Evaluation of the Use of Apixaban in Prevnetion of Thromboembolic Disease in Patients With Myeloma Trated With iMiDs

Study Overview
=================
Brief Summary
-----------------
To evaluate: the incidence of venous thromboembolic event (VTE) the incidence of hemorrhagic complications, In a population of patients with myeloma who are treated with IMiDs and require thromboprophylaxis for 6 months, using an oral anti-Xa anticoagulant, Apixaban, in a preventive scheme, 2.5 mg x2/day

Detailed Description
-----------------
MYELAXAT trial is multicentre, open trial which aims to evaluate the incidence of venous thromboembolic event (VTE) and the incidence of hemorrhagic complications. All patients with Myeloma treated with iMiDs and require thromboprophylaxis for 6 months, using an oral anti-Xa anticoagulant, Apixaban, in a preventive scheme, 2.5 mg x2/day

Official Title
-----------------
Evaluation of the Use of an Oral Direct Anti-Xa Anticoagulant, Apixaban, in Prevention of Venous Thromboembolic Disease in Patients Treated With IMiDs During Myeloma : a Pilot Study

Conditions
-----------------
Myeloma, Venous Thromboembolism

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


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Patients (men/women) aged more than 18 years All consecutive patients, with myeloma, in first-line treatment or in relapse, who are treated - With IMiDs (MPT, Melphalan -Prednisone -Thalidomide ; Lenalidomide - Dexamethasone). AND - who require prevention of venous thromboembolic events with Aspirin or Low molecular Weight Heparin (LMWH) for a minimum duration of 6 months At least, 2/3 of patients will be treated with Lenalidomide-Dexamethasone. Written informed consent Patients affiliated to the French social security system or equivalent Exclusion Criteria: Patient who needs curative anticoagulant treatment (heparin, LMWH, vitamin K antagonists, Dabigatran, Rivaroxaban, Apixaban) for an associated disorder (mechanical valve, atrial fibrillation or venous thromboembolic disease in the previous 6 months). Patient who needs preventive treatment with an anticoagulant in a post-operative context Patient who needs anti-platelet treatment (Aspirin, Clopidogrel, Prasugrel, Ticagrelor or dual anti-platelet therapy ) Patient with active bleeding or at a high risk of bleeding (ulcer disease, intracranial bleeding in the previous 6 months, uncontrolled hypertension) Patient having undergone a surgical intervention within the past 30 days likely to expose them to an haemorrhagic risk Active hepatic disease (hepatitis, cirrhosis) Severe renal insufficiency (creatinine clearance using the Cockcroft equation < 30 ml/mn) Known allergic reaction to Apixaban Contraindication to the use of an anticoagulant treatment Prohibited concomitant treatment inhibitors of CYP3A4 and P-gp : azole antimycotic agents (ketoconazole, itraconazole, voriconazole, posaconazole), inhibitors of HIV protease (ritonavir, indinavir, nelfinavir, atazanavir, saquinavir), specific macrolide antibiotics (clarithromycine, telithromycine) other antithrombotic treatment : salicylate derivates (aspirin, products containing aspirin), antiplatelet therapy, heparin (unfractionated heparin, low molecular weight heparin, danaparoide sodique, fondaparinux), hirudines, oral anticoagulants (vitamin K antagonists, rivaroxaban, dabigatran) Patient with AST or ALT rate > 3 times upper limit of normal Patient with Bilirubin rate > 1.5 times upper limit of normal Patient with Platelets rate < 75 G/l Patient with Creatinine Clearance (Cockcroft) < 30 ml/mn Incidental finding of a proximal Deep Venous Thrombosis on the screening ultrasound Patients refusing or unable to give a written consent of information Patient unable to comply with the protocol requirement, in the investigator's opinion Life expectancy less than 6 months Incarcerated patients Pregnancy or possibility of pregnancy within 6 months Females of childbearing potential without reliable contraception Ecog > 2

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
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Apixaban<br>oral direct anti-Xa anticoagulant | Drug: Apixaban<br>* 2.5mg x 2 per day during 6 months<br>* Other names: oral direct anti-Xa anticoagulant;|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Total VTE and VTE-related death. Major and clinically relevant non major bleeding - Major and clinically relevant non major bleeding, defined according to International Society of Thrombosis and haemostasis | Total VTE (fatal or non fatal pulmonary embolism, symptomatic distal or proximal DVT of lower limbs, and asymptomatic proximal DVT detected by bilateral compression ultrasound) and VTE-related death. - Major and clinically relevant non major bleeding, defined according to International Society of Thrombosis and haemostasis | 7 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| incidence of venous thromboembolic complications | incidence of venous thromboembolic complications, symptomatic and asymptomatic, according to the thrombotic risk stratification of patients (low or high risk) | 7 months | 
| incidence of venous thromboembolic complications | incidence of venous thromboembolic complications, symptomatic and asymptomatic, according to the time of treatment with iMiDs (diagnosis or relapse) | 7 months | 
| incidence of major and clinically relevant non major bleeding | incidence of major and clinically relevant non major bleeding according to the thrombotic risk strtification of patients (low or high risk) | 7 months | 
| incidence of arterial cardiovascular events | incidence of arterial cardiovascular events (myocardial infarction, ischemic stroke, TIA) | 7 months | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
venous thromboembolic disease, iMiDs, myeloma, antiXa anticoagulant