Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomised Trial of Plasma Exchange or High Dose Methyl Prednisolone as Adjunctive Therapy for Severe Renal Vasculitis
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.


Options:
A: Inclusion Criteria:

Inclusion (requires all):

* New diagnosis of AASV (WG or MPA) (within the previous six months)
* Active disease (defined by at least one major or three minor BVAS 2003 items, see appendix 1)
* ANCA positivity (c-ANCA and PR3-ANCA or p-ANCA and MPO-ANCA) or histology confirming active vasculitis from any organ (see appendix )
* Written informed consent

Exclusion Criteria:

* Previous treatment with:

  * MMF: more than two weeks ever.
  * Cyclophosphamide: more than two weeks daily oral or more than 1 pulse of IV CYC (15mg/kg)
  * Rituximab or high dose intravenous immunoglobulin within the last twelve months
* Active infection (including hepatitis B, C, HIV and tuberculosis).
* Known hypersensitivity to MMF, AZA or CYC.
* Cancer or an individual history of cancer (other than resected basal cell skin carcinoma).
* Females who are pregnant, breast feeding, or at risk of pregnancy and not using a medically acceptable form of contraception.
* Any condition judged by the investigator that would cause the study to be detrimental to the patient.
* Any other multi-system autoimmune disease including Churg Strauss angiitis, SLE, anti GBM disease and cryoglobulinaemia.
B: Inclusion Criteria:

* Wegener's granulomatosis Or microscopic polyangiitis complying Or kidney-limited disease With or without detectable ANCA (anti-neutrophil cytoplasmic antibodies) at the time of diagnosis or relapse, and at remission.
* Who have achieved remission using a treatment combining corticosteroids and an immunosuppressive agent according to current French guideline, including corticosteroids, cyclophosphamide IV or oral (the use of another immunosuppressant is allowed, according to the current French guidelines, as well as plasma exchanges and/or IV immunoglobulins).
* Interval of 1 month between the end of the immunosuppressant treatment and the randomization time
* Age \> 18 years and \< 75 years when the diagnosis is confirmed.
* Informed and having signed the consent form to take part in the study.

Exclusion Criteria:

* Other systemic vasculitis
* Secondary vasculitis (following neoplastic disease or an infection in particular)·
* Induction treatment with a regimen not corresponding to that recommended in France.
* Patient who has not achieved remission.·
* Patient who has already received a treatment by biological agents (monoclonal antibody - antiCD20 or antiTNFα).
* Incapacity or refusal to understand or sign the informed consent form.
* Incapacity or refusal to adhere to treatment or perform the follow-up examinations required by the study. Non-compliance·
* Allergy, documented hypersensitivity or contraindication to the study medication (cyclophosphamide, corticosteroids, azathioprine, rituximab),
* History of severe allergic or anaphylactic reactions to humanized or murine monoclonal antibodies.
* Patients receiving allopurinol cannot be included if the allopurinol must absolutely be maintained.
* Pregnancy, breastfeeding. Women of childbearing age must use a reliable method of contraception throughout the duration of immunosuppressive treatment up to 1 year after the last infusion of rituximab
* Infection by HIV, HCV or HBV
* Progressive, uncontrolled infection requiring a prolonged treatment (tuberculosis, HIV infection, etc.).
* Severe infection declared during the 3 months before randomization (CMV, HBV, HHV8, HCV, HIV, tuberculosis).
* Progressive cancer or malignant blood disease diagnosed during the 5 years before the diagnosis of vasculitis. Patients suffering from non-metastatic prostate cancer or those cured of a cancer or a malignant blood disorder for more than 5 years and not taking any antineoplastic agents for more than 5 years may be included.
* patients presenting a systemic disease receiving protocolized treatments (azathioprine, rituximab) which could have unexpected and inappropriate side effects.
* Participation in another clinical research protocol during the 4 weeks before inclusion.
* Any medical or psychiatric disorder which, in the investigator's opinion, may prevent the administration of treatment and patient follow-up according to the protocol, and/or which may expose the patient to a too greater risk of an adverse effect.
* No social security
* Churg and Strauss syndrome
* viral, bacterial or fungic or mycobacterial infection uncontrolled in the 4 weeks before the inclusion
* history of deep tissue infection (fasciitis, osteomyelitis, septic arthritis)in the first year before the inclusion
* History of chronic and severe or recurrent infection or history of preexisting disease predisposing to severe infection
* Severe immunodepression
* Administration of live vaccine in the four weeks before inclusion
* severe chronic obstructive pulmonary diseases (VEMS \< 50 % or dyspnea grade III)
* chronic heart failure stade III and IV (NYHA)
* History of recent acute coronary syndrome
C: Inclusion Criteria:

1. A new diagnosis of WG, MP or renal-limited vasculitis (RLV) (appendix 5). Patients not previously treated with cytotoxic drugs will be permitted.
2. Renal involvement attributable to active WG, MP or RLV with at least one of the following:

   * elevated serum creatinine between 150 and 500 umol/l.
   * biopsy demonstrating necrotizing glomerulonephritis.
   * red cell casts.
   * haematuria with \>30 red blood cells/high powered field and proteinuria \> 1g/24hr.
3. ANCA positivity or confirmatory histology or both (appendix 5). ANCA positivity requires a typical CANCA pattern by indirect immunofluorescence (IIF), (preferably confirmed by anti-PR3 ELISA), or the presence of PR3-ANCA or MPO-ANCA determined by ELISA, PANCA requires confirmation by anti-MPO ELISA \[6\]. (Central review of ANCA serology and histology will be performed).
4. Age 18-80 years.

Exclusion Criteria:

1. More than two weeks treatment with cyclophosphamide (CYC) or other cytotoxic drug within previous year or with oral corticosteroids (OCS) for more than 4 weeks. If the patient has received \>1.0g of methyl-prednisolone prior to the study start, discuss with trial co-ordinator.
2. Co-existence of another multisystem autoimmune disease, e.g. SLE.
3. Hepatitis Be antigen positive or Hepatitis C antibody positive.
4. Known HIV positivity (HIV testing will not be a requirement for this trial).
5. Serum creatinine \> 500umol/l (consider MEPEX trial).
6. Immediately life-threatening organ manifestations (e.g. lung haemorrhage or dialysis dependence).
7. Previous malignancy (usually exclude unless agreed with trial co-ordinator).
8. Pregnancy or inadequate contraception if female.
9. Anti-GBM antibody positivity.
D: 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.

Answer: D