Rituximab Vasculitis Maintenance Study (RITAZAREM)
Rituximab is now established as an effective drug for anti-neutrophil cytoplasmic antibody (ANCA) vasculitis following major European and US trials reported in 2010. After a time, its effect wears off and the disease can return. This occurs in at least half of patients within 2 years of receiving Rituximab. A preliminary study in Cambridge has suggested that repeating rituximab every six months stops the disease returning and is safe.
The RITAZAREM trial will find out whether repeating rituximab stops vasculitis returning and whether it works better than the older treatments, azathioprine or methotrexate. It will also tell us how long patients remain well after the repeated rituximab treatments are stopped, and if repeated rituximab is safe. We should also learn useful information about the effects of rituximab on quality of life and economic measures. The trial results will help decide the best treatment for future patients who have their vasculitis initially treated with rituximab.
RITAZAREM aims to recruit patients with established ANCA vasculitis whose disease has come back 'relapsing vasculitis'. All patients will be treated with rituximab and steroids and we anticipate that most will respond well. If their disease is under reasonable control after four months, further treatment with either rituximab (a single dose ever four months for two years) or azathioprine tablets will be chosen randomly. The patients in the rituximab and azathioprine groups will then be compared. Patients will be in the trial for four years.
The study has been designed by members of the European Vasculitis Study group (EUVAS) and the Vasculitis Clinical Research Consortium (VCRC). It will include 190 participants from 30 hospitals in Europe, the USA, Australia and Mexico.
RITAZAREM is being funded by Arthritis Research UK, the U.S. National Institutes of Health and by Roche/Genentech.
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
|Study Design:||Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||An International, Open Label, Randomised Controlled Trial Comparing Rituximab With Azathioprine as Maintenance Therapy in Relapsing ANCA-associated Vasculitis|
- Time to relapse [ Time Frame: Any patients who have not relapsed at up to a maximum of 4 years will be censored. ] [ Designated as safety issue: No ]The primary endpoint is the time to disease relapse (either minor or major relapse) from randomisation.
- Remission at 24 and 48 months [ Time Frame: 24 and 48 months ] [ Designated as safety issue: No ]Proportion of patients who maintain remission at 24 and 48 months
- Combined damage assessment score [ Time Frame: Assessed at months 0, 4, 12, 24, 36 ] [ Designated as safety issue: No ]Cumulative accrual of damage as measured by the combined damage assessment score (CDA)
- Health-related quality of life [ Time Frame: Assessed at months 0, 4, 12, 24, 36 ] [ Designated as safety issue: No ]Health-related quality of life as measured using SF-36
- Cumulative GC exposure [ Time Frame: Up to 4 years ] [ Designated as safety issue: No ]Cumulative glucocorticoid (GC) exposure during the trial
- Severe adverse event rate [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]Severe adverse event (SAE) rate
- Infection rates [ Time Frame: Up to 4 years ] [ Designated as safety issue: Yes ]Infection (treated with intravenous or oral antibiotics) rates
|Study Start Date:||April 2013|
|Estimated Study Completion Date:||December 2016|
|Estimated Primary Completion Date:||December 2016 (Final data collection date for primary outcome measure)|
Experimental: Rituximab Maintenance
Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper
Rituximab IV infusion 1000 mg x 1 dose at months 4, 8, 12, 16 and 20 and glucocorticoids. Four - six hour infusion. Treatment with rituximab will cease at month 20.
Active Comparator: Azathioprine Maintenance
Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation). Azathioprine withdrawn at month 27.
Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27.
The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily.
If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.
Other Name: Imuran
Patients will be recruited at the time of relapse. All will receive rituximab 375 mg/m2/week x 4 and glucocorticoids.
Those patients that achieve disease control (BVAS/WG ≤ 1 and daily prednisone dose ≤ 10 mg) by month 4 will be randomised to the rituximab or control remission maintenance groups.
Treatment is protocolised for the entire duration of the study, until the common close date, when the final patient recruited has completed 36 months within the study or until the patient has completed 48 months on study whichever the sooner. Patients in the rituximab arm will receive treatment until month 20, and those in the azathioprine arm until month 27.
|Contact: David Jayneemail@example.com|
|Contact: Michelle Lewinfirstname.lastname@example.org|
|United States, Pennsylvania|
|University of Pennsylvania||Recruiting|
|Philadelphia, Pennsylvania, United States, 19104|
|Contact: Peter Merkel, MD 215-614-4401 email@example.com|
|Contact: Carol McAlear, MA 1-781-321-4567 firstname.lastname@example.org|
|Principal Investigator: Peter Merkel, MD|
|Cambridge, United Kingdom, CB2 0QQ|
|Contact: Michelle Lewin email@example.com|
|Principal Investigator: David Jayne|
|Study Chair:||David Jayne||Cambridge University Hospitals NHS Foundation Trust|
|Study Chair:||Peter Merkel||University of Pennsylvania|