Granulomatosis With PolyangiitisPhase 3SAFE-LOWNCT06983821
Safe Effective Therapy With Low-Dose Glucocorticoid in ANCA-Associated Vasculitis (SAFE-LOW)
A Phase 3 study testing Cyclophosphamide, Prednisone and Rituximab (R) in people with Granulomatosis With Polyangiitis and Microscopic Polyangiitis (MPA), run by Ottawa Hospital Research Institute at 2 sites in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Granulomatosis With Polyangiitis, Microscopic Polyangiitis (MPA)
- What is being tested?
- Cyclophosphamide, Prednisone and Rituximab (R)
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 36 participants
- Where
- 2 sitesCanada
- Study dates
- 10 Nov 2025to Feb 2029
- Phase
- Phase 3
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
Canada2 sites, 2 recruiting
- Not yet recruiting
St-Joseph's Hospital
Hamilton, Ontario
- Recruiting
The Ottawa Hospital
Ottawa, Ontario
About this study
Official title: Safe Effective Therapy With Low-Dose Glucocorticoid in ANCA-Associated Vasculitis (SAFE-LOW) 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.
Read the detailed description
ANCA-associated vasculitis (AAV) is an auto-immune disease which often involves the kidneys. It is a serious condition as it can lead to severe kidney impairment, often kidney failure, and may even be life-threatening. Current treatments, typically cyclophosphamide (CYC) or rituximab (RTX) with a tapering course of glucocorticoids (GC), allow most patients to achieve control of their disease (remission). Glucocorticoids are most often used initially at high doses, and then gradually decreased to low doses over at least 6 months. This leads to major treatment toxicities, notably infections and GC-related adverse events, major contributors to patient morbidity and mortality. Recent research has focused on finding ways to reduce treatment-related toxicities without compromising efficacy for controlling disease manifestations. This includes a reduced-dose GC taper for severe AAV from the Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis (PEXIVAS) trial, an even more reduced-dose GC taper in patients with moderate severity AAV from the Effect of Reduced-Dose vs High-Dose Glucocorticoids Added to Rituximab on Remission Induction in ANCA-Associated Vasculitis (LOVAS) trial, and a novel GC-sparing agent examined in the Avacopan for the Treatment of ANCA-Associated Vasculitis (ADVOCATE) trial. Despite these advances, patients still experience high rates of infections, one of the major causes of death in the first year after diagnosis, particularly in patients with most severe forms of disease. Also, novel GC-sparing drugs are costly and have limited availability throughout the world; patients who cannot access this get exposed to significant amounts of GC and must suffer their dreaded side effects.
This study addresses the unresolved issues of unacceptably high infection risk and of providing a widely available means of reducing GC exposure to minimise treatment side effects. The investigators will examine an induction treatment regimen for severe AAV consisting of 2 doses of IV CYC in combination with 4 weeks of GC and standard RTX. The control arm will be the current standard of care treatment for severe AAV. Non-controlled studies suggest the use of short duration CYC with RTX allows for minimisation of up-front GC use, as little as 1-2 weeks, but this needs to be tested in a prospective, controlled manner. The investigators hypothesize that the combination of CYC with standard RTX will allow less GC to be used for AAV. This study will begin as a pilot to examine the feasibility of the conducting the study, adherence to the intervention regimen, and of recruiting patients. If feasibility is demonstrated, the study will be extended to a full-scale trial.
- Being tested
- Cyclophosphamide, Standard of Care (SOC), Prednisone, Rituximab (R)
- Keywords
- ANCA-associated vasculitis, cyclophosphamide, glucoccorticoid, rituximab, vasculitis, granulomatosis with polyangiitis, microscopic polyangiitis, GPA, MPA
- Medical subject headings
- Granulomatosis with Polyangiitis, Microscopic Polyangiitis, Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Vasculitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CyclophosphamideDrug
Also called Cytoxan
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
PrednisoneDrug
4 weeks prednisone taper
Rituximab (R)Drug
Rituximab infusions, dosing and schedule at clinician/investigator discretion
| Study group | Role | What they receive |
|---|---|---|
| Intervention Arm | Experimental | IV Cyclophosphamide x 2 doses AND Rituximab AND Prednisone x 4 weeks Receives: Drug: Cyclophosphamide; Drug: Prednisone; Drug: Rituximab (R) |
| Standard of care | Active comparator | Participants in this arm receive standard of care treatment induction agent and glucocorticoid dose/duration, left to the discretion of the investigator Receives: Drug: Standard of Care (SOC) |
What is being measured
The primary outcome is the main question the study is designed to answer.
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)
Measured: 12 weeks
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)
Measured: 26 weeks
Secondary outcomes (2)
Pilot trial: recruitment rate
Pilot trial: recruitment rate measured as incidence rate based on randomised participants/centre-month
Measured: 52 weeks
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.
Measured: 26 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 May 2025
- Study start10 Nov 2025
- Primary completionFeb 2028 (estimated)
- Study completionFeb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Granulomatosis With PolyangiitisStudies of the same condition, open and under way.
