Low-dose Glucocorticoid Vasculitis Induction Study

Sponsor
Chiba University
Study ID
NCT02198248
Phase
PHASE4
Status
Unknown

Conditions

  • Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
  • Microscopic Polyangiitis
  • Wegener Granulomatosis

Eligibility Criteria

Sex
ALL
Age
20 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Rituximab — DRUG
    Patients will be administered rituximab (375mg/m2/w x4 infusions) for reducing glucocorticoid dose in remission induction phase.
  • Glucocorticoids — DRUG
    "Low-dose" group commenced 0.5mg/kg/day, then taper and stop within 6 months following pre-defined schedule. "High-dose" group commenced 1.0mg/kg/day, then taper to 10mg/day within 6 months following pre-defined schedule.

Study Details

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.

Key Dates

Start date
Oct 31, 2014
Status verified
Jan 2021
Primary completion
Dec 31, 2019
Completion
Jun 30, 2021

Study Design

Enrollment
140 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Low-dose glucocorticoid
    Prednisolone will be commenced with dose of 0.5mg/kg/day and will be tapered and off within 6 months. If a patient fails to achieve BVAS=0, an investigator can postpone the procedure of stopping prednisolone (prednisolone 5mg/day x 2 weeks, 4mg/day x 2 weeks, 3mg/day x 4 weeks, 2mg/day x 4 weeks, 1mg/day x 4 weeks, then off prednisolone). Once starting the procedure, prednisolone must be off after 16 weeks. Patients will also receive rituximab (375mg/m2/w x4). After achieving remission, patients will be receive rituximab (1g/body or 0.5g/bodyx2) every 6 months as remission maintenance therapy.
  • Active Comparator: High-dose glucocorticoid
    Prednisolone will be commenced with dose of 1.0mg/kg/day and will be tapered to 10mg/day within 6 months. Patients will also receive rituximab (375mg/m2/w x4). After achieving remission, patients will be receive rituximab (1g/body or 0.5g/bodyx2) every 6 months as remission maintenance therapy. There's no limitation by the protocol regarding further prednisolone tapering.

Primary Outcome Measure

Proportion of the patients achieving remission [ Time Frame: 6 months ]

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