Please select the eligibility criteria that correspond to the clinical trial below.
Title: Treatment of ANCA-Associated Vasculitides : Corticosteroids and Pulse Cyclophosphamide Followed by Maintenance Therapy With Methotrexate or Azathioprine: a Prospective Multicenter Randomized Trial
Brief Summary: Remission of ANCA-associated vasculitis can be obtained in approximately 80% of the patients with a combination of corticosteroids and cyclophosphamide. However, relapses are frequent. This point warrants the prescription of a maintenance treatment with a less toxic immunosuppressant for several months to years. The optimal drug in this indication is not determine. We decided therefore to compare the 2 most used drugs in this indication. Induction therapy consists in the combination of corticosteroids and intravenous cyclophosphamide pulses. Corticotherapy consisted first in one daily methylprednisolone pulse, for 1 to 3 days, followed by oral prednisolone at the dose of 1 mg/kg/d for 3 weeks, then progressively tapered and stopped at the 18th month from the diagnosis. Cyclophosphamide is administered every 2 weeks for the first 3 bolus (0.6 g/m2 - D1, 15 and 30), then every 3 weeks (0.7 g/m2). Once remission is achieved, patients receive 3 additional bolus (0.7 g/m2). At that time, patients are randomized for a maintenance treatment with azathioprine (2 mg/kg/d, orally) or oral methotrexate (starting at the dose of 0.3 mg/kg/wk, then progressively increased every weeks by 2.5mg, if necessary, to a maximum and optimal dose of 25 mg/wk) for 12 months.


Options:
A: Inclusion Criteria:

* Weight of at least 88 pounds(40 kilograms)
* Diagnosis of Wegener's granulomatosis or microscopic polyangiitis according to the definitions of the Chapel Hill Consensus Conference
* Newly diagnosed patient of Wegener's granulomatosis or microscopic polyangiitis OR must be experiencing a disease flare characterized by: (a) active disease with a Birmingham Vasculitis Activity Score for Wegener's granulomatosis (BVAS/WG) of 3 or greater that would normally require treatment with CYC; OR (b) disease severe enough to require treatment with CYC; OR (c) must be positive for either PR3-ANCA (ANCA directed against proteinase 3) or MPO-ANCA (ANCA directed against myeloperoxidase)at the screening
* Willing to use acceptable forms of contraception for the duration of the study and for up to 1 year after stopping study medications
* Willing to report pregnancies (female participants or male participants' partners) occurring at any time during the study and for up to 1 year after stopping study medications
* Parent or guardian willing to provide informed consent, if applicable

Exclusion Criteria:

* Diagnosis of Churg-Strauss Syndrome according to the definitions of the Chapel Hill Consensus Conference
* Have limited disease that would not normally be treated with CYC
* Requires mechanical ventilation because of alveolar hemorrhage
* History of severe allergic reactions to human or chimeric monoclonal antibodies
* Active systemic infection
* Have a deep-space infection, such as osteomyelitis, septic arthritis, or pneumonia complicated by pleural cavity or lung abscess, within 6 months prior to study entry
* History of or current hepatitis B or C infection
* HIV (human immunodeficiency virus) infected
* Acute or chronic liver disease that, in the opinion of the investigator, may interfere with the study
* History of or active cancer diagnosed within the last 5 years. Individuals with squamous cell or basal cell carcinomas of the skin and individuals with cervical carcinoma in situ who have received curative surgical treatment may be eligible for this study.
* History of anti-glomerular basement membrane (anti-GBM) disease
* Other uncontrolled disease, including drug and alcohol abuse, that may interfere with the study
* Pregnancy or breastfeeding
B: 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.
C: 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.
D: Inclusion Criteria:

* Patients aged over 18 years-old with newly diagnosed systemic Wegener's granulomatosis,
* microscopic polyangitis with at least one factor of poor prognosis according to the five factors score (proteinuria \> 1 g/day, renal insufficiency defined as a serum creatininemia \> 140 µmol/L, specific cardiomyopathy, gastrointestinal tract and/or CNS involvement).

Exclusion Criteria:

* MPA patients with no poor prognosis factor;
* localized WG;
* relapse of previously known WG or MPA;
* treatment with corticosteroids for more than 1 month prior to diagnosis and start of immunosuppressant;
* co-existence of another multi-system autoimmune disease;
* malignancy (unless considered in complete remission and with no therapy for at least 3 years);
* contra-indication to corticosteroids or study immunosuppressants; pregnancy or no use of contraception in non-menopaused women;
* infection with human immunodeficiency virus; mental or physical disturbances not permitting to give consent.

Answer: D