Rivaroxaban in Antiphospholipid Syndrome (RAPS)

• Register: ISRCTN
• Last refreshed on: 17 October 2016
• Main ID: ISRCTN68222801
• Date of registration: 18/10/2012
• Prospective Registration: Yes
• Primary sponsor: University College London (UK)
• Public title: Rivaroxaban in Antiphospholipid Syndrome (RAPS)
• Scientific title: A prospective randomised controlled phase II/III clinical trial of rivaroxaban versus warfarin in patients with thrombotic antiphospholipid syndrome, with or without systemic lupus erythematosus
• Date of first enrolment: 30/11/2012
• Target sample size: 156
• Recruitment status: Completed
• URL: http://isrctn.com/ISRCTN68222801
• Study type: Interventional
• Study design: Randomised interventional trial (Treatment)
• Phase: Phase II/III

Countries of recruitment

United Kingdom

Contacts

• Name: Simon Clawson

Key inclusion & exclusion criteria

Inclusion criteria: Current inclusion criteria as of 02/10/2013:
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 three months since last VTE
4. Female patients must be using adequate contraception with the exception of postmenopausal or sterilised women

Previous 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
Exclusion criteria: Current exclusion criteria as of 02/10/2013:
1. Previous arterial thrombotic events due to APS
2. Recurrent venous thromboembolic events whilst on warfarin at a therapeutic INR of 2.0-3.0
3. Pregnant or lactating women
4. Severe renal impairment (creatinine clearance [calculated using the Cockcroft & Gault formula Appendix A] < 30 mL/min (i.e. 29 mL/min or less)
5. Liver function tests ALT > 2 x ULN
6. Cirrhotic patients with Child Pugh B or C
7. Thrombocytopenia (platelets < 75 x 10^9/L)
8. Non-compliance on warfarin (based on clinical assessment)
9. Patients on azole antifungals (e.g. ketoconazole, itraconazole, voriconazole and posaconazole)
10. Patients on Human Immunodeficiency Virus (HIV) protease inhibitors (e.g. ritonavir)
11. Patients on strong CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine, phenobarbital or St John's Wort)
12. Patients less than 18 years of age
13. Refusal to consent to the site informing GP and healthcare professional responsible for anticoagulation care, of participation

Previous exclusion criteria:
1. Previous arterial thrombotic events due to APS
2. Recurrent venous thromboembolic events whilst on warfarin at a therapeutic INR of 2.0-3.0
3. Pregnant or lactating women
4. Severe renal impairment (creatinine clearance [calculated using the Cockcroft & Gault formula Appendix A of the protocol] < 30 mL/min (i.e. 29 mL/min or less)
5. Liver function tests ALT > 2 x ULN
6. Cirrhotic patients with Child Pugh B or C
7. Thrombocytopenia (platelets < 75 x 10^9/L)
8. Non-compliance on warfarin (based on clinical assessment)
9. Patients on azole antifungals (e.g. ketoconazole, itraconazole, voriconazole and posaconazole)
10. Patents on Human Immunodeficiency Virus (HIV) protease inhibitors (e.g. ritonavir)
11. Patients on strong CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine or phenobarbital)
12. Patients less than 18 years of age
13. Refusal to consent to CTU informing GP of participation

Age minimum:
Age maximum:
Gender: Both

Health Condition(s) or Problem(s) studied

Thrombotic antiphospholipid syndrome, with or without systemic lupus erythematosus
Musculoskeletal Diseases

Intervention(s)

1. 20 mg rivaroxaban taken orally once daily for patient without renal impairment (creatinine clearance = 50 mL/min), for six months.
2. 15 mg rivaroxaban taken orally once daily for patients with moderate renal impairment (creatinine clearance of 30 - 49 mL/min), for six months.
3. Warfarin: This is the control arm where the treatment of patients with warfarin will remain unchanged. Warfarin will be prescribed and dispensed in accordance with national guidance and warfarin anticoagulant monitoring will be undertaken by the patient's usual anticoagulation clinic, which may be based at one of the trial sites or locally to the patient, either within a hospital or primary care anticoagulation clinic setting, or by patient self-monitoring under medical supervision.

Primary Outcome(s)

The percentage change in ETP from randomisation to day 42

Secondary Outcome(s)

1. Efficacy
2. Safety
3. Quality of life (QoL)
4. Laboratory assessment of compliance

Secondary ID(s)

2012-002345-38

13117

Source(s) of Monetary Support

Arthritis Research UK (formerly ARC Arthritis Research Campaign) (UK), Bayer PLC (UK)