Prevention of venous thromboembolism in patients who have been hospitalized for a medical illness MedDRA version: 9.1 Level: LLT Classification code 10012108 Term: Deep venous thrombosis prophylaxis
Conditions
Interventions
Trade Name: Xarelto
Product Name: Rivaroxaban
Product Code: BAY 59-7939
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Rivaroxaban
CAS Number: 366789-02-8
Current Sponsor code: BAY 59-79
Sponsors
Bayer HealthCare AG
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Subjects who meet the following criteria may be included in the study: 1. Male and female patients aged 40 years or more with no upper age limit 2. Patients at risk of venous thromboembolic events being hospitalized for acute medical conditions as follows: · Heart failure, NYHA class III or IV · Active cancer (eg, admitted for chemotherapy or for treatment of a complication of the active cancer) · Acute ischemic stroke · Acute infectious and inflammatory diseases, including acute rheumatic diseases · Acute respiratory insufficiency 3. At least one additional risk factor for VTE: a. Severe varicosis b. Chronic venous insufficiency c. History of cancer d. History of DVT or PE e. History of heart failure NYHA Class III or IV f. Thrombophilia (hereditary or acquired) g. Recent major surgery (6 to 12 weeks) h. Recent serious trauma (6 to 12 weeks) i. Hormone replacement therapy j. Advanced age = 75 years k. Morbid obesity (body mass index [BMI] = 35 kg/m2) l. Acute infectious disease contributing to hospitalization Patients with heart failure NYHA class III or IV who have had previous hospitalizations for heart failure NYHA class III or IV or are chronically in NYHA class III or IV status, patients with active cancer and patients with acute ischemic stroke with lower extremity paresis or paralysis are not required to have an additional risk factor. 4. Anticipated complete immobilization for at least one day during the hospitalization and anticipated decreased level of mobility for at least 4 days following randomization in any type of care setting (eg, hospital, intermediate care or rehabilitation centre, managed care in home, etc), and additional anticipated ongoing decreased mobility thereafter. Definition of complete immobilization, decreased mobility and ongoing decreased mobility are as follows: Complete Immobilization: The patient is totally confined by his or her illness to bed or chair. The patient may be allowed to use a bedside commode or with assistance may be allowed bathroom privileges. Decreased Level of Mobility: Immobilization caused by the illness requiring the patient to remain in bed or chair more than 50% of the time during daytime hours. Ongoing Decreased Mobility: Immobilization caused by the illness requiring the patient to remain in bed or chair during daytime hours more than was normal and usual for the patient prior to hospitalization. 5. Hospitalized less than 72 hours before randomization 6. Patients’ written informed consent for participation after receiving detailed written and oral information prior to any study specific procedures. Analphabetic or illiterate patients may be enrolled by verbal informed consent if allowed by local regulations and approved by the local Institutional Review Board (IRB) or Ethics Committee (EC). The patient’s decision to withdraw from the study at any time will be respected. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1. Conditions that contraindicate the use of antithrombotic therapy with the LMWH enoxaparin 2. Conditions that may increase the risk of bleeding, including intracranial hemorrhage, such as: • Clinically significant bleeding, within 30 days of randomization • Major surgery, biopsy of a parenchymal organ, ophthalmic surgery, or serious trauma within 6 weeks before randomization • A presenting diagnosis for which surgery is intended during hospitalization (eg, cholecystitis and planned cholecystectomy) • Have a known coagulopathy or bleeding diathesis (eg, disseminated intravascular coagulation, clinically relevant thrombocytopenia) or an international normalized ratio (INR) known to be > 1.5 at the time of screening unrelated to VKA therapy • History of hemorrhagic stroke at any time in the past, evidence of primary intracranial hemorrhage on CT or MRI scan of the brain, or clinical presentation consistent with intracranial hemorrhage (eg, severe headache or new neurologic deficit after fibrinolytic therapy) • Recent