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

ConditionsGranulomatosis With PolyangiitisMicroscopic Polyangiitis (MPA)
Trial statusRecruiting
Trial phasePhase 3
Trial typeInterventional
Biological sexAll
Age18+
SponsorOttawa Hospital Research Institute

About this trial

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 criteria

This trial does not accept healthy volunteers

Qualifiers

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)

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.

Disqualifiers

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

Trial design

Design model

Parallel

Treatments tested in this trial

  • Cyclophosphamide

    Drug

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

  • Standard of Care (SOC)

    Drug

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

  • Prednisone

    Drug

    4 weeks prednisone taper

  • Rituximab (R)

    Drug

    Rituximab infusions, dosing and schedule at clinician/investigator discretion

Treatment groups

36 Participants
are divided into 2 treatment groups
Group A: Intervention ArmExperimental treatment 3 interventions
Group B: Standard of careActive comparator 1 intervention

Trial outcomes

Primary outcomes

1

Pilot trial: percent adherence to intervention regimen

Pilot trial: percent adherence in the intervention arm (non-adherence will be defined as the use of more than 25% of the total expected oral prednisone in the intervention arm at 12 weeks)

Time frame
12 weeks
2

Full-scale trial: Rate of serious infection

Full-scale trial: rate of serious infection (Infection occurring after randomisation requiring IV antibiotics, or leading to hospitalisation or death)

Time frame
26 weeks

Secondary outcomes

1

Pilot trial: recruitment rate

Pilot trial: recruitment rate measured as incidence rate based on randomised participants/centre-month

Time frame
52 weeks
2

Full-scale trial: Remission rate

Full-scale trial: Remission defined as absence of manifestations due to active AAV. Remission status will be determined at study visits based on clinician judgement. If a participant is not in remission at an assessment point, the affected organ system (based on Birmingham Vasculitis Activity Score \[BVAS\]) will be captured. If a participant is transitioned to or being planned for maintenance therapy at their study visit, then they will also be considered to have achieved remission.

Time frame
26 weeks

Other outcomes

1

End-stage kidney disease rate

At least 12 continuous weeks of new requirement of kidney replacement therapy

Time frame
26 and 52 weeks
2

Change in eGFR

Change in eGFR compared to baseline

Time frame
26 and 52 weeks
3

Death

Death rate

Time frame
26 and 52 weeks
4

Remission

Remission rate

Time frame
12, 26 and 52 weeks

Sponsors and contacts

Click on the lead sponsor to view all of their trials.

Ottawa Hospital Research Institute

Lead sponsor

Source ClinicalTrials.gov
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