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Plasma Exchange for Renal Vasculitis (MEPEX)

Primary Purpose

Wegener's Granulomatosis, Microscopic Polyangiitis

Status
Terminated
Phase
Phase 2
Locations
United Kingdom
Study Type
Interventional
Intervention
Plasma exchange
Intravenous methyl prednisolone
Methyl prednisolone
Sponsored by
Cambridge University Hospitals NHS Foundation Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Wegener's Granulomatosis focused on measuring Vasculitis, ANCA, Therapy, Plasma exchange, Immunosuppression

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept 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.

Sites / Locations

  • Addenbrooke's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

1

2

Arm Description

Plasma exchange x 7 over 14 days

Methyl prednisolone 1g x 3

Outcomes

Primary Outcome Measures

Renal recovery

Secondary Outcome Measures

End stage renal disease at 12 months
Serum creatinine at 12 months
Severe adverse events

Full Information

First Posted
August 2, 2011
Last Updated
August 2, 2011
Sponsor
Cambridge University Hospitals NHS Foundation Trust
Collaborators
University Hospital Birmingham, Imperial College London, London North West Healthcare NHS Trust, University Hospitals, Leicester, Lund University Hospital, University Medical Center Groningen, Fundacio Clinic Barcelona, University of Helsinki
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1. Study Identification

Unique Protocol Identification Number
NCT01408836
Brief Title
Plasma Exchange for Renal Vasculitis
Acronym
MEPEX
Official Title
Randomised Trial of Plasma Exchange or High Dose Methyl Prednisolone as Adjunctive Therapy for Severe Renal Vasculitis
Study Type
Interventional

2. Study Status

Record Verification Date
July 2011
Overall Recruitment Status
Terminated
Why Stopped
Completed
Study Start Date
March 1995 (undefined)
Primary Completion Date
June 2003 (Actual)
Study Completion Date
December 2003 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Cambridge University Hospitals NHS Foundation Trust
Collaborators
University Hospital Birmingham, Imperial College London, London North West Healthcare NHS Trust, University Hospitals, Leicester, Lund University Hospital, University Medical Center Groningen, Fundacio Clinic Barcelona, University of Helsinki

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Wegener's Granulomatosis, Microscopic Polyangiitis
Keywords
Vasculitis, ANCA, Therapy, Plasma exchange, Immunosuppression

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2, Phase 3
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
150 (Actual)

8. Arms, Groups, and Interventions

Arm Title
1
Arm Type
Experimental
Arm Description
Plasma exchange x 7 over 14 days
Arm Title
2
Arm Type
Active Comparator
Arm Description
Methyl prednisolone 1g x 3
Intervention Type
Procedure
Intervention Name(s)
Plasma exchange
Intervention Description
Plasma exchange
Intervention Type
Drug
Intervention Name(s)
Intravenous methyl prednisolone
Intervention Description
Intravenous methyl prednisolone
Intervention Type
Drug
Intervention Name(s)
Methyl prednisolone
Intervention Description
methyl prednisolone
Primary Outcome Measure Information:
Title
Renal recovery
Time Frame
Three months
Secondary Outcome Measure Information:
Title
End stage renal disease at 12 months
Time Frame
12 months
Title
Serum creatinine at 12 months
Time Frame
12 months
Title
Severe adverse events
Time Frame
12 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility 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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Niels Rasmussen, MD
Organizational Affiliation
Righospitalet, Copenhagen, Denmark
Official's Role
Study Director
Facility Information:
Facility Name
Addenbrooke's Hospital
City
Cambridge
ZIP/Postal Code
CB22QQ
Country
United Kingdom

12. IPD Sharing Statement

Citations:
PubMed Identifier
23615499
Citation
Walsh M, Casian A, Flossmann O, Westman K, Hoglund 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.
Results Reference
derived
Links:
URL
http://www.vasculitis.org
Description
EUVAS homepage

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Plasma Exchange for Renal Vasculitis

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