Clinical Trial: Rituximab Vasculitis Maintenance Study
Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional
Official Title: An International, Open Label, Randomised Controlled Trial Comparing Rituximab With Azathioprine as Maintenance Therapy in Relapsing ANCA-associated Vasculitis
Brief Summary:
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.
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.
Sponsor: Cambridge University Hospitals NHS Foundation Trust
Current Primary Outcome: Time to relapse [ Time Frame: Any patients who have not relapsed at up to a maximum of 4 years will be censored. ]
Original Primary Outcome: Same as current
Current Secondary Outcome:
- Remission at 24 and 48 months [ Time Frame: 24 and 48 months ]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 ]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 ]Health-related quality of life as measured using SF-36
- Cumulative GC exposure [ Time Frame: Up to 4 years ]Cumulative glucocorticoid (GC) exposure during the trial
- Severe adverse event rate [ Time Frame: Up to 4 years ]Severe adverse event (SAE) rate
- Infection rates [ Time Frame: Up to 4 years ]Infection (treated with intravenous or oral antibiotics) rates
Original Secondary Outcome: Same as current
Information By: Cambridge University Hospitals NHS Foundation Trust
Dates:
Date Received: August 31, 2012
Date Started: April 2013
Date Completion: December 2019
Last Updated: February 21, 2017
Last Verified: February 2017
