Optimal Duration of Anticoagulation Therapy for Low-risk Pulmonary Embolism Patients With Cancer (ONCO PE)
Primary Purpose
Venous Thrombosis, Neoplasms, Anticoagulants
Status
Active
Phase
Phase 4
Locations
Japan
Study Type
Interventional
Intervention
Long DOAC
Short DOAC
Sponsored by
About this trial
This is an interventional treatment trial for Venous Thrombosis focused on measuring Venous Thrombosis, Neoplasms, Anticoagulants
Eligibility Criteria
Inclusion Criteria:
- Patients with active cancer (solid and hematologic malignancies) presenting with objectively newly confirmed pulmonary embolism who are scheduled to be treated by anticoagulation therapy.
- Patients with an simplified Pulmonary Embolism Severity Index (PESI) score of 1 or less
Exclusion Criteria:
- Contraindicated patients for rivaroxaban (Clinically significant liver disease, Bacterial endocarditis, Active bleeding, Inadequate contraceptive measures if of childbearing potential, Concomitant use of strong cytochrome P-450 3A4 inhibitors or inducers or P-glycoprotein inhibitors or inducers)
- Expected life expectancy <6 months
- Patients who do not provide written informed consent
- Patients who judged to be inappropriate for enrolment by the physician (including patients at a high risk of gastrointestinal or genitourinary bleeding)
Sites / Locations
- Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine
Arms of the Study
Arm 1
Arm 2
Arm Type
Active Comparator
Active Comparator
Arm Label
Long DOAC
Short DOAC
Arm Description
Administration of Rivaroxaban for 18 months
Administration of Rivaroxaban for 6 months
Outcomes
Primary Outcome Measures
VTE recurrence event Venous thromboembolism (VTE) recurrence event
VTE recurrence event is defined as pulmonary embolism (PE) and/or deep vein thrombosis (DVT) by confirmation of new thrombus or exacerbation of the thrombus by objective imaging examinations or autopsy.
Secondary Outcome Measures
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.
PE-related death event
PE-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).
A composite of PE-related death, symptomatic recurrent VTE, and major bleeding (ISTH criteria)
PE-related death event is defined as death due to a documented PE or unexplained death. 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. 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.
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.
Hospitalization for VTE recurrence or clinically relevant bleeding events
Hospitalization for VTE recurrence or bleeding events. VTE recurrence event is defined as PE and/or DVT by confirmation of new thrombus or exacerbation of the thrombus by objective imaging examinations or autopsy. Bleeding events are clinically relevant bleeding events, which is defined as major or clinically relevant non-major bleeding. 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 bleeding event is defined as overt bleeding (i.e. is symptomatic or visualized by examination) which is 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.
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.
PE-related death event
PE-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).
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.
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.
Clinically relevant bleeding
Clinically relevant bleeding is defined as major or CRNM bleeding.
All-cause death
Death from any cause.
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.
Any adverse outcomes during invasive procedures
Adverse outcomes include bleeding events, recurrent VTE events, all-cause deaths.
Full Information
NCT ID
NCT04724460
First Posted
January 22, 2021
Last Updated
April 2, 2023
Sponsor
Takeshi Morimoto
Collaborators
Bayer Yakuhin, Ltd.
1. Study Identification
Unique Protocol Identification Number
NCT04724460
Brief Title
Optimal Duration of Anticoagulation Therapy for Low-risk Pulmonary Embolism Patients With Cancer
Acronym
ONCO PE
Official Title
Optimal Duration of Anticoagulation Therapy for Low-risk Pulmonary Embolism Patients With Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
April 2023
Overall Recruitment Status
Active, not recruiting
Study Start Date
February 18, 2021 (Actual)
Primary Completion Date
September 30, 2024 (Anticipated)
Study Completion Date
December 31, 2024 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
Takeshi Morimoto
Collaborators
Bayer Yakuhin, Ltd.
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
The primary purpose of this study is to determine the optimal duration of anticoagulation therapy (6 months versus 18 months) with direct oral anticoagulant (DOAC) for cancer-associated low-risk pulmonary embolism patients. The major secondary purpose of this study is to investigate whether home treatment of cancer-associated low-risk pulmonary embolism patients with rivaroxaban is feasible, effective, and safe through an observational management study.
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 VTE, although data on low-risk PE, including incidental PE and asymptomatic PE has been quite limited. However, low-risk PE was reported to account for a large proportion of all the diagnoses of PE detected on computed tomography 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 weakly suggest the same approach for low-risk PE patients with cancer as other PE 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 low-risk patients with cancer have a high risk of VTE recurrence, suggesting the benefit of prolonged anticoagulation therapy. In this open-label, superiority trial, the investigators randomly assign low-risk PE patients with active cancer to receive either rivaroxaban for 6 months (short DOAC group) or rivaroxaban for 18 months (long DOAC group).
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Venous Thrombosis, Neoplasms, Anticoagulants
Keywords
Venous Thrombosis, Neoplasms, Anticoagulants
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
177 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Long DOAC
Arm Type
Active Comparator
Arm Description
Administration of Rivaroxaban for 18 months
Arm Title
Short DOAC
Arm Type
Active Comparator
Arm Description
Administration of Rivaroxaban for 6 months
Intervention Type
Drug
Intervention Name(s)
Long DOAC
Intervention Description
Administration of Rivaroxaban for 18 months
Intervention Type
Drug
Intervention Name(s)
Short DOAC
Intervention Description
Administration of Rivaroxaban for 6 months
Primary Outcome Measure Information:
Title
VTE recurrence event Venous thromboembolism (VTE) recurrence event
Description
VTE recurrence event is defined as pulmonary embolism (PE) and/or deep vein thrombosis (DVT) by confirmation of new thrombus or exacerbation of the thrombus by objective imaging examinations or autopsy.
Time Frame
18 months
Secondary Outcome Measure Information:
Title
Major bleeding event (ISTH criteria)
Description
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.
Time Frame
3 months
Title
PE-related death event
Description
PE-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).
Time Frame
3 months
Title
A composite of PE-related death, symptomatic recurrent VTE, and major bleeding (ISTH criteria)
Description
PE-related death event is defined as death due to a documented PE or unexplained death. 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. 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.
Time Frame
3 months
Title
Symptomatic VTE recurrence event
Description
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.
Time Frame
3 months
Title
Hospitalization for VTE recurrence or clinically relevant bleeding events
Description
Hospitalization for VTE recurrence or bleeding events. VTE recurrence event is defined as PE and/or DVT by confirmation of new thrombus or exacerbation of the thrombus by objective imaging examinations or autopsy. Bleeding events are clinically relevant bleeding events, which is defined as major or clinically relevant non-major bleeding. 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 bleeding event is defined as overt bleeding (i.e. is symptomatic or visualized by examination) which is 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.
Time Frame
3 months
Title
Major bleeding event (ISTH criteria)
Description
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.
Time Frame
18 months
Title
PE-related death event
Description
PE-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).
Time Frame
18 months
Title
Symptomatic VTE recurrence event
Description
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.
Time Frame
18 months
Title
Clinically relevant non-major (CRNM) bleeding
Description
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.
Time Frame
18 months
Title
Clinically relevant bleeding
Description
Clinically relevant bleeding is defined as major or CRNM bleeding.
Time Frame
18 months
Title
All-cause death
Description
Death from any cause.
Time Frame
18 months
Title
Bleeding-related death event
Description
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.
Time Frame
18 months
Title
Any adverse outcomes during invasive procedures
Description
Adverse outcomes include bleeding events, recurrent VTE events, all-cause deaths.
Time Frame
18 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
20 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Patients with active cancer (solid and hematologic malignancies) presenting with objectively newly confirmed pulmonary embolism who are scheduled to be treated by anticoagulation therapy.
Patients with an simplified Pulmonary Embolism Severity Index (PESI) score of 1 or less
Exclusion Criteria:
Contraindicated patients for rivaroxaban (Clinically significant liver disease, Bacterial endocarditis, Active bleeding, Inadequate contraceptive measures if of childbearing potential, Concomitant use of strong cytochrome P-450 3A4 inhibitors or inducers or P-glycoprotein inhibitors or inducers)
Expected life expectancy <6 months
Patients who do not provide written informed consent
Patients who judged to be inappropriate for enrolment by the physician (including patients at a high risk of gastrointestinal or genitourinary bleeding)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Takeshi Kimura, MD, PhD
Organizational Affiliation
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine
City
Kyoto
ZIP/Postal Code
606-8507
Country
Japan
12. IPD Sharing Statement
Plan to Share IPD
No
Learn more about this trial
Optimal Duration of Anticoagulation Therapy for Low-risk Pulmonary Embolism Patients With Cancer
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