RecruitingPhase 3NCT06983821

Safe Effective Therapy With Low-Dose Glucocorticoid in ANCA-Associated Vasculitis (SAFE-LOW)

Safe Effective Therapy With Low-Dose Glucocorticoid in ANCA-Associated Vasculitis (SAFE-LOW) Trial


Sponsor

Ottawa Hospital Research Institute

Enrollment

36 participants

Start Date

Nov 10, 2025

Study Type

INTERVENTIONAL

Conditions

Summary

The purpose of this study is to determine the safety and efficacy of a therapeutic regimen consisting of 4 weeks of glucocorticoids given with a combination of the usual induction agents for ANCA-associated vasculitis. The trial will compare this regimen to the current standard of care treatment and glucocorticoid dosing for ANCA-associated vasculitis with severe kidney involvement. This trial will begin as a pilot to assess feasibility of recruitment and of adherence to the intervention.


Eligibility

Min Age: 18 Years

Inclusion Criteria5

  • New diagnosis of, or relapse of, granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA), consistent with Chapel-Hill consensus definitions
  • Positive ELISA test for anti-meyloperoxidase (MPO) or anti-proteinase 3 (PR3)
  • Severe kidney involvement from active AAV, characterised by both of the following:
  • eGFR \< 40ml/min/1.73m2 (Patients known to have a stable eGFR \<40 ml/min/1.73m2 for \>3 months prior to enrollment are NOT eligible)
  • Biopsy proven at least focal necrotizing/crescentic glomerulonephritis OR active urinary sediment by microscopy (greater than or equal to 10 red blood cells \[RBC\]/high power field with erythrocyte casts or greater than or equal to 20% dysmorphic RBCs or greater than or equal to 5% acanthocytes without an alternative cause.

Exclusion Criteria11

  • A diagnosis of vasculitis other than GPA or MPA (including eosinophilic granulomatosis with polyangiitis, IgA vasculitis, cryoglobulinemic vasculitis, rheumatoid vasculitis)
  • Positive anti-glomerular basement membrane antibody test or renal biopsy demonstrating linear glomerular immunoglobulin deposition
  • A diagnosis of systemic lupus erythematosus or Sjögren's syndrome
  • Receipt of dialysis for \>21 days immediately prior to randomization or prior renal transplant
  • Age \<18
  • Pregnant at time of screening
  • Treatment with \>1 IV dose of CYC and/or \>14 days PO CYC and/or \>14 days of prednisone/prednisone (less than or equal to 30mg/day) and/or \>1 dose of RTX within the 28 days immediately prior to randomization
  • Chronic viral infection: HIV. HBV or HCV
  • Untreated latent mycobacterium tuberculosis infection
  • Active infection at time of presentation
  • A comorbidity or condition that, in the opinion of the investigator, precludes the use of GC, CYC or RTX

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Interventions

DRUGCyclophosphamide

IV Cyclophosphamide 15mg/kg/dose (age and eGFR adjusted), 2 doses 2 weeks apart

DRUGStandard of Care (SOC)

Participants will receive standard of care induction agent and glucocorticoid taper, at investigator discretion

DRUGPrednisone

4 weeks prednisone taper

DRUGRituximab (R)

Rituximab infusions, dosing and schedule at clinician/investigator discretion


Locations(2)

St-Joseph's Hospital

Hamilton, Ontario, Canada

The Ottawa Hospital

Ottawa, Ontario, Canada

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NCT06983821


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