Low-dose Glucocorticoid Vasculitis Induction Study

• Status: Active, not recruiting
• Trial end date: 2021-06-01
• Target enrollment: 0
• Participant gender: All

Summary

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.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Chiba University
• Collaborator: National Hospital Organization Chiba East Hospital
• Treatments: Glucocorticoids; Methylprednisolone; Methylprednisolone acetate; Methylprednisolone Hemisuccinate; Prednisolone; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Rituximab

Criteria

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