Plasma Exchange for Renal Vasculitis (MEPEX)

Study Description

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Brief 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.

Condition or disease	Intervention/treatment	Phase
Wegener's Granulomatosis; Microscopic Polyangiitis	Procedure: Plasma exchange; Drug: Intravenous methyl prednisolone; Drug: Methyl prednisolone	Phase 2; Phase 3

Detailed 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.

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	150 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	None (Open Label)
Primary Purpose:	Treatment
Official Title:	Randomised Trial of Plasma Exchange or High Dose Methyl Prednisolone as Adjunctive Therapy for Severe Renal Vasculitis
Study Start Date :	March 1995
Actual Primary Completion Date :	June 2003
Actual Study Completion Date :	December 2003

Arms and Interventions

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm	Intervention/treatment
Experimental: 1; Plasma exchange x 7 over 14 days	Procedure: Plasma exchange; Plasma exchange
Active Comparator: 2; Methyl prednisolone 1g x 3	Drug: Intravenous methyl prednisolone; Intravenous methyl prednisolone Drug: Methyl prednisolone; methyl prednisolone

Outcome Measures

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Primary Outcome Measures :

1. Renal recovery [ Time Frame: Three months ]

Secondary Outcome Measures :

1. End stage renal disease at 12 months [ Time Frame: 12 months ]
2. Serum creatinine at 12 months [ Time Frame: 12 months ]
3. Severe adverse events [ Time Frame: 12 months ]

Eligibility Criteria

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Ages Eligible for Study:	18 Years to 80 Years (Adult, Senior)
Sexes Eligible for Study:	All
Accepts Healthy Volunteers:	No

Criteria

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.

Contacts and Locations

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Locations

United Kingdom
Addenbrooke's Hospital
Cambridge, United Kingdom, CB22QQ

Sponsors and Collaborators

Cambridge University Hospitals NHS Foundation Trust

University Hospital Birmingham

Imperial College London

London North West Healthcare NHS Trust

University Hospitals, Leicester

Lund University Hospital

University Medical Center Groningen

Fundacio Clinic

Helsinki University

Investigators

Study Director:	Niels Rasmussen, MD	Righospitalet, Copenhagen, Denmark

More Information

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Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Additional Information:

EUVAS homepage 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Walsh M, Casian A, Flossmann O, Westman K, Höglund P, Pusey C, Jayne DR; European Vasculitis Study Group (EUVAS). Long-term follow-up of patients with severe ANCA-associated vasculitis comparing plasma exchange to intravenous methylprednisolone treatment is unclear. Kidney Int. 2013 Aug;84(2):397-402. doi: 10.1038/ki.2013.131. Epub 2013 Apr 24.

ClinicalTrials.gov Identifier:	NCT01408836 History of Changes
Other Study ID Numbers:	BMH4-CT97-2328
First Posted:	August 3, 2011
Last Update Posted:	August 3, 2011
Last Verified:	July 2011

Keywords provided by Cambridge University Hospitals NHS Foundation Trust:

Vasculitis; ANCA; Therapy; Plasma exchange; Immunosuppression

Additional relevant MeSH terms:

Vasculitis; Systemic Vasculitis; Granulomatosis with Polyangiitis; Microscopic Polyangiitis; Vascular Diseases; Cardiovascular Diseases; Lung Diseases, Interstitial; Lung Diseases; Respiratory Tract Diseases; Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis; Autoimmune Diseases; Immune System Diseases; Cerebral Small Vessel Diseases; Cerebrovascular Disorders; Brain Diseases

Central Nervous System Diseases; Nervous System Diseases; Prednisolone acetate; Methylprednisolone acetate; Prednisolone; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone hemisuccinate; Prednisolone phosphate; Anti-Inflammatory Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Physiological Effects of Drugs; Antineoplastic Agents, Hormonal