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Pulse Versus Continuous Cyclophosphamide for Induction of Remission in ANCA-Associated Vasculitides

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00430105
Recruitment Status : Completed
First Posted : February 1, 2007
Last Update Posted : February 1, 2007
Information provided by:
Cambridge University Hospitals NHS Foundation Trust

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.

Condition or disease Intervention/treatment Phase
ANCA Associated Systemic Vasculitis Wegener's Granulomatosis Microscopic Polyangiitis Drug: cyclophosphamide Phase 2 Phase 3

Detailed Description:

The primary, ANCA-associated systemic vasculitides (AASV), including Wegener's granulomatosis and microscopic polyangiitis, are progressive, multisystem, autoimmune diseases which respond to immunosuppressive therapy. Their treatment with corticosteroids and cytotoxic drugