Low-dose Glucocorticoid Vasculitis Induction Study
Low-dose Glucocorticoid Vasculitis Induction Study
Previous reports suggested conventional immunosuppressants such as cyclophosphamide could not
 reduce glucocorticoid dose in remission induction in ANCA-associated vasculitis because of
 lower remission rate and higher relapse rate. However those reports didn't include rituximab.

 B cell depletion therapy by rituximab is a new strategy for remission induction in
 ANCA-associated vasculitis. The RAVE and RITUXVAS trial (NEJM 2010, both) showed high-dose
 glucocorticoid plus rituximab had roughly the same efficacy and safety as high-dose
 glucocorticoid plus IV-cyclophosphamide. In addition, recent retrospective observational
 studies reported low-dose glucocorticoid plus rituximab led to re-induction in severe
 relapsing ANCA-associated vasculitis.

 Thus, the investigators aim to investigate whether rituximab can reduce glucocorticoid dose
 in induction remission in ANCA-associated vasculitis (to show non-inferiority for efficacy
 between low-dose and high-dose glucocorticoid plus rituximab). Participants will be
 randomised to the "low-dose glucocorticoid plus rituximab" or the high-dose glucocorticoid
 plus rituximab" groups. Primary endpoint is proportion of remission at 6 months, then data
 regarding relapse and long-term safety will be collected until 24 months.

 The study has been designed by the principal and coordinating investigators. It will include
 140 participants from 18 hospitals in Japan. It is funded by Chiba University Hospital and
 Chiba East Hospital.
ANCA (anti-neutrophil cytoplasmic antibody)-associated vasculitis is characterised by small
 vessel vasculitis and presence of autoantibodies, ANCA. It can be a life-threatening disease
 with renal/respiratory failure. Current standard therapy in induction remission for
 ANCA-associated vasculitis is combination of high-dose glucocorticoid and
 IV-cyclophosphamide. This regimen is effective (remission rate; 80-90%), but often cause
 various glucocorticoid-related side effects. Especially, infection is related to death. Thus
 a new regimen reducing glucocorticoid dose is required.
Inclusion Criteria:

 1. Provision of written informed consent by a patient or a surrogate decision maker

 2. Age=>20 years

 3. New clinical diagnosis of ANCA-associated vasculitis (granulomatosis with
 polyangiitis, microscopic polyangiitis or renal limited ANCA-associated vasculitis)
 consistent with the 2012 Chapel Hill consensus definitions

 4. Positive test by ELISA for proteinase 3-ANCA or myeloperoxidase-ANCA

 Exclusion Criteria:

 1. Prior treatment for ANCA-associated vasculitis before trial entry

 2. ANCA-associated vasculitis related glomerulonephritis (eGFR<15ml/min) or alveolar
 hemorrhage (oxygen inhalation >2L/min)

 3. Presence of another multisystem autoimmune disease

 4. Known infection with HIV; a past or current history of hepatitis B virus or hepatitis
 C virus infection

 5. Desire to bear children, pregnancy or lactating

 6. History of malignancy within the past 5 years or any evidence of persistent malignancy

 7. Ongoing or recent (last 1 year) evidence of active tuberculosis

 8. Severe allergy or anaphylaxis to monoclonal antibody therapy

 9. Any concomitant condition anticipated to likely require oral systemic glucocorticoids,
 immunosuppressants, biologics, plasma exchange or IVIg

 10. Any biological B cell depleting agent (such as rituximab or belimumab) within the past
 6 months

 11. Other conditions, in the investigator's opinion, inappropriate for the trial entry