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

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.

Study Overview

• Status: Completed
• Conditions: Neoplasms; Venous Thrombosis; Anticoagulant
• Intervention / Treatment: Drug: 12-month Edoxaban; Drug: 3-month Edoxaban

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).

• Study Type: Interventional
• Enrollment (Actual): 605
• Phase: Phase 4

Contacts and Locations

Study Locations

• Japan
  • Kyoto, Japan, 606-8507
    • Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 12-month Edoxaban; Edoxaban for 12 months	Drug: 12-month Edoxaban; Prescription of Edoxaban for 12 months
Active Comparator: 3-month Edoxaban; Edoxaban for 3 months	Drug: 3-month Edoxaban; Prescription of Edoxaban for 3 months

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
All-cause death		12 months
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
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

Collaborators and Investigators

• Sponsor: Takeshi Morimoto
• Investigators: Study Chair: Takeshi Kimura, MD, PhD, Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine

Study record dates

Study Major Dates

• Study Start (Actual): May 27, 2019
• Primary Completion (Actual): June 30, 2023
• Study Completion (Actual): August 31, 2023

Study Registration Dates

• First Submitted: March 27, 2019
• First Submitted That Met QC Criteria: March 28, 2019
• First Posted (Actual): March 29, 2019

Study Record Updates

• Last Update Posted (Actual): October 4, 2023
• Last Update Submitted That Met QC Criteria: October 2, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: Neoplasms; Anticoagulant; Venous Thrombosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Embolism and Thrombosis; Thrombosis; Venous Thrombosis; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Protease Inhibitors; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Anticoagulants; Edoxaban
• Other Study ID Numbers: Y0019

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No