Plasma Exchange and Glucocorticoids for Treatment of Anti-Neutrophil Cytoplasm Antibody (ANCA) - Associated Vasculitis

Overview

About this study

The purpose of this study is to determine whether plasma exchange as well as immunosuppressive therapy are effective in reducing death and end-stage renal disease (ESRD). The trial will also study whether a reduced cumulative dosing regimen of glucocorticoids is as effective as a standard disease regimen.

The FDA-OOPD is one of the funding sources for this study.

Participation eligibility

Participant eligibility includes age, gender, type and stage of disease, and previous treatments or health concerns. Guidelines differ from study to study, and identify who can or cannot participate. There is no guarantee that every individual who qualifies and wants to participate in a trial will be enrolled. Contact the study team to discuss study eligibility and potential participation.

Inclusion Criteria:

• New or previous clinical diagnosis of granulomatosis with polyangiitis or microscopic polyangiitis consistent with the Chapel-Hill consensus definitions AND • Positive test for proteinase 3-ANCA or myeloperoxidase-ANCA AND

Severe vasculitis defined by at least one of the following:
1. Renal involvement with both:
  - Renal biopsy demonstrating focal necrotizing glomerulonephritis or active urine sediment characterized by glomerular haematuria or red cell casts and proteinuria
  AND
  - eGFR <50 ml/min/1.73 m2
2. Pulmonary hemorrhage due to active vasculitis defined by:
  - A compatible chest x-ray or CT scan (diffuse pulmonary infiltrates)
  AND
  - The absence of an alternative explanation for all pulmonary infiltrates (e.g. volume overload or pulmonary infection)
  AND
3. At least one of the following:
  - Evidence of alveolar hemorrhage on bronchoscopic examination or increasingly bloody returns with bronchoalveolar lavage
  - Observed hemoptysis
  - Unexplained anemia (<10 g/dL) or documented drop in hemoglobin >1 g/dL)
  - Increased diffusing capacity of carbon dioxide
Provision of informed consent by patient or a surrogate decision maker

Exclusion Criteria:

A diagnosis of vasculitis other than granulomatosis with polyangiitis or microscopic polyangiitis
Positive anti-glomerular basement membrane antibody test or renal biopsy demonstrating linear glomerular immunoglobulin deposition
Receipt of dialysis for >21 days immediately prior to randomization or prior renal transplant
Age <15 years
Pregnancy
Inability or unwillingness to comply with birth control/abstinence
Treatment with >1 IV dose of cyclophosphamide and/or >14 days of oral cyclophosphamide and/or >14 days of prednisone/prednisolone (>30 mg/day) and/or >1 dose of rituximab within the 28 days immediately prior to randomization
A comorbidity that, in the opinion of the investigator, precludes the use of cyclophosphamide, glucocorticoids, or plasma exchange or absolutely mandates the use of plasma exchange

Participating Mayo Clinic locations

Study statuses change often. Please contact the study team for the most up-to-date information regarding possible participation.

Mayo Clinic Location	Status
Rochester, Minn. Mayo Clinic principal investigator Ulrich Specks, M.D.	Closed for enrollment

Mayo Clinic Location

Status

Rochester, Minn.

Mayo Clinic principal investigator

Ulrich Specks, M.D.

Closed for enrollment

More information

Publications

Granulomatosis with polyangiitis (GPA, Wegener's) and microscopic polyangiitis (MPA) are small vessel vasculitides collectively referred to as anti-neutrophil cytoplasm antibody-associated vasculitis (AAV). AAV is associated with high rates of morbidity and mortality due to uncontrolled disease and treatment toxicity. Small randomized trials suggest adjunctive plasma exchange may improve disease control, while observational evidence suggests that current oral glucocorticoid doses are associated with severe infections in patients with AAV. A randomized study of both plasma exchange and glucocorticoids is required to evaluate plasma exchange and oral glucocorticoid dosing in patients with AAV. Read More on PubMed

Clinical Trials