Low-dose steroid treatment with standard induction medicines for ANCA-associated vasculitis affecting the kidneys
Safe Effective Therapy With Low-Dose Glucocorticoid in ANCA-Associated Vasculitis (SAFE-LOW) Trial
This trial will test whether giving only 4 weeks of steroids together with usual induction medicines (cyclophosphamide or rituximab) helps people with ANCA-associated vasculitis that has severely affected the kidneys while reducing steroid-related harms.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 36 (estimated) |
| Ages | 18 Years and up |
| Sex | All |
| Sponsor | Ottawa Hospital Research Institute Academic / other |
| Drugs / interventions | prednisone, rituximab, cyclophosphamide |
| Locations | 2 sites (Hamilton, Ontario and 1 other locations) |
| Trial ID | NCT06983821 on ClinicalTrials.gov |
What this trial studies
SAFE-LOW compares a short, fixed 4-week glucocorticoid regimen given with standard induction therapy (cyclophosphamide or rituximab) against the current longer steroid taper used for ANCA-associated vasculitis with severe kidney involvement. Adults with new or relapsing granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA) who are MPO- or PR3-positive and meet strict kidney criteria will be enrolled. The trial begins as a pilot to test feasibility of recruitment and adherence, then proceeds in a randomized phase 3 design to measure safety and effectiveness. Key outcomes include remission rates, kidney function, and steroid-related complications such as infections.
Who should consider this trial
Good fit: Adults with new or relapsing MPO- or PR3-positive GPA or MPA who have severe active kidney disease (eGFR <40 ml/min/1.73 m2 with biopsy-proven necrotizing/crescentic glomerulonephritis or defined active urinary sediment) are the intended participants.
Not a fit: People with other types of vasculitis, those without severe active kidney involvement, or patients with a chronic stable low eGFR for more than three months are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, it could control vasculitis while lowering serious steroid side effects such as infections and other toxicities.
How similar studies have performed: Prior large trials such as PEXIVAS, LOVAS, and ADVOCATE showed that reduced steroid regimens or steroid-sparing approaches can be effective in AAV, but questions remain specifically for patients with severe kidney involvement.
Eligibility criteria
Show full inclusion / exclusion criteria
* 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 Criteria (any of the following) * 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
Where this trial is running
Hamilton, Ontario and 1 other locations
- St-Joseph's Hospital — Hamilton, Ontario, Canada (Not_yet_recruiting)
- The Ottawa Hospital — Ottawa, Ontario, Canada (Recruiting)
Study contacts
- Principal investigator: David Massicotte-Azarniouch, MD, MSc — The Ottawa Hospital
- Study coordinator: David Massicotte-Azarniouch, MD, MSc
- Email: damassicotte@toh.ca
- Phone: 613-738-8400
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.