Plasma Exchange for Renal Vasculitis

Microscopic Polyangiitis Clinical Trial

— MEPEX  

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01408836
• Other study ID #: BMH4-CT97-2328
• Status: Terminated
• Phase: Phase 2/Phase 3
• First received: August 2, 2011
• Last updated: August 2, 2011
• Start date: March 1995
• Est. completion date: December 2003

Study information

• Verified date: July 2011
• Source: Cambridge University Hospitals NHS Foundation Trust
• Contact: n/a
• Is FDA regulated: No
• Health authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 150
• Est. completion date: December 2003
• Est. primary completion date: June 2003
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 80 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Microscopic Polyangiitis
• Systemic Vasculitis
• Vasculitis
• Wegener Granulomatosis
• Wegener's Granulomatosis

Intervention

Procedure:
• Plasma exchange
Plasma exchange

Drug:
• Intravenous methyl prednisolone
Intravenous methyl prednisolone
• Methyl prednisolone
methyl prednisolone

Locations

Country	Name	City	State
United Kingdom	Addenbrooke's Hospital	Cambridge

Sponsors (9)

Lead Sponsor	Collaborator
Cambridge University Hospitals NHS Foundation Trust	Fundacio Clinic, Helsinki University, Imperial College London, London North West Healthcare NHS Trust, Lund University Hospital, University Hospital Birmingham, University Hospitals, Leicester, University Medical Center Groningen

Country where clinical trial is conducted

United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Renal recovery		Three months	No
Secondary	End stage renal disease at 12 months		12 months	No
Secondary	Serum creatinine at 12 months		12 months	No
Secondary	Severe adverse events		12 months	Yes

External Links

•   EUVAS homepage