D-Dimer Guided Oral Anticoagulant Treatment (OAT)

Safety and Efficacy of a D-Dimer-Guided Strategy for Extension of Secondary Prophylaxis of Venous Thromboembolism - a Prospective and Randomized Management Trial

This clinical trial will investigate the hypothesis that D-Dimer testing can be successfully used to tailor the duration of OAT in patients after an unprovoked episode of deep venous thrombosis (DVT) using a prospective, randomized, and controlled design.

After a first episode of acute deep venous thrombosis (DVT) the risk of recurrence is relatively high and clinical consequences are important. Therefore, secondary prophylaxis using oral anticoagulant treatment (OAT) is usually established in these patients. This treatment very effectively reduces the risk of recurrences but induces an increased risk of bleeding. Major bleeding complications can be expected in ~2% patient-years. Therefore, current recommendations limit OAT to a period of 3 to 12 months. After stopping of OAT, however, ~10 % of patients with an initial episode of unprovoked DVT will develop a recurrent event within 1 year. This group of patients may benefit from prolonged OAT. The results of 2 independent observational studies showed a significantly higher risk of recurrence in patients showing increased levels of D-Dimer after withdrawal of OAT. D-Dimer is a biomarker that indicates fibrin formation followed by fibrinolysis. Based on these data we hypothesize that D-Dimer testing can be successfully used to tailor the duration of OAT in patients after an unprovoked episode of DVT. This clinical trial will investigate this hypothesis using a prospective, randomized, and controlled design.

Inclusion Criteria:

To be enrolled in this study, patients must:

• have an objectively confirmed first episode of unprovoked VTE or of VTE during a minor transient risk factor. Minor transient risk factors include 6 weeks of estrogen therapy, prolonged air travel (i.e., > 6 hours), pregnancy, less marked leg injuries or immobilization without injury or surgical intervention
• be scheduled to receive oral anticoagulant treatment for at least 3 months
• be willing to be randomized
• be willing to participate for the full duration of the study

Exclusion Criteria:

• pregnancy or breast feeding
• contraindications against OAT (i.e., intracranial hemorrhage, subarachnoid hemorrhage, hemorrhagic stroke)
• age < 18 years
• presence of antiphospholipid antibodies or any other thrombophilic risk factor requiring long-term OAT (i.e., antithrombin deficiency, hereditary PC deficiency)
• poor patient compliance