Optimal Duration of Anticoagulation Therapy for Isolated Distal Deep Vein Thrombosis in Patients With Cancer Study

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the optimal duration of anticoagulation therapy (3 months versus 12 months) with direct oral anticoagulant (edoxaban) for isolated distal deep vein thrombosis.

Detailed Description
-----------------
Venous thromboembolism (VTE), including pulmonary embolism (PE) and deep vein thrombosis (DVT), is a major health problem in the world. There have been many clinical studies evaluating PE and/or proximal DVT, although data on isolated distal DVT (IDDVT) has been quite limited. However, IDDVT was reported to account for about half of all the diagnoses of DVT detected on ultrasound in daily clinical practice, and optimal management strategies for these patients are becoming clinically more relevant. The current American College of Chest Physicians (ACCP) guidelines suggest the same approach for IDDVT patients with cancer as proximal DVT patients with cancer. However, whether anticoagulation therapy should be continued indefinitely remains uncertain and the duration of treatment in these patients might vary widely in daily clinical practice. Recently, some observational studies reported that IDDVT patients with cancer have a high risk of VTE recurrence, suggesting the benefit of prolonged anticoagulation therapy. In this open-label, superiority trial, we will randomly assign IDDVT patients with active cancer to receive either edoxaban for 3 months (short DOAC group) or edoxaban for 12 months (long DOAC group).

Official Title
-----------------
Optimal Duration of Anticoagulation Therapy for Isolated Distal Deep Vein Thrombosis in Patients With Cancer Study

Conditions
-----------------
Venous Thrombosis, Neoplasms, Anticoagulant

Intervention / Treatment
-----------------
* Drug: 12-month Edoxaban
* Drug: 3-month Edoxaban


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients with newly found isolated distal deep vein thrombosis Patients complicated with active cancer Patients who are scheduled to be treated by anticoagulation therapy. Exclusion Criteria: Patients with anticoagulation therapy for the index event before 10 days of allocation. Patient under anticoagulation therapy for the purpose of other than the index event. Patients with thrombolysis therapy or IVC filter at the Index event. Patients with creatinine clearance less than 30 ml/min. Patients who are expected to have a life prognosis of 3 months or less. Patients with pulmonary embolism. Patients who are not appropriate for the participation of the study.

Ages Eligible for Study
-----------------
Minimum Age: 20 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 12-month Edoxaban<br>Edoxaban for 12 months | Drug: 12-month Edoxaban<br>* Prescription of Edoxaban for 12 months<br>|
| Active Comparator: 3-month Edoxaban<br>Edoxaban for 3 months | Drug: 3-month Edoxaban<br>* Prescription of Edoxaban for 3 months<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Symptomatic VTE recurrence event or VTE related death event | Symptomatic VTE recurrence event is defined as PE and/or DVT with symptoms accompanied by confirmation of new thrombus or exacerbation of the thrombus by objective imaging examinations or autopsy. VTE related death event is defined as death due to a documented PE (either an objective test prior to death of the subject or PE detected during autopsy) or unexplained death (i.e. death without a clear alternate cause and not a primary consequence of subject's underlying cancer.) | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Major bleeding event (ISTH criteria) | Major bleeding is defined as International Society of Thrombosis and Hemostasis (ISTH) major bleeding, which consisted of a reduction in the hemoglobin level by at least 2 g/dL, transfusion of at least 2 units of blood or symptomatic bleeding in a critical area or organ. | 12 months | 
| All-cause death |  | 12 months | 
| Symptomatic VTE recurrence event | Symptomatic VTE recurrence event is defined as PE and/or DVT with symptoms accompanied by confirmation of new thrombus or exacerbation of the thrombus by objective imaging examinations or autopsy. | 12 months | 
| VTE related death event | VTE related death event is defined as death due to a documented PE (either an objective test prior to death of the subject or PE detected during autopsy) or unexplained death (i.e. death without a clear alternate cause and not a primary consequence of subject's underlying cancer.) | 12 months | 
| Clinically relevant non-major (CRNM) bleeding | A bleeding event will be classified as a clinically relevant non-major bleeding event if it is overt (i.e. is symptomatic or visualized by examination) not meeting the criteria for major bleeding, requires medical attention or is associated with discomfort for the subject such as pain, or impairment of activities of daily life. | 12 months | 
| Clinically relevant bleeding | Clinically relevant bleeding is defined as major or CRNM bleeding. | 12 months | 
| Bleeding related death event | Bleeding related death event is defined as a bleeding event directly led to death. Examples of fatal bleeding events are an intracranial hemorrhage that led to herniation of the brain and death within 24 hours, and a massive gastrointestinal hemorrhage that results in shock, hemodynamic collapse, and death. | 12 months | 
| Unsuspected recurrent DVT by follow-up ultrasound examinations | Unsuspected DVT by follow-up ultrasound examinations is a thrombus that is detected during follow-up ultrasound testing without suspicion of DVT. | 12 months | 
| Unsuspected recurrent VTE by any imaging examinations | Unsuspected recurrent VTE is defined as thrombi that are detected during imaging testing performed for other reasons (e.g., computed tomography (CT) for cancer staging) and not for suspicion of DVT or PE. | 12 months | 
| Change of serum D-dimer levels during follow-up period |  | 12 months | 
| Any adverse outcomes during invasive procedures | Adverse outcomes include bleeding events, recurrent VTE events, all-cause deaths. | 12 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Venous Thrombosis, Neoplasms, Anticoagulant