Patients with antiphospholipid syndrome (APS), with or without systemic lupus erythematosus (SLE). MedDRA version: 14.1 Level: PT Classification code 10002817 Term: Antiphospholipid syndrome System Organ Class: 10021428 - Immune system disorders
Conditions
Interventions
Trade Name: Xarelto
Product Name: Rivaroxaban
Pharmaceutical Form: Film-coated tablet
INN or Proposed INN: Rivaroxaban
CAS Number: 36678
Sponsors
University College London
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Patients with thrombotic APS, with or without SLE, who have had either a single episode of VTE whilst not on anticoagulation or recurrent episode(s) which occurred whilst off anticoagulation or on sub-therapeutic anticoagulant therapy 2) Patients with a target INR of 2.5 (range 2.0 – 3.0) 3) Treated with warfarin for a minimum period of six months since last VTE 4) Female patients must be using adequate contraception with exception to postmenopausal or sterilised women Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 148 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 8
Exclusion criteria
Exclusion criteria: 1) Previous arterial thrombotic events due to APS 2) Recurrent venous thromboembolic events whilst on warfarin 3) Pregnant or lactating women 4) Severe renal impairment (creatinine clearance (calculated using the Cockcroft & Gault Equation Appendix A) 2 x ULN) 6) Thrombocytopenia (platelets < 75 x 10^9/L) 7) Non-compliance on warfarin (based on clinical assessment) 8) Patients on azole antifungals (e.g. ketoconazole, itraconazole, voriconazole and posaconazole) 9) Patents on Human Immunodeficiency Virus (HIV) protease inhibitors (e.g. ritonavir) 10) Patients on strong CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine or phenobarbital) 11) Patients less than 18 years of age
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: The primary aim of the trial is to assess whether the anticoagulant effects of rivaroxaban are not inferior to those of warfarin. This will be achieved by comparing the percentage change in endogenous thrombin potential (ETP), assessed by the thrombin generation test (TGT), from randomisation to day 42. The TGT is a global measure of anticoagulation, which can assess the anticoagulant effects of both rivaroxaban and warfarin (drugs with very different modes of action on the coagulation mechanism). The TGTs will be performed in the UCL Haemostasis Research Unit.;Secondary Objective: 1) To compare the effectiveness of the treatment between the two arms of the trial: i) Further blood clots in blood vessels (venous thromboembolism) ii) A combination of further venous thromboembolism and other thrombotic events 2) To compare serious adverse events and all bleeding events in patients on rivaroxaban versus those on warfarin 3) To compare the completed quality of life questionnaires at baseline and at day 180 for patients on rivaroxaban versus those on warfarin. 4) To assess compliance to the study drugs by performing assays in the plasma from the patients on rivaroxaban (anti-Xa assay) and in patients on warfarin (INR and factor X amidolytic assay as an antiphospholipid antibody-independent assessment of anticoagulation). Percentage time in therapeutic range (TTR) between baseline and day 180 will be calculated in patients on warfarin.;Primary end point(s): Percentage change in endogenous thrombin potential (ETP), assessed by the thrombin generation test (TGT), from randomisation to day 42.;Timepoint(s) of evaluation of this end point: The time point for the primary outcome is at the first trial visit, which will take place 42 days (±12days) after trial randomisation. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): a) Efficacy: i) recurrent venous thromboembolism (VTE) alone; ii) a composite of recurrent VTE and other thrombotic events. iii) The thrombin generation curve will also be quantified in terms of: the lag-time; the time to peak; and peak thrombin concentration. b) Safety: i) serious adverse events; ii) all bleeding events. c) Quality of life (QoL): EQ5D 5L. d) Laboratory assessment of compliance: i) anti-Xa assay in patients on rivaroxaban; ii) factor X amidolytic assay as an antiphospholipid antibody-independent assessment of anticoagulation, in addition to an International Normalised Ratio (INR) in patients on warfarin, iii) percentage time in therapeutic range (TTR) between baseline and day 180 in patients on warfarin.;Timepoint(s) of evaluation of this end point: All bleeding and thrombotic events are going to be collected at each visit (day 42 (±12 days), day 90 (±21 days), day 180 (±21 days) and day 210 (±21 days)). Quality of life will be measured at baseline and at six months using the EQ 5D 5L questionnaire. Laboratory measures of compliance will be measured at day 42 (±12 days) on trial treatment. | — |
Countries
United Kingdom
Contacts
Public ContactSimon Clawson
University College London
Outcome results
None listed