Summary
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Prospective, multicentre, cohort study assessing a diagnostic management strategy for suspected Pulmonary Embolism with independent central adjudication of outcomes

Detailed Description
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This is a prospective, multi-centre, cohort study that will assess a new diagnostic management strategy for suspected Pulmonary Embolism (inpatients and outpatients). The new diagnostic strategy is designed to reduce the use of imaging tests for Pulmonary Embolism, particularly Computed Tomography Pulmonary Angiogram, by excluding Pulmonary Embolism with combinations of Clinical Pretest Probability and D-dimer results in a higher proportion of patients. 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 of 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.

Official Title
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D-dimer Testing,Tailored to Clinical Pretest Probability to Reduce the Use of CT Pulmonary Angiography in Suspected Pulmonary Embolism: A Management Study (The Pulmonary Embolism Graduated D-dimer [PEGeD] Study)

Conditions
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Pulmonary Embolism

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients (either outpatients or inpatients) with clinically suspected Pulmonary Embolism. Exclusion Criteria: Age less than 18 years. Treated with full-dose anticoagulation for ≥ 24 hours before D-dimer was measured. Major surgery (general or spinal anesthesia) in the past 21 days. Result of the D-dimer assay that will be used to manage the patient in the study is known before Clinical Pretest Probability was done. Computed Tomography Pulmonary Angiogram or Ventilation Perfusion Scan was performed: before Clinical Pretest Probability was documented, or in a patient with Low Clinical Pretest Probability and a D-dimer level <1,000 ug/L (or equivalent), or in a patient with Moderate Clinical Pretest Probability and a D-dimer level <500 ug/L (or equivalent). Computed Tomography of the chest with contrast will be performed for another reason (e.g. to assess for malignant disease or aortic dissection), and would be performed even if Pulmonary Embolism is excluded by Clinical Pretest Probability and D-dimer testing. Ongoing need for anticoagulant therapy. Life expectancy less than 3 months. Geographic inaccessibility which precludes follow-up. Known pregnancy. Inability to provide informed consent.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No CT Pulmonary Angiography<br>Low Clinical Pretest Probability with D-dimer < 1000 ug/L and Moderate Clinical Pretest Probability with D-dimer < 500ug/L | |
| CT Pulmonary Angiography Required<br>Low Clinical Pretest Probability with D-dimer > or = 1000ug/L and Moderate Clinical Pretest Probability with D-dimer > or = 500 ug/L and High Clinical Pretest Probability | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with confirmed symptomatic proximal Deep Vein Thrombosis or Pulmonary Embolism | Proximal Deep Vein Thrombosis includes thrombosis confined to the calf vein trifurcation but not isolated more distal Deep Vein Thrombosis. Pulmonary Embolism does not include isolated sub-segmental abnormalities on Computed Tomography Pulmonary Angiography. | 90 Days (+ or - 7days) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with bleeding | Major and minor bleeding | 90 days (+ or - 7days) | 
| Number of patient Deaths | All deaths and cause specific deaths | 90 days (+ or - 7days) | 
| Number of patients with Venous Thromboembolism | Venous Thromboembolism, including events that do not satisfy the primary outcome (e.g. isolated distal Deep Vein Thrombosis or subsegmental Pulmonary Embolism) but that are confirmed by the adjudication committee. | 90 days (+ or - 7days) |