- More trials run by Ottawa Hospital Research InstituteThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Open-label, randomised controlled trial
- Masking
- None (open label)
- Enrolment
- 36 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ottawa Hospital Research Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- David Massicotte-Azarniouch, MD, MSc, Principal investigator, The Ottawa Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06983821
- Sponsor's protocol ID
- 20250118-01T
- Acronym
- SAFE-LOW
- Status last verified
- Jan 2026
- First submitted
- 1 Apr 2025
- Last updated
- 30 Jan 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: As per institutional requirements on protection of private health information
Study at a glance
From the registry record, last updated by the sponsor on 30 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safe Effective Therapy With Low-Dose Glucocorticoid in ANCA-Associated Vasculitis (SAFE-LOW) Trial
- ClinicalTrials.gov ID
- NCT06983821
- Acronym / sponsor ID
- SAFE-LOW / 20250118-01T
- Keywords
- ANCA-associated vasculitis, cyclophosphamide, glucoccorticoid, rituximab, vasculitis, granulomatosis with polyangiitis, microscopic polyangiitis, GPA
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 36 participants (estimated)
- Lead sponsor
- Ottawa Hospital Research InstituteUniversity, hospital or other
- Study start
- 10 Nov 2025 (actual)
- Primary completion
- Feb 2028 (estimated)
- Study completion
- Feb 2029 (estimated)
- First posted
- 21 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
ANCA-associated vasculitis (AAV) is an auto-immune disease which often involves the kidneys. It is a serious condition as it can lead to severe kidney impairment, often kidney failure, and may even be life-threatening. Current treatments, typically cyclophosphamide (CYC) or rituximab (RTX) with a tapering course of glucocorticoids (GC), allow most patients to achieve control of their disease (remission). Glucocorticoids are most often used initially at high doses, and then gradually decreased to low doses over at least 6 months. This leads to major treatment toxicities, notably infections and GC-related adverse events, major contributors to patient morbidity and mortality. Recent research has focused on finding ways to reduce treatment-related toxicities without compromising efficacy for controlling disease manifestations. This includes a reduced-dose GC taper for severe AAV from the Plasma Exchange and Glucocorticoids in Severe ANCA-Associated Vasculitis (PEXIVAS) trial, an even more reduced-dose GC taper in patients with moderate severity AAV from the Effect of Reduced-Dose vs High-Dose Glucocorticoids Added to Rituximab on Remission Induction in ANCA-Associated Vasculitis (LOVAS) trial, and a novel GC-sparing agent examined in the Avacopan for the Treatment of ANCA-Associated Vasculitis (ADVOCATE) trial. Despite these advances, patients still experience high rates of infections, one of the major causes of death in the first year after diagnosis, particularly in patients with most severe forms of disease. Also, novel GC-sparing drugs are costly and have limited availability throughout the world; patients who cannot access this get exposed to significant amounts of GC and must suffer their dreaded side effects.
This study addresses the unresolved issues of unacceptably high infection risk and of providing a widely available means of reducing GC exposure to minimise treatment side effects. The investigators will examine an induction treatment regimen for severe AAV consisting of 2 doses of IV CYC in combination with 4 weeks of GC and standard RTX. The control arm will be the current standard of care treatment for severe AAV. Non-controlled studies suggest the use of short duration CYC with RTX allows for minimisation of up-front GC use, as little as 1-2 weeks, but this needs to be tested in a prospective, controlled manner. The investigators hypothesize that the combination of CYC with standard RTX will allow less GC to be used for AAV. This study will begin as a pilot to examine the feasibility of the conducting the study, adherence to the intervention regimen, and of recruiting patients. If feasibility is demonstrated, the study will be extended to a full-scale trial.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- Open-label, randomised controlled trial
| Arm | Type | Receives |
|---|---|---|
| Intervention Arm | Experimental | Drug: Cyclophosphamide, Drug: Prednisone, Drug: Rituximab (R)IV Cyclophosphamide x 2 doses AND Rituximab AND Prednisone x 4 weeks |
| Standard of care | Active comparator | Drug: Standard of Care (SOC)Participants in this arm receive standard of care treatment induction agent and glucocorticoid dose/duration, left to the discretion of the investigator |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CyclophosphamideAlso: CytoxanIV Cyclophosphamide 15mg/kg/dose (age and eGFR adjusted), 2 doses 2 weeks apart | Drug | Intervention Arm |
| Standard of Care (SOC)Participants will receive standard of care induction agent and glucocorticoid taper, at investigator discretion | Drug | Standard of care |
| Prednisone4 weeks prednisone taper | Drug | Intervention Arm |
| Rituximab (R)Rituximab infusions, dosing and schedule at clinician/investigator discretion | Drug | Intervention Arm |
Primary outcome
Pilot trial: percent adherence to intervention regimen
Time frame: 12 weeks
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)
Full-scale trial: Rate of serious infection
Time frame: 26 weeks
Full-scale trial: rate of serious infection (Infection occurring after randomisation requiring IV antibiotics, or leading to hospitalisation or death)
2 secondary outcomes
Pilot trial: recruitment rate
Time frame: 52 weeks
Full-scale trial: Remission rate
Time frame: 26 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Jan 2026.
- Individual participant dataSharing planned: No. As per institutional requirements on protection of private health information
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
David Massicotte-Azarniouch, MD, MSc principal investigator
The Ottawa Hospital
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Cyclophosphamide, Prednisone and Rituximab (R) in people with Granulomatosis With Polyangiitis and Microscopic Polyangiitis (MPA), run by Ottawa Hospital Research Institute at 2 sites in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 0 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Jan 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact David Massicotte-Azarniouch, MD, MSc (613-738-8400 ext. 82891, damassicotte@toh.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pilot trial: percent adherence to intervention regimen (time frame: 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Jan 2026.