D-Dimer Guided Oral Anticoagulant Treatment (OAT)

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Deep Venous Thrombosis

Intervention / Treatment
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* Drug: Phenprocoumon
* Drug: Warfarin-Natrium


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 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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Design Details

Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: oral anticoagulants<br>Experimental intervention: Extension of OAT in VTE patients showing high plasma levels of D-Dimer after end of routine secondary prophylaxis. | Drug: Phenprocoumon<br>* Phenprocoumon 3 mg, tablet, INR adjusted<br>Drug: Warfarin-Natrium<br>* Warfarin-Natrium 5 mg, tablet, INR adjusted<br>|
| No Intervention: 2<br>Control: Withdrawal of OAT in VTE patients after end of routine secondary prophylaxis and receiving low molecular weight heparin in risk situations. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of objectively documented deep vein thrombosis (DVT) and/or pulmonary embolism (PE) |  | Duration of intervention per patient (24 months) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence and severity of signs and symptoms associated with OAT-induced bleeding measured using the World Health Organization (WHO) bleeding scale. |  | Duration of intervention per patient (24 months) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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DVT, Venous thromboembolism, D-Dimer, thrombophilia, secondary prophylaxis, secondary prophylaxis using oral anticoagulant treatment (OAT), higher risk of recurrence in patients showing increased levels, of D-Dimer after withdrawal of OAT, D-Dimer-based treatment