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

• ClinicalTrials.gov Identifier: NCT03895502
• Recruitment Status: Active, not recruiting
• First Posted: March 29, 2019
• Last Update Posted: August 18, 2022
• Sponsor: Takeshi Morimoto
• Information provided by (Responsible Party): Takeshi Morimoto, Kyoto University, Graduate School of Medicine

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Venous Thrombosis; Neoplasms; Anticoagulant	Drug: 12-month Edoxaban; Drug: 3-month Edoxaban	Phase 4

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 Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 605 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Optimal Duration of Anticoagulation Therapy for Isolated Distal Deep Vein Thrombosis in Patients With Cancer Study
• Actual Study Start Date: May 27, 2019
• Estimated Primary Completion Date: June 30, 2023
• Estimated Study Completion Date: August 31, 2023

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. Symptomatic VTE recurrence event or VTE related death event [ Time Frame: 12 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 :

1. Major bleeding event (ISTH criteria) [ Time Frame: 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.
2. All-cause death [ Time Frame: 12 months ]
3. Symptomatic VTE recurrence event [ Time Frame: 12 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.
4. VTE related death event [ Time Frame: 12 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.)
5. Clinically relevant non-major (CRNM) bleeding [ Time Frame: 12 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.
6. Clinically relevant bleeding [ Time Frame: 12 months ]
   Clinically relevant bleeding is defined as major or CRNM bleeding.
7. Bleeding related death event [ Time Frame: 12 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.
8. Unsuspected recurrent DVT by follow-up ultrasound examinations [ Time Frame: 12 months ]
   Unsuspected DVT by follow-up ultrasound examinations is a thrombus that is detected during follow-up ultrasound testing without suspicion of DVT.
9. Unsuspected recurrent VTE by any imaging examinations [ Time Frame: 12 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.
10. Change of serum D-dimer levels during follow-up period [ Time Frame: 12 months ]
11. Any adverse outcomes during invasive procedures [ Time Frame: 12 months ]
    Adverse outcomes include bleeding events, recurrent VTE events, all-cause deaths.

Eligibility Criteria

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

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.

Contacts and Locations

Locations

Japan

Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine

Kyoto, Japan, 606-8507

Sponsors and Collaborators

Takeshi Morimoto

Investigators

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

More Information

• Responsible Party: Takeshi Morimoto, Professor of Medicine, Kyoto University, Graduate School of Medicine
• ClinicalTrials.gov Identifier: NCT03895502
• Other Study ID Numbers: Y0019
• First Posted: March 29, 2019
• Last Update Posted: August 18, 2022
• Last Verified: August 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Takeshi Morimoto, Kyoto University, Graduate School of Medicine:

Venous Thrombosis; Neoplasms; Anticoagulant

Additional relevant MeSH terms:

Thrombosis; Venous Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases; Edoxaban; Factor Xa Inhibitors; Antithrombins; Serine Proteinase Inhibitors; Protease Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action; Anticoagulants