severe head trauma within 30 days of randomization which includes concussion, skull fracture, or hospitalization for head injury • Known intracranial neoplasm, cerebral metastases, arteriovenous malformation, or aneurysm 3. Required drugs or procedures, such as: • More than 2 days of prophylactic use of anticoagulants. Up to 2 doses of LMWH or up to 6 doses of unfractionated heparin pre-randomization are allowed. • Systemic treatment with more than 2 doses of strong inhibitors of cytochrome P450 3A4 (CYP 3A4), such as ketoconazole or protease inhibitors, within 4 days before randomization or planned treatment during the time period of the study drug administration • Indication for fibrinolysis or need for continued treatment with anticoagulant agents for more than 14 days • Treatment with or use of mechanical thromboprophylaxis (eg, pneumatic compression devices, foot pumps) for VTE prevention 4. Concomitant conditions or diseases, such as: • Known allergy to rivaroxaban or any of its excipients • Severe renal insufficiency (ie, calculated creatinine clearance 5 x ULN or ALT > 3 x ULN plus total bilirubin > 2 x ULN and the ratio of direct to total bilirubin = 50% (see Section 4.3) • Known human immunodeficiency virus (HIV) infection at screening • Sustained uncontrolled systolic blood pressure of = 180 mmHg or diastolic pressure of = 100 mmHg at time of screening despite treatment • History of ongoing drug or alcohol abuse • Cardiogenic or septic shock with the need for vasopressor(s), such as noradrenaline, and/or inotropes, such as dobutamine or milrinone • Any severe condition that would limit life expectancy to less than 6 months, ie, advanced malignancy, etc 5. General: • Unilateral or bilateral above knee lower extremity amputation • Inability to take oral medication or otherwise unable or unwilling to undergo/perform study-specified procedures • Have received an experimental drug or used an experimental medical device within 30 days before the planned start of treatment • Pregnancy or breast-feeding or any plan to become pregnant during the study. Women with child-bearing potential not using adequate birth control method. Note that as an adeq
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The objective of this study is to demonstrate (1) the superior efficacy of VTE prophylaxis with oral rivaroxaban 10 mg once daily administered for 35 +/- 4 days to SC enoxaparin 40 mg once daily (OD) administered for 10 +/- 4 days in men and women aged 40 years or above who have been hospitalized for a medical illness and (2) the non-inferiority of VTE prophylaxis with oral rivaroxaban 10 mg once daily administered for 10 +/- 4 days to SC enoxaparin 40 mg once daily for 10 +/- 4 days in the same patient population. The safety of rivaroxaban and enoxaparin will be compared as well.;Secondary Objective: ;Primary end point(s): There are two primary efficacy endpoints: Primary Efficacy Endpoint 1 (test of superiority – Day 35 ± 4 days) Primary Efficacy Endpoint 1 is defined as a composite endpoint of the following components: • Asymptomatic proximal lower extremity DVT detected by mandatory bilateral lower extremity venous ultrasonography up to Day 35 +/- 4 days • Symptomatic lower extremity DVT (proximal or distal) up to Day 35 + 4 days • Symptomatic non fatal PE up to Day 35 + 4 days • VTE related death up to Day 35 + 4 days Primary Efficacy Endpoint 2 (test of non-inferiority – Day 10 +/- 4 days) Primary Efficacy Endpoint 2 is defined as a composite endpoint of the following components: • Asymptomatic proximal lower extremity DVT detected by mandatory bilateral lower extremity venous ultrasonography up to Day 10 + 4 days Symptomatic lower extremity DVT (proximal or distal) up to Day 10 + 4 days • Symptomatic non fatal PE up to Day 10 + 4 days • VTE related death up to Day 10 + 4 days It should be noted that early VTE events (ie asymptomatic DVTs as well as symptomatic DVTs, PEs and VTE-related deaths) will be carried forward to Primary Efficacy Endpoint 1. The analysis of the primary efficacy endpoints will be solely based on the assessments made by the UAC and the CEAC. The major secondary endpoint is defined as the composite of the Primary Ef | — |
Countries
Austria, Bulgaria, Czech Republic, Denmark, Estonia, Finland, France, Germany, Greece, Hungary, Italy, Latvia, Lithuania, Netherlands, Poland, Portugal, Slovenia, Spain, Sweden, United Kingdom
Outcome results
None listed