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

Phase 4
Completed
Conditions
Neoplasms
Venous Thrombosis
Anticoagulant
Interventions
Drug: 12-month Edoxaban
Drug: 3-month Edoxaban
Registration Number
NCT03895502
Lead Sponsor
Takeshi Morimoto
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).

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
605
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.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
12-month Edoxaban12-month EdoxabanEdoxaban for 12 months
3-month Edoxaban3-month EdoxabanEdoxaban for 3 months
Primary Outcome Measures
NameTimeMethod
Symptomatic VTE recurrence event or VTE related death event12 months

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.)

Secondary Outcome Measures
NameTimeMethod
All-cause death12 months
Symptomatic VTE recurrence event12 months

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.

Clinically relevant bleeding12 months

Clinically relevant bleeding is defined as major or CRNM bleeding.

Unsuspected recurrent VTE by any imaging examinations12 months

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.

VTE related death event12 months

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.)

Major bleeding event (ISTH criteria)12 months

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.

Clinically relevant non-major (CRNM) bleeding12 months

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.

Bleeding related death event12 months

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.

Unsuspected recurrent DVT by follow-up ultrasound examinations12 months

Unsuspected DVT by follow-up ultrasound examinations is a thrombus that is detected during follow-up ultrasound testing without suspicion of DVT.

Change of serum D-dimer levels during follow-up period12 months
Any adverse outcomes during invasive procedures12 months

Adverse outcomes include bleeding events, recurrent VTE events, all-cause deaths.

Trial Locations

Locations (1)

Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine

🇯🇵

Kyoto, Japan

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