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 thrombcembolic events being hospitalized for acute medical conditions as follows:
- Heart failure, NYHA Class III or IV
- Active cancer (e.g., 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:
- Severe varicosis
- Chronic venous insufficiency
- History of cancer
- History of CVT or PE
- History of heart failure NYHA Class III or IV
- Thrombophilia (hereditary or acquired)
- Recent major surgery (6 to 12 weeks)
- Recent serious trauma (6 to 12 weeks)
- Hormone replacement therapy
- Advanced age ≥ 75 years
- Morbid obesity (body mass index [BMI] ≥ 35 kg/m2)
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 extremely paresis or paralysis are not required to have an additional risk factor.
4. Anticipated complete immobilization during the first day of hospitalization and anticipated decreased level of mobility, anticipated hospital stay duration of at least 4 days following randomization and additional anticipated ongoing decreased mobility.
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 waking hours.
Ongoing Decreased Mobility: Immobilization caused by the illness requiring the patient to remain in bed or chair during waking 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.
Exclusion Criteria
Potential subjects who meet any of the following criteria will be excluded from the study:
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 (e.g., cholecystitis and planned cholecystectomy)
- Have a known coagulopathy or bleeding diathesis (e.g., 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 (e.g., 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. Ups 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 antithrombotic agents
- Treatment with or use of mechanical thromboprophylaxis (e.g., pneumatic compression devices, foot pumps) for VTE prevention
4. Concimatant conditions or diseases, such as:
- Known allergy to rivaroxaban or any of its excipients
- Severe renal dysfunction (i.e., calculated creatinine clearance <30 mL/min)
- Known significant liver disease (e.g., acute clinical hepatitis, chronic active hepatitis, cirrhosis) or LFT abnormalities (confirmed with repeat testing) which would require study medication discontinuation, i.e., ALT > 5 x ULN or ALT > 3 x ULN plus total bilirubin > 2 x ULN and the ration of direct to total bilirubin is ≥ 50%
- 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, e.g. 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 adequate method of birth control, any effective method including abstinence , barrier contraception and other recognized effective methods are acceptable. Oral contraception agents should be carefully assessed to determine if the risk of their use in patients at increased risk of venous thromboembolic complications is warranted.
- Previous participation in this study or any other study of rivaroxaban
- Employees of the investigator or study center, with direct involvement in the proposed study or other studies under the direction of that investigator or study center, as well as family members of the employees or the investigator
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