Apixaban for the treatment of venous thromboembolism in patients with cancer: a prospective randomized open blinded end-point (PROBE) study

Inclusion Criteria:

• Consecutive patients with a newly diagnosed, objectively confirmed: symptomatic or unsuspected, proximal lower-limb DVT or symptomatic PE or unsuspected PE in a segmental or more proximal pulmonary artery;
• Any type of cancer (other than basal-cell or squamous-cell carcinoma of the skin, primary brain tumor or intracerebral metastasis and acute leukemia);
• Signed and dated informed consent of the patient, available before the start of any specific trial procedure.

Exclusion Criteria:

• age <18 years;
• ECOG Performance Status III or IV;
• life expectancy of less than 6 months;

Related to anticoagulant treatment:

• administration of therapeutic doses of LMWH, fondaparinux, or unfractionated heparin (UFH) for more than 72 hours before randomization;
• 3 or more doses of a vitamin K antagonist before randomization;
• thrombectomy, vena cava filter insertion, or thrombolysis used to manage the index episode;
• indication for anticoagulant treatment for a disease other than the index VTE episode;

Related to bleeding risk:

• thienopyridine therapy (clopidogrel, prasugrel, or ticagrelor) or aspirin over 165 mg daily or dual antiplatelet therapy;
• active bleeding or a high risk of bleeding contraindicating anticoagulant treatment;
• recent (in the last 1 month prior to randomization) brain, spinal or ophthalmic surgery
• hemoglobin level lower than 8 g/dL (5.0 mmol/L) or platelet count <75x10^9/L or history of heparin induced thrombocytopenia;
• creatinine clearance < 30 ml /min based on the Cockcroft Gault equation;
• acute hepatitis, chronic active hepatitis, liver cirrhosis; or an alanine aminotransferase level 3 times or more and/or bilirubin level 2 times or more higher the upper limit of the normal range;
• uncontrolled hypertension (systolic BP> 180 mmHg or diastolic BP > 100 mmHg despite antihypertensive treatment);
• concomitant use of strong inhibitors or inducers of both cytochrome P-450 3A4 and P-Glycoprotein;

Standard criteria:

• bacterial endocarditis;
• hypersensitivity to the active substance or to any of the excipients of study drug;
• patients participation in other pharmaco therapeutic program with an experimental therapy that is known to effect the coagulation system;
• childbearing potential without proper contraceptive measures, pregnancy, or breast feeding;
• any condition that as judged by the Investigator would place the subject at increased risk of harm if he/she participated in the study.