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

Microscopic Polyangiitis (MPA) Clinical Trial

Official title:

Plasma Exchange and Glucocorticoid Dosing in the Treatment of Anti-neutrophil Cytoplasm Antibody Associated Vasculitis: an International Randomized Controlled Trial [Glucocorticoids]

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03919825
• Other study ID #: 5524
• Status: Completed
• Phase: Phase 3
• Start date: May 2010
• Est. completion date: August 31, 2017

Study information

• Verified date: April 2019
• Source: University of Pennsylvania
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 704
• Est. completion date: August 31, 2017
• Est. primary completion date: August 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 15 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Granulomatosis with Polyangiitis
• Granulomatosis With Polyangiitis (Wegener's) (GPA)
• Microscopic Polyangiitis
• Microscopic Polyangiitis (MPA)
• Systemic Vasculitis
• Vasculitis

Intervention

Drug:
• Glucocorticoids - Standard Dose
Subjects will receive glucocorticoids at a standard dose and will decrease following a standard regimen.
• Glucocorticoids - Reduced Dose
Subjects' will receive glucocorticoids at a reduced dose and will decrease following a reduced dose regimen

Locations

Country	Name	City	State
n/a

Sponsors (1)

Lead Sponsor	Collaborator
University of Pennsylvania

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Composite of i) all-cause mortality or ii) End-stage renal disease		2 years after the final subject is enrolled

External Links

•   PEXIVAS: Plasma Exchange listing