Optimal Duration of Anticoagulation Therapy for Low-risk Pulmonary Embolism Patients With Cancer (ONCO PE)

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.

Study Overview

• Status: Active, not recruiting
• Conditions: Neoplasms; Venous Thrombosis; Anticoagulants
• Intervention / Treatment: Drug: Long DOAC; Drug: Short DOAC

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).

• Study Type: Interventional
• Enrollment (Actual): 177
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Yugo Yamashita, MD, PhD; Phone Number: +81-75-751-4255; Email: yyamashi@kuhp.kyoto-u.ac.jp

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 to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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)

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
Active Comparator: Long DOAC; Administration of Rivaroxaban for 18 months	Drug: Long DOAC; Administration of Rivaroxaban for 18 months
Active Comparator: Short DOAC; Administration of Rivaroxaban for 6 months	Drug: Short DOAC; Administration of Rivaroxaban for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	18 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.	3 months
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).	3 months
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.	3 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.	3 months
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.	3 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.	18 months
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).	18 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.	18 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.	18 months
Clinically relevant bleeding	Clinically relevant bleeding is defined as major or CRNM bleeding.	18 months
All-cause death	Death from any cause.	18 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.	18 months
Any adverse outcomes during invasive procedures	Adverse outcomes include bleeding events, recurrent VTE events, all-cause deaths.	18 months

Collaborators and Investigators

• Sponsor: Takeshi Morimoto
• Collaborators: Bayer Yakuhin, Ltd.

Study record dates

Study Major Dates

• Study Start (Actual): February 18, 2021
• Primary Completion (Anticipated): September 30, 2024
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: January 22, 2021
• First Submitted That Met QC Criteria: January 22, 2021
• First Posted (Actual): January 26, 2021

Study Record Updates

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

More Information

Terms related to this study

• Keywords: Neoplasms; Anticoagulants; Venous Thrombosis
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Respiratory Tract Diseases; Lung Diseases; Embolism and Thrombosis; Embolism; Thrombosis; Venous Thrombosis; Pulmonary Embolism
• Other Study ID Numbers: Y0081

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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