Clinical trial NCT01408836: Plasma Exchange for Renal Vasculitis
Official title: Randomised Trial of Plasma Exchange or High Dose Methyl Prednisolone as Adjunctive Therapy for Severe Renal Vasculitis
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE2
PHASE3
Conditions: Wegener's Granulomatosis
Microscopic Polyangiitis
Keywords: Vasculitis
ANCA
Therapy
Plasma exchange
Immunosuppression
Lead sponsor: Cambridge University Hospitals NHS Foundation Trust
Sponsor class: OTHER
Collaborators: name: University Hospital Birmingham
name: Imperial College London
name: London North West Healthcare NHS Trust
name: University Hospitals, Leicester
name: Lund University Hospital
name: University Medical Center Groningen
name: Fundacio Clinic Barcelona
name: University of Helsinki
First posted: 2011-08-03
Enrollment: 150
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Renal recovery
timeFrame: Three months
Secondary outcomes:
measure: End stage renal disease at 12 months
timeFrame: 12 months
measure: Serum creatinine at 12 months
timeFrame: 12 months
measure: Severe adverse events
timeFrame: 12 months
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Addenbrooke's Hospital
Study officials:
affiliation: Righospitalet, Copenhagen, Denmark
name: Niels Rasmussen, MD
role: STUDY_DIRECTOR
References:
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.