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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

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

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

NCT ID

NCT01408836

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

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

4. Oversight

Data Monitoring Committee

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

Arm Type

Experimental

Arm Description

Plasma exchange x 7 over 14 days

Arm Title

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

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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