Clinical Trial: Low-dose Glucocorticoid Vasculitis Induction Study

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Low-dose Glucocorticoids Plus Rituximab Versus High-dose Glucocorticoids Plus Rituximab for Remission Induction in ANCA-associated Vasculitis; a Multicentre, Open Label, R

Brief 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.


Detailed Summary: 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.
Sponsor: Chiba University

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

Remission; BVAS ver.3=0 (or 1 with only one minor and persistent BVAS item) and prednisolone <10mg/day


Original Primary Outcome: Same as current

Current Secondary Outcome:

  • Time to remission [ Time Frame: assessed at 1, 2, 4 and 6 months ]
  • Overall survival, disease free survival, time to end-stage renal disease, time to the first serious adverse event [ Time Frame: 0-24 months ]
  • Proportions of death, relapse, end-stage renal disease and the composite of these [ Time Frame: at 6 and 24 months ]
  • Proportions of severe relapse [ Time Frame: at 24 months ]
  • Birmingham Vasculitis Activity Score (BVAS) version 3 [ Time Frame: assessed at 0, 1, 2, 4, 6, 9, 12, 18 and 24 months ]
    BVAS is a scoring system for assessing disease activity of vasculitis
  • Vasculitis Damage Index (VDI) [ Time Frame: assessed at 0, 6, 12, 18 and 24 months ]
    VDI is a scoring system for assessing irreversible disease damage due to vasculitis
  • Short-Form 36 (SF-36) [ Time Frame: assessed at 0, 6, 12, 18 and 24 months ]
    SF-36 is a scoring system for assessing patient QOL.
  • Patient global assessment (visualised analogue scale) [ Time Frame: assessed at 0, 6, 12, 18 and 24 months ]
  • Accumulative dose of glucocorticoids [ Time Frame: assessed at 6 and 24 months ]
  • Numbers of events of adverse events/serious adverse events, proportions of the patients with adverse events/serious adverse events [ Time Frame: at 6 and 24 months ]
  • Proportions of the patients with new onset diabetes mellitus [ Time Frame: at 6 and 24 months ]
  • Proportion of the patients with new onset insomnia [ Time Frame: at 6 and 24 months ]
  • Proportion of the patients with new onset bone fracture, bone density [ Time Frame: at 6 and 24 months ]
  • Number of infections, proportions of the patients with infection [ Time Frame: at 6 and 24 months ]
  • Proportions of the patients with new onset hypertension [ Time Frame: at 6 and 24 months ]
  • Proportions of the patients with new onset hyperlipidemia [ Time Frame: at 6 and 24 months ]
  • Proportions of patients achieving remission and discontinuance of glucocorticoids [ Time Frame: at 6 and 24 months ]
    Remission is BVAS ver3=0 and prednisolone <10mg/day.


Original Secondary Outcome:

  • Time to remission [ Time Frame: assessed at 1, 2, 4 and 6 months ]
  • Overall survival, disease free survival, time to end-stage renal disease, time to the first serious adverse event [ Time Frame: 0-24 months ]
  • Proportions of death, relapse, end-stage renal disease and the composite of these [ Time Frame: at 6 and 24 months ]
  • Proportions of severe relapse [ Time Frame: at 24 months ]
  • Birmingham Vasculitis Activity Score (BVAS) version 3 [ Time Frame: assessed at 0, 1, 2, 4, 6, 9, 12, 18 and 24 months ]
    BVAS is a scoring system for assessing disease activity of vasculitis
  • Vasculitis Damage Index (VDI) [ Time Frame: assessed at 0, 6, 12, 18 and 24 months ]
    VDI is a scoring system for assessing irreversible disease damage due to vasculitis
  • Short-Form 36 (SF-36) [ Time Frame: assessed at 0, 6, 12, 18 and 24 months ]
    SF-36 is a scoring system for assessing patient QOL.
  • Patient global assessment (visualised analogue scale) [ Time Frame: assessed at 0, 6, 12, 18 and 24 months ]
  • Accumulative dose of glucocorticoids [ Time Frame: assessed at 6 and 24 months ]
  • Numbers of events of adverse events/serious adverse events, proportions of the patients with adverse events/serious adverse events [ Time Frame: at 6 and 24 months ]
  • Proportions of the patients with new onset diabetes mellitus [ Time Frame: at 6 and 24 months ]
  • Proportion of the patients with new onset insomnia [ Time Frame: at 6 and 24 months ]
  • Proportion of the patients with new onset bone fracture, bone density [ Time Frame: at 6 and 24 months ]
  • Number of infections, proportions of the patients with infection [ Time Frame: at 6 and 24 months ]
  • Proportions of the patients with new onset hypertension [ Time Frame: at 6 and 24 months ]
  • Proportions of the patients with new onset hyperlipidemia [ Time Frame: at 6 and 24 months ]


Information By: Chiba University

Dates:
Date Received: July 18, 2014
Date Started: October 2014
Date Completion: September 2019
Last Updated: July 25, 2016
Last Verified: July 2016