Plasma Exchange for Renal Vasculitis (MEPEX)

This study has been terminated.
(Completed)
Sponsor:
Collaborators:
University Hospital Birmingham
Imperial College London
North West London Hospitals NHS Trust
University Hospitals, Leicester
Lund University Hospital
University Medical Centre Groningen
Fundacio Clinic
Helsinki University
Information provided by:
Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01408836
First received: August 2, 2011
Last updated: NA
Last verified: July 2011
History: No changes posted
  Purpose

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 Intervention Phase
Wegener's Granulomatosis
Microscopic Polyangiitis
Procedure: Plasma exchange
Drug: Intravenous methyl prednisolone
Drug: Methyl prednisolone
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Randomised Trial of Plasma Exchange or High Dose Methyl Prednisolone as Adjunctive Therapy for Severe Renal Vasculitis

Resource links provided by NLM:


Further study details as provided by Cambridge University Hospitals NHS Foundation Trust:

Primary Outcome Measures:
  • Renal recovery [ Time Frame: Three months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • End stage renal disease at 12 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Serum creatinine at 12 months [ Time Frame: 12 months ] [ Designated as safety issue: No ]
  • Severe adverse events [ Time Frame: 12 months ] [ Designated as safety issue: Yes ]

Enrollment: 150
Study Start Date: March 1995
Study Completion Date: December 2003
Primary Completion Date: June 2003 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01408836

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
North West London Hospitals NHS Trust
University Hospitals, Leicester
Lund University Hospital
University Medical Centre Groningen
Fundacio Clinic
Helsinki University
Investigators
Study Director: Niels Rasmussen, MD Righospitalet, Copenhagen, Denmark
  More Information

Additional Information:
No publications provided by Cambridge University Hospitals NHS Foundation Trust

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT01408836     History of Changes
Other Study ID Numbers: BMH4-CT97-2328
Study First Received: August 2, 2011
Last Updated: August 2, 2011
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Cambridge University Hospitals NHS Foundation Trust:
Vasculitis
ANCA
Therapy
Plasma exchange
Immunosuppression

Additional relevant MeSH terms:
Vasculitis
Wegener Granulomatosis
Systemic Vasculitis
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
Methylprednisolone acetate
Prednisolone acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Therapeutic Uses
Pharmacologic Actions
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on July 31, 2014