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:

* Newly diagnosed patients with WG, MPA or renal-limited vasculitis.
* ANCA positivity. ANCA positivity requires PR3-ANCA or a typical cANCA pattern by indirect immunofluorescence (IIF), preferably confirmed by anti-PR3 ELISA. MPO-ANCA determined by ELISA requires demonstration of pANCA, and pANCA by IIF requires confirmation by anti-MPO ELISA. Optionally, central review of ANCA serology can be performed.
* Age 18 to 75 years

Exclusion Criteria:

* Any cytotoxic drug within previous year, unless started within one months of entry and according to the protocol design
* Co-existence of another systemic autoimmune disease, e.g. SLE
* Hepatitis B or Hepatitis C infection
* HIV positivity
* Failure to achieve remission after 6 months of CYC therapy
* Failure to control progressive disease with induction protocol
* Malignancy (usually exclude unless agreed with trial co-ordinator)
* Pregnancy or inadequate contraception
* Age below 18 and above 75 years\*
* Endstage renal failure unless active extrarenal disease requires treatment (temporal dependency of hemodialysis is not an exclusion criterion)
* Inability for informed consent

  * After discussion with the trial administrator, patients less than 18 years may be incorporated on separate application according to the appropriate local ethic committee.
B: Key Inclusion Criteria:

* Clinical diagnosis Wegener's granulomatosis or microscopic polyangiitis by Chapel Hill criteria.
* Disease flare in the past 26 weeks requiring treatment with high dose corticosteroids and 1 of the following medications: rituximab, oral cyclophosphamide OR IV cyclophosphamide.
* Tested positive for anti-proteinase 3 (anti-PR3) or anti-myeloperoxidase (anti-MPO) antibodies at any time prior to enrollment.
* Achieve remission no more than 26 weeks after first dose of induction treatment. Remission is defined as a Birmingham Vasculitis Activity (BVAS) score of 0 and receiving less than 10 mg/day of oral prednisone (or equivalent) on 2 consecutive visits 21 to 35 days apart.
* Maintenance therapy on this study must start no more than 2 weeks after confirmation of remission.

Key Exclusion Criteria:

* Pregnant or nursing.
* Receipt of a B cell targeted therapy (other than rituximab) at anytime
* Receipt of an investigational biological agent within the past 60 days.
* Required management of acute or chronic infections within the past 60 days.
* Current drug or alcohol abuse or dependence.
* Current or past positive test for human immunodeficiency virus (HIV), hepatitis B, or hepatitis C.
* History of severe allergic reaction to contrast agents or biological medicines.
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:

* Newly diagnosed WG, MPA, PAN without HBV infection, or CSS
* Patients can be still be enrolled within 1 month after starting corticosteroids if prescribed according to protocol.
* within or after the 65th of anniversary
* Age ≥ 65 years

Exclusion Criteria:

* Any cytotoxic drug within previous year
* Co-existence of another systemic autoimmune disease, e.g., SLE, RA
* Virus-associated vasculitides
* HIV positivity
* Malignancy (usually excluded unless approved by the trial coordinator)
* Age \< 65 years
* Inability to give informed consent

Answer: C