Extrait

Background and study aims Antiphospholipid syndrome (APS), in patients with or without lupus, causes blood clots (thrombosis); any blood vessel in the body is at risk but most commonly a deep vein thrombosis (DVT) occurs. If a clot dislodges from the DVT, it can travel to the lungs, causing life-threatening pulmonary embolism (PE). Long-term anticoagulation with warfarin is the established treatment following DVT and/or PE to prevent further thrombosis, which can be life-threatening. Treatment with warfarin, although effective, is problematic as it can interact with numerous drugs and dietary constituents. Its action can also be affected by alcohol, smoking, other illnesses and exercise. Patients therefore require frequent INR blood tests (INR = International Normalised Ratio, the test used to monitor warfarin), which is inconvenient for the patient and costly for the NHS. In thrombotic APS patients, warfarin effects can be more erratic, because these patients have antiphospholipid antibodies which recognise proteins that bind to the surface of blood cells/vessels as "the enemy". They cause thrombosis and can also interfere with the effects of warfarin. Rivaroxaban is a recently introduced oral anticoagulant (blood thinner), which is given as fixed-dose tablets once daily. Unlike warfarin, rivaroxaban does not require routine monitoring because it has a predictable anticoagulant effect. Also, unlike warfarin, rivaroxaban does not interact with food or alcohol and has few drug interactions. It is unlikely that antiphospholipid antibodies will interfere with rivaroxaban's effects on blood clotting as, unlike warfarin, it has a very targeted effect on blood. We plan to compare the anticoagulant (blood thinning) effect of rivaroxaban with that of warfarin in patients with thrombotic APS, with or without lupus. We will do this by assessment of a specialised and excellent measure of anticoagulation called the 'thrombin generation test' (TGT). We will also assess rates of bleeding and further thrombosis, and compare serious adverse events and quality of life in patients on rivaroxaban with those on warfarin. If we can demonstrate that the anticoagulant effect of rivaroxaban is not inferior to that of warfarin, and that there is no increase in the rate of serious adverse effects (very unlikely - see below), we believe that this would provide good evidence to change practice for our patients, and make rivaroxaban the standard of care for patients with thrombotic APS, with or without lupus. Who can participate? Patients with thrombotic APS, with or without lupus, who have had a DVT and/or PE, and have been on warfarin at a target INR of 2.5 (range 2.0-3.0) for at least six months will be invited to take part in the study. What does the study involve? Patients will be randomly allocated to either remain on warfarin or to switch to rivaroxaban. Where possible, trial visits will be arranged to coincide with routine follow-up, and about three additional visits will be necessary. Trial visits will enable face-to-face contact with healthcare professionals to discuss any concerns and patients will be able to contact the Research Nurse to discuss any problems between visits. Two extra blood samples (each about four teaspoonfuls) will be taken prior to random allocation and six weeks later, in addition to routine blood tests. The trial treatment will last for six months and following this, patients will be offered appropriate anticoagulation. What are the possible benefits and risks of participating? Rivaroxaban is licensed in the UK and approved by NICE for the prevention of DVT/PE in patients undergoing hip and knee replacements and also for the treatment of DVT and prevention of recurrent DVT and PE following an acute DVT; and the prevention of stroke in patients with atrial fibrillation (an abnormal heart rhythm associated with an increased risk of stroke). Studies on tens of thousands of patients with DVT/PE or other conditions have shown that rivaroxaban is effective with a similar safety profile to warfarin. Indeed, to date in studies on a total of over 65,000 patients no major safety issues have emerged. It is likely that some patients with APS were included in the studies on DVT/PE, but there is no separate information available on this group. Where is the study run from? The study will take place at University College London Hospitals NHS Foundation Trust and Guys and St Thomas' NHS Foundation Trust (UK) When is the study starting and how long is it expected to run for? November 2012 to January 2015 Who is funding the project? Arthritis Research UK and Bayer PLC Who is the main contact? RAPS Trial Manager [email protected]

Critère d'inclusion

• Thrombotic antiphospholipid syndrome, with or without systemic lupus erythematosus

Liens

• ictrp
• isrctn