Apixaban for the Treatment of Venous Thromboembolism in Patients With Cancer

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

Official Title
-----------------
Apixaban for the Treatment of Venous Thromboembolism in Patients With Cancer: A Prospective Randomized Open Blinded End-Point (Probe) Study

Conditions
-----------------
Venous Thromboembolism

Intervention / Treatment
-----------------
* Drug: Apixaban
* Drug: Dalteparin


Participation Criteria
=================
Eligibility Criteria
-----------------
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.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apixaban<br>orally administered, at the dose of 10 mg bid for 7 days, followed by 5 mg bid (total period of treatment: six months) | Drug: Apixaban<br>* Tablets<br>|
| Active Comparator: Dalteparin<br>subcutaneously administered, at a dose of 200 IU/kg SC o.i.d for 1 month. Thereafter, dalteparin will be administered at a dose of 150 IU/kg o.i.d. for 5 months | Drug: Dalteparin<br>* Injections<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Recurrent venous thromboembolism | Primary efficacy outcome: objectively confirmed recurrent VTE occurring during the study period, that means the composite of: · proximal DVT of the lower limbs (symptomatic or unsuspected), DVT of the upper limb (symptomatic), PE (symptomatic or unsuspected) | 6 months |