Plasma Exchange for Renal Vasculitis

Study Overview
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Brief Summary
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The purpose of this study is to test whether additional therapy with plasma exchange improves the chances of kidney recovery in severe kidney vasculitis.

Detailed Description
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Primary systemic vasculitis associated with autoantibodies to neutrophil cytoplasmic antigens (ANCA), is the most frequent cause of rapidly progressive glomerulonephritis. Renal failure at presentation often progresses to end stage renal disease despite immunosuppressive therapy. We investigated whether the addition of plasma exchange was more effective than intravenous (IV) methyl prednisolone in the achievement of renal recovery for ANCA associated systemic vasculitis presenting with a serum creatinine above 500umol/l (5.8mg/dl). 137 patients with a new diagnosis of ANCA associated systemic vasculitis, serum creatinine above 500umol/l (5.8mg/dl) and a renal biopsy demonstrating a focal, necrotizing glomerulonephritis were randomized to receive seven plasma exchanges or IV methyl prednisolone 1000mg/day for three days. Both groups were treated with cyclophosphamide and oral prednisolone. The primary end-point was dialysis independence with a serum creatinine below 500umol/l (5.8mg/dl) at three months. Secondary end-points included renal and patient survival at 12 months and severe adverse event rates.

Official Title
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Randomised Trial of Plasma Exchange or High Dose Methyl Prednisolone as Adjunctive Therapy for Severe Renal Vasculitis

Conditions
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Wegener's Granulomatosis, Microscopic Polyangiitis

Intervention / Treatment
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* Procedure: Plasma exchange
* Drug: Intravenous methyl prednisolone
* Drug: Methyl prednisolone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Diagnosis of Wegener's granulomatosis or microscopic polyangiitis, using criteria adapted by EUVAS from the disease definitions of the Chapel Hill consensus conference Biopsy proven, pauci-immune, necrotising and/or crescentic glomerulonephritis, in the absence of other defined glomerulopathy Severe renal impairment defined by: (i) oliguria (<400ml/24hr), or (ii) intention to commence dialysis within 48 hours of admission, and (iii) creatinine >500umol/l (5.8mg/dl). Exclusion Criteria: Age under 18 or over 80 years Inadequate contraception in women of child-bearing age Pregnancy Previous malignancy Hepatitis B antigenaemia, anti-hepatitis C virus or anti-human immunodeficiency virus antibody Diagnosis of Churg-Strauss syndrome, Henoch-Schönlein purpura, rheumatoid vasculitis, mixed essential cryoglobulinaemia or systemic lupus erythematosus Circulating anti-GBM antibodies or linear IgG staining of the GBM on renal biopsy Life-threatening non-renal manifestations of vasculitis, including alveolar hemorrhage requiring mechanical ventilation within 24 hours of admission On dialysis for > two weeks prior to entry Creatinine > 200umol/l (2.3mg/dl) one year or more before entry A second clearly defined cause of renal failure Previous episode of biopsy-proven necrotising and/or crescentic glomerulonephritis > two weeks treatment with cyclophosphamide or azathioprine > 500mg IV methyl prednisolone Plasma exchange within the preceding year > three months treatment with oral prednisolone Allergy to study medications.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 1<br>Plasma exchange x 7 over 14 days | Procedure: Plasma exchange<br>* Plasma exchange<br>|
| Active Comparator: 2<br>Methyl prednisolone 1g x 3 | Drug: Intravenous methyl prednisolone<br>* Intravenous methyl prednisolone<br>Drug: Methyl prednisolone<br>* methyl prednisolone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Renal recovery |  | Three months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| End stage renal disease at 12 months |  | 12 months | 
| Serum creatinine at 12 months |  | 12 months | 
| Severe adverse events |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ANCA, Therapy, Vasculitis, Plasma exchange, Immunosuppression