A Phase 3 interventional study of Cyclophosphamide and Standard of Care (SOC) in Granulomatosis With Polyangiitis and Microscopic Polyangiitis (MPA), sponsored by Ottawa Hospital Research Institute. Recruiting at 2 sites in Canada. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-01-30.
Sponsored by Ottawa Hospital Research Institute · Phase 3, Interventional, and Treatment
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.
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.
104 studies on the registry are indexed under Granulomatosis with Polyangiitis; 16 are open to participants now.
This study's planned enrollment of 36 is below the median of 70 across 69 interventional studies indexed under Granulomatosis with Polyangiitis.
Browse Granulomatosis with Polyangiitis studies →Ottawa Hospital Research Institute is the lead sponsor of 547 studies on the registry; 99 are open to participants now.
Counted across the registry records on this site, refreshed daily.
Exclusion Criteria (any of the following)
Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
GFR and eGFR (kidney filtering)
GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².
Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Biopsy and archival tissue
A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.
Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
HIV
The human immunodeficiency virus, which weakens the immune system.
Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis B tests
Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.
Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
Hepatitis C tests
Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.
After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.
Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.
IV Cyclophosphamide x 2 doses AND Rituximab AND Prednisone x 4 weeks
Drug: Cyclophosphamide · Drug: Prednisone · Drug: Rituximab (R)
Participants in this arm receive standard of care treatment induction agent and glucocorticoid dose/duration, left to the discretion of the investigator
Drug: Standard of Care (SOC)
IV Cyclophosphamide 15mg/kg/dose (age and eGFR adjusted), 2 doses 2 weeks apart
Also known as: Cytoxan
Participants will receive standard of care induction agent and glucocorticoid taper, at investigator discretion
4 weeks prednisone taper
Rituximab infusions, dosing and schedule at clinician/investigator discretion
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
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
Pilot trial: recruitment rate
Pilot trial: recruitment rate measured as incidence rate based on randomised participants/centre-month
Time frame: 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.
Time frame: 26 weeks
End-stage kidney disease rate
At least 12 continuous weeks of new requirement of kidney replacement therapy
Time frame: 26 and 52 weeks
Change in eGFR
Change in eGFR compared to baseline
Time frame: 26 and 52 weeks
Death
Death rate
Time frame: 26 and 52 weeks
Remission
Remission rate
Time frame: 12, 26 and 52 weeks
Rate of remission without the need for rescue therapy
Use of medications outside of the described therapies in each arm for the treatment of disease activity due to active AAV (disease flare, resistant disease or sub-optimal disease control).
Time frame: 26 weeks
Rescue therapy
Need for rescue therapy (rate)
Time frame: 26 weeks
Health-related quality of life patient-reported outcome
AAV-PRO (ANCA-associated vasculitis patient reported outcome): domain scores, scale 0-100, higher scores represent greater severity
Time frame: 4 and 12 weeks
Serious infection
Serious infection rate
Time frame: 26 and 52 weeks
Infection
Rate of infection (any severity)
Time frame: 26 and 52 weeks
Serious adverse event
Serious adverse event rate
Time frame: 26 and 52 weeks
Glucocorticoid exposure
Cumulative oral and IV prednisone equivalent dose
Time frame: 26 and 52 weeks
Weight
weight change from baseline
Time frame: 12, 26 and 52 weeks
New onset diabetes
New HbA1c \>6.5%
Time frame: 26 and 52 weeks
Plan to share: No — As per institutional requirements on protection of private health information
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Studies of the drugs tested here: Cyclophosphamide · Prednisone · Rituximab
Granulomatosis with Polyangiitis →
Ottawa Hospital Research Institute →