Plasma Exchange for Renal Vasculitis (MEPEX)

NHS Foundation Trust

Status and phase

Terminated

Phase 3

Phase 2

Conditions

Wegener's Granulomatosis

Microscopic Polyangiitis

Treatments

Drug: Methyl prednisolone

Procedure: Plasma exchange

Drug: Intravenous methyl prednisolone

Study type

Interventional

Funder types

Other

Identifiers

NCT01408836

BMH4-CT97-2328

Details and patient eligibility

About

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

Full description

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.

Enrollment

150 patients

Sex

All

Ages

18 to 80 years old

Volunteers

No Healthy Volunteers

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.