newly diagnosed proximal deep vein thrombosis (DVT) and/or pulmonary embolism (PE)
Conditions
Interventions
Subcutaneous injections with the anticoagulant as well as blood sampling 4
times during the study.
Cancer
Deep vein thrombosis
Pulmonary embolism
Sponsors
Fondazione FADOI Italian Federation of Hospital Internists
Eligibility
Age
18 Years to 64 Years
Inclusion criteria
Inclusion criteria: A newly diagnosed, objectively confirmed symptomatic or unsuspected, proximal lower limb DVTor a symptomatic PE or an unsuspected PE in a segmental or more proximal pulmonary artery. and any type of cancer (other than basal cell or squamous cell carcinoma of the skin, primary brain tumors or intracerebral metastasis and acute leukemia that meets at least one of the following: Active cancer defined as diagnosis of cancer within 6 months before the study inclusion, or receiving treatment for cancer at the time of inclusion or any treatment for cancer during 6 months prior to randomization, or recurrent locally advanced or metastatic cancer. Cancer diagnosed within 2 years before the study inclusion (history of cancer).
Exclusion criteria
Exclusion criteria: less than 18 years of age. ECOG performance status III or IV. Life expectancy of less than 6 months. Related to anti coagulant therapy: administration of therapeutic doses of LMWH, fondaparinux, or unfractionated heparin (UFH) for more than 72 hours before randomization. Three 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 anti coagulant treatment for a disease other than the index VTE. Concomitant use of strong inhibitors or inducers of both cytochrome P-450 3A4 and P-Glycoprotein. Related to bleeding risks: concomitant thienopyridine therapy (clopidogrel, pasugrel or ticagrelor) or aspirin over 165 mg daily oe dual antiplatlet therapy. Active bleeding or a high risk of bleeding contraindicating anticoagulant therapy. `recent (in the last 1 month prior to randomization) brain, spinal or ophthalmic surgery. Hemoglobin level lower than 8 g/dl (5.0 mmil/Liter or platelet count less than 75 x 10 to the 9th/L or history of heparin induced thrombocytopenia. Creatinine clearance less than 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 of of the higher of the upper limit of the normal range. uncontrolled hypertension (systolic BP more than 180 mm HG or diastolic BP more than 100 mm Hg despite antihypertensive treatment. Standard criteria: Bacterial endocarditis, hypersensitivity to the study drugs or to any of their excipients, patients participating in other pharmacy therapeutic program with an experimental therapy that is know to effect the coagulation system, women of child bearing potential (WOCBP) who do not practice a medically accepted high effective contraception during the trial and one months beyond, pregnancy or breast feeding, any condition that is judged by the investigator that would place the subject at increased risk or harm if (s)he participated in the study.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary efficacy outcome: Objectively confirmed recurrent VTE occurring during the study treatment 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) Primary safety outcome is major bleeding, defined (as per ISTH guidelines), as acute clinically overt bleeding associated with one or more of the following: - decrease in hemoglobin of 2 g/dl (1.2 mmol/L) or more; - transfusion of 2 or more units of packed red blood cells;. - bleeding that occurs in at least one critical site [intracranial,intra-spinal, intraocular (within the corpus of the eye; thus, a conjunctival bleed is not an intraocular bleed), pericardial, intraarticular, intramuscular with compartment syndrome, or retroperitoneal]; - bleeding that is fatal; - bleeding that necessitates acute surgical intervention | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary efficacy outcomes: The individual components of the primary efficacy outcome Symptomatic recurrence of the VTE All cause death The composite of primary efficacy outcome plus major bleeding The composite of primary efficacy outcome plus major bleeding plus all cause death The composite of primary efficacy outcome plus all cause death Any major cardiovascular event, fatal or non fatal (including acute Myocardial Infarction or ischemic stroke) All venous thromboembolic events (including splanchnic vein thrombosis and cerebral vein thrombosis) Quality of Life according to the Anti-Cot Treatment Scale (ACTS) (see appendix 2) Secondary safety outcomes include: · Clinically relevant non-major bleeding event defined as acute clinically overt bleeding that does not meet the criteria for major and consists of: - any bleeding compromising hemodynamics; - spontaneous hematoma larger than 25 cm2, or 100 cm2 if there was a traumatic cause; - intramuscular hematoma documented by ultrasonography; - epistaxis or gingival bleeding requiring tamponade or other medical intervention or bleeding from venipuncture for >5 minutes; - hematuria that was macroscopic and was spontaneous or lasted for more than 24 hours after invasive procedures; - hemoptysis, hematemesis or spontaneous rectal bleeding requiring endoscopy or other medical intervention; - or any other bleeding considered to have clinical consequences for a patient such as medical intervention, the need for unscheduled contact (visit or telephone call) with a physician, or temporary cessation of a study drug, or associated with pain or impairment of activities of daily life. · Clinically relevant bleeding defined as the composite of major and clinically relevant non-major bleeding · Permanent early discontinuation of study drug due to safety reasons. | — |
Countries
Belgium, France, Germany, Israel, Italy, Netherlands, Poland, Portugal, Spain, United Kingdom, United States of America
Outcome results
None listed