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Rivaroxaban for the Prevention of Venous Thromboembolism in Asian Patients With Cancer

Primary Purpose

Rivaroxaban, Cancer-associated Thrombosis, Recurrence

Status
Completed
Phase
Phase 4
Locations
Korea, Republic of
Study Type
Interventional
Intervention
Rivaroxaban
Sponsored by
Seoul National University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rivaroxaban

Eligibility Criteria

20 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Patients ≥ 20 years old and active cancer and newly-diagnosed, symptomatic or incidental proximal lower extremity DVT, PE or both
  • will have a life expectancy > 3 months
  • will be treated with anticoagulation therapy for at least 3 months.

Exclusion Criteria:

  • (1) Isolated asymptomatic distal DVT
  • (2) Intra-abdominal venous thrombosis or vascular access-induced thrombosis
  • (3) Hemodynamically unstable PE, indicating systolic blood pressure <90 mmHg
  • (4)Eastern Cooperative Oncology Group (ECOG) performance status score of 3 or 4
  • (5) History of total gastrectomy
  • (6) Overt brain metastasis. Patients who have controlled brain metastasis without need of glucocorticoid are eligible
  • (7) History of recent major or clinically relevant bleeding within the previous 4 weeks
  • (8) Conditions associated with a high risk of serious bleeding (active peptic ulcer or recent neurosurgery)
  • (9) Other serious illness or medical conditions (illnesses requiring chronic anticoagulation therapy, unstable cardiac disease despite treatment, myocardial infarction within 3 months prior to study entry, significant neurologic or psychiatric diseases including dementia or seizure, active uncontrolled infection, other serious medical conditions)
  • (10)Inadequate renal function; creatinine clearance < 30 ml/min
  • (11) Inadequate hepatic function: alanine aminotransferase > 3 times the upper limit of normal (ULN) (if liver metastasis, alanine aminotransferase > 5 times the ULN or total bilirubin >2 times the ULN (if liver metastasis, total bilirubin >3 times the ULN)
  • (12) Baseline platelet count < 75,000 per cubic millimeter or Hb < 8g/dL
  • (13) Plan of treatment with bevacizumab or other anti-cancer drugs known to increase the bleeding risk
  • (14) Women of childbearing potential who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for the entire study period, who are using a prohibited contraceptive method, or who are pregnant or breastfeeding
  • (15) Patients requiring strong cytochrome P450 3A4 (CYP3A4) inducers (rifampin, phenobarbital) or strong CYP3A4 inhibitors (HIV protease inhibitor, systemic ketoconazole) treatments
  • (16) Patients with inferior vena cava filter placement or underwent catheter-directed thrombolysis or stent placement for the treatment of index VTE

Sites / Locations

  • Seoul National University Bundang Hospital

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

oral rivaroxaban in cancer-associated VTE

Arm Description

Outcomes

Primary Outcome Measures

recurrent symptomatic deep venous thrombosis, pulmonary embolism or both
Recurrent DVT will be defined if a new onset non-compressibility of a previously compressible venous segment on ultrasonography is identified or if there is a new constant intraluminal filling defect on venography. Unequivocal extension of the thrombus will be needed to diagnose the recurrence on the same extremity of the first event unless new concomitant PE or DVT in other extremities is confirmed. Recurrent PE will be diagnosed by high probability on ventilation/perfusion lung scan, or by the presence of non-enhancing filling defects in the pulmonary vasculature on pulmonary CT angiogram.

Secondary Outcome Measures

incidentally detected VTE
Incidentally detected recurrent thrombosis will be defined as objectively-proven thrombosis during the study period by imaging studies that are performed for reasons other than suspected VTE.
Major or clinically relevant non-major bleedings
Major bleeding will be defined if it is associated with death, occurs at critical sites (intracranial, intraspinal, intraocular, retroperitoneal, or pericardial area), and results in a need for a transfusion of at least 2 units of packed red cells, or lead to a drop in hemoglobin of more than 2 g/dL. Clinically relevant non-major bleeding will be defined as relevant bleeding that did not meet the criteria for major bleeding but is associated with medical intervention, unscheduled visit, interruption or discontinuation of a study drug, or discomfort or impairment of activities of daily life
recurrent VTE according to the risk of clinical prediction rule
Risk of recurrent VTE can be differentiated by risk prediction rule, named Ottawa score. Ottawa score is composed of gender, primary tumor site, stage, and prior VTE and ranged between -3 and 3 score points. Patients with a score <1 will be considered as having low risk for recurrence and patients with a score >1 considered as having high risk for recurrence.

Full Information

First Posted
November 5, 2013
Last Updated
January 6, 2017
Sponsor
Seoul National University Hospital
Collaborators
Korean Society of Hematology Thrombosis Working Party
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1. Study Identification

Unique Protocol Identification Number
NCT01989845
Brief Title
Rivaroxaban for the Prevention of Venous Thromboembolism in Asian Patients With Cancer
Official Title
Prospective, Multicenter Study Investigating Efficacy and Safety of Oral Rivaroxaban for the Prevention of Recurrent Venous Thromboembolism in Korean Patients With Cancers
Study Type
Interventional

2. Study Status

Record Verification Date
January 2017
Overall Recruitment Status
Completed
Study Start Date
October 2013 (undefined)
Primary Completion Date
December 2016 (Actual)
Study Completion Date
December 2016 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Seoul National University Hospital
Collaborators
Korean Society of Hematology Thrombosis Working Party

4. Oversight

Data Monitoring Committee
No

5. Study Description

Brief Summary
Rivaroxaban has been developed in the various clinical settings, prevention of venous thromboembolism (VTE)after major orthopedic surgery, prevention of stroke in atrial fibrillation, and in the treatment of acute coronary syndromes. And, in the EINSTEIN-pulmonary embolism (PE) and EINSTEIN-deep venous thrombosis (DVT) programs, rivaroxaban showed non-inferior to standard therapy for the treatment of PE and DVT. However, there has been limited experience of rivaroxaban with secondary VTE prophylaxis in cancer patients. Although cancer-associated DVT or PE was included in previously mentioned EINSTEIN programs, only approximately 5% of the total populations were cancer patients in these studies. Thus, investigators could not automatically translate the results of these studies into the real practice management of cancer-associated VTE patients. Moreover, until now, new oral anticoagulants, including dabigatran and rivaroxaban, have been compared to long-term warfarin therapy, which were well-known inferior agent, but not low molecular weight heparin. In this sense, investigators feel that new oral anticoagulants, particularly rivaroxaban, should be re-investigated in this highly specific patients group. Therefore, investigators are planning to conduct a prospective study evaluating the efficacy and safety of rivaroxaban in Korean patients with cancer-associated VTE.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rivaroxaban, Cancer-associated Thrombosis, Recurrence, Bleeding

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 4
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
127 (Actual)

8. Arms, Groups, and Interventions

Arm Title
oral rivaroxaban in cancer-associated VTE
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
Rivaroxaban
Other Intervention Name(s)
Xarelto
Intervention Description
Rivaroxaban 15mg twice daily for the first 3 weeks, followed by 20mg once daily during 6 months
Primary Outcome Measure Information:
Title
recurrent symptomatic deep venous thrombosis, pulmonary embolism or both
Description
Recurrent DVT will be defined if a new onset non-compressibility of a previously compressible venous segment on ultrasonography is identified or if there is a new constant intraluminal filling defect on venography. Unequivocal extension of the thrombus will be needed to diagnose the recurrence on the same extremity of the first event unless new concomitant PE or DVT in other extremities is confirmed. Recurrent PE will be diagnosed by high probability on ventilation/perfusion lung scan, or by the presence of non-enhancing filling defects in the pulmonary vasculature on pulmonary CT angiogram.
Time Frame
within the six months after the diagnosis of index VTE
Secondary Outcome Measure Information:
Title
incidentally detected VTE
Description
Incidentally detected recurrent thrombosis will be defined as objectively-proven thrombosis during the study period by imaging studies that are performed for reasons other than suspected VTE.
Time Frame
within six months after the diagnosis of VTE
Title
Major or clinically relevant non-major bleedings
Description
Major bleeding will be defined if it is associated with death, occurs at critical sites (intracranial, intraspinal, intraocular, retroperitoneal, or pericardial area), and results in a need for a transfusion of at least 2 units of packed red cells, or lead to a drop in hemoglobin of more than 2 g/dL. Clinically relevant non-major bleeding will be defined as relevant bleeding that did not meet the criteria for major bleeding but is associated with medical intervention, unscheduled visit, interruption or discontinuation of a study drug, or discomfort or impairment of activities of daily life
Time Frame
within six months after the diagnosis of VTE
Title
recurrent VTE according to the risk of clinical prediction rule
Description
Risk of recurrent VTE can be differentiated by risk prediction rule, named Ottawa score. Ottawa score is composed of gender, primary tumor site, stage, and prior VTE and ranged between -3 and 3 score points. Patients with a score <1 will be considered as having low risk for recurrence and patients with a score >1 considered as having high risk for recurrence.
Time Frame
within six months after the diagnosis of VTE

10. Eligibility

Sex
All
Minimum Age & Unit of Time
20 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Patients ≥ 20 years old and active cancer and newly-diagnosed, symptomatic or incidental proximal lower extremity DVT, PE or both will have a life expectancy > 3 months will be treated with anticoagulation therapy for at least 3 months. Exclusion Criteria: (1) Isolated asymptomatic distal DVT (2) Intra-abdominal venous thrombosis or vascular access-induced thrombosis (3) Hemodynamically unstable PE, indicating systolic blood pressure <90 mmHg (4)Eastern Cooperative Oncology Group (ECOG) performance status score of 3 or 4 (5) History of total gastrectomy (6) Overt brain metastasis. Patients who have controlled brain metastasis without need of glucocorticoid are eligible (7) History of recent major or clinically relevant bleeding within the previous 4 weeks (8) Conditions associated with a high risk of serious bleeding (active peptic ulcer or recent neurosurgery) (9) Other serious illness or medical conditions (illnesses requiring chronic anticoagulation therapy, unstable cardiac disease despite treatment, myocardial infarction within 3 months prior to study entry, significant neurologic or psychiatric diseases including dementia or seizure, active uncontrolled infection, other serious medical conditions) (10)Inadequate renal function; creatinine clearance < 30 ml/min (11) Inadequate hepatic function: alanine aminotransferase > 3 times the upper limit of normal (ULN) (if liver metastasis, alanine aminotransferase > 5 times the ULN or total bilirubin >2 times the ULN (if liver metastasis, total bilirubin >3 times the ULN) (12) Baseline platelet count < 75,000 per cubic millimeter or Hb < 8g/dL (13) Plan of treatment with bevacizumab or other anti-cancer drugs known to increase the bleeding risk (14) Women of childbearing potential who are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for the entire study period, who are using a prohibited contraceptive method, or who are pregnant or breastfeeding (15) Patients requiring strong cytochrome P450 3A4 (CYP3A4) inducers (rifampin, phenobarbital) or strong CYP3A4 inhibitors (HIV protease inhibitor, systemic ketoconazole) treatments (16) Patients with inferior vena cava filter placement or underwent catheter-directed thrombolysis or stent placement for the treatment of index VTE
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Soo-Mee Bang, MD, PhD
Organizational Affiliation
Seoul National University Bundang Hospital
Official's Role
Principal Investigator
Facility Information:
Facility Name
Seoul National University Bundang Hospital
City
Seongnam
ZIP/Postal Code
463-707
Country
Korea, Republic of

12. IPD Sharing Statement

Learn more about this trial

Rivaroxaban for the Prevention of Venous Thromboembolism in Asian Patients With Cancer

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