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

Bleeding Clinical Trial

Official title:

Prospective, Multicenter Study Investigating Efficacy and Safety of Oral Rivaroxaban for the Prevention of Recurrent Venous Thromboembolism in Korean Patients With Cancers

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01989845
• Other study ID #: KVTE13-01
• Status: Completed
• Phase: Phase 4
• First received: November 5, 2013
• Last updated: January 6, 2017
• Start date: October 2013
• Est. completion date: December 2016

Study information

• Verified date: January 2017
• Source: Seoul National University Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: Korea: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 127
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: All
• Age group: 20 Years and older

Eligibility

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

Study Design

Endpoint Classification: Bio-equivalence Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Bleeding
• Cancer-associated Thrombosis
• Recurrence
• Rivaroxaban
• Thromboembolism
• Thrombosis
• Venous Thromboembolism

Intervention

Drug:
• Rivaroxaban
Rivaroxaban 15mg twice daily for the first 3 weeks, followed by 20mg once daily during 6 months

Locations

Country	Name	City	State
Korea, Republic of	Seoul National University Bundang Hospital	Seongnam

Sponsors (2)

Lead Sponsor	Collaborator
Seoul National University Hospital	Korean Society of Hematology Thrombosis Working Party

Country where clinical trial is conducted

Korea, Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	within the six months after the diagnosis of index VTE	No
Secondary	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.	within six months after the diagnosis of VTE	No
Secondary	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	within six months after the diagnosis of VTE	Yes
Secondary	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.	within six months after the diagnosis of VTE	No