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

Last updated: N/A
Sponsor: University of Pennsylvania
Overall Status: Completed

Phase

3

Condition

Lupus

Vascular Diseases

Collagen Vascular Diseases

Treatment

N/A

Clinical Study ID

NCT03919825
5524
  • Ages > 15
  • All Genders

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

• New or previous clinical diagnosis of granulomatosis with polyangiitis or microscopicpolyangiitis 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 activeurine sediment characterized by glomerular haematuria or red cell casts andproteinuria AND

  • eGFR <50 ml/min/1.73 m2

  1. 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

  1. At least one of the following:

  • Evidence of alveolar hemorrhage on bronchoscopic examination or increasinglybloody 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

Exclusion Criteria:

  • A diagnosis of vasculitis other than granulomatosis with polyangiitis or microscopicpolyangiitis

  • Positive anti-glomerular basement membrane antibody test or renal biopsy demonstratinglinear glomerular immunoglobulin deposition

  • Receipt of dialysis for >21 days immediately prior to randomization or prior renaltransplant

  • 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 cyclophosphamideand/or >14 days of prednisone/prednisolone (>30 mg/day) and/or >1 dose of rituximabwithin the 28 days immediately prior to randomization

  • A comorbidity that, in the opinion of the investigator, precludes the use ofcyclophosphamide, glucocorticoids, or plasma exchange or absolutely mandates the useof plasma exchange

Study Design

Total Participants: 704
Study Start date:
May 01, 2010
Estimated Completion Date:
August 31, 2017

Study Description

Granulomatosis with polyangiitis (Wegener's) (WG) and microscopic polyangiitis (MPA) are syndromes of primary systemic vasculitis associated with anti-neutrophil cytoplasm antibodies (ANCA). Together, these syndromes are grouped as ANCA-associated systemic vasculitis (AAV).

Plasma exchange, a method of rapidly removing potentially pathogenic ANCA and other mediators of inflammation and coagulation, has shown promise as an adjunctive therapy in AAV to improve early disease control and improve rates of renal recovery in severe disease. Glucocorticoids (steroids) are a standard of care in the treatment of AAV. High doses of glucocorticoids early in disease, although reduce disease activity due to their anti-inflammatory and immunosuppressive properties, also increase the risk of infection, particularly in the elderly and in the presence of uremia. There is no randomized trial data to guide glucocorticoids dosing.

Patients with severe new or relapsing AAV and pulmonary hemorrhage and/or renal disease will be eligible for this trial.

Subjects participating in this study will be randomized to receive one of the following groups;

  1. Plasma exchange - 7 exchanges and, either standard or low-dose glucocorticoids or

  2. No plasma exchange and, either standard or low-dose glucocorticoids

All studies will receive standard remission-induction therapy with either cyclophosphamide or rituximab.