Please select the eligibility criteria that correspond to the clinical trial below.
Title: Randomized Trial of Intravenous Pulse Versus Oral Continuous Cyclophosphamide for Induction of Remission in Systemic ANCA-Associated Vasculitides
Brief Summary: A comparison of intermittent pulsed cyclophosphamide to daily oral cyclophosphamide for the treatment of ANCA-associated systemic vasculitides with kidney involvement.

Performed by the European Vasculitis Study group.


Options:
A: 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.
B: 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.
C: Inclusion Criteria:

* Wegener's granulomatosis, Microscopic polyangiitis and Churg-Strauss syndrome (satisfying ACR or chapel Hill classification) relapsing either under corticosteroid and immunosuppressant therapies or after one year post treatment
* Age \> 18 years old
* Written informed consent

Exclusion Criteria:

* Systemic vasculitides not previously treated with corticosteroid and immunosuppressant(s)
* Systemic vasculitides treated with corticosteroids and immunosuppressant therapies, but with treatment cessation more than 12 months ago
* Polyarteritis nodosa
* Absence of poor prognosis criteria (according to FFS)
* Nephritis ± renal impairment
* Cancer or malignancy
* Psychiatric disease, lack of compliance
* Age under 18 years old
* Lack of written informed consent
* Other vasculitides (post viral infection and skin localisation)
D: Inclusion Criteria:

* Men and women with newly diagnosed Churg-Strauss syndrome;
* absence of poor prognostic factors as defined by the five-factor score (serum creatinine \> 140 μmol/l or 1.58 mg/dl, proteinuria \> 1 g/day, severe gastrointestinal tract involvement, specific cardiomyopathy and/or central nervous system involvement;
* written informed consent.

Exclusion Criteria:

* age \< 15 years, previously treated Churg-Strauss syndrome;
* history of cancer;
* pregnant or breast-feeding women;
* psychiatric disorders that might compromise compliance with therapy;
* contraindication to study drug;
* other ongoing therapeutic trial;
* concomitant viral hepatitis B or C or human immunodeficiency virus (HIV) infection

Answer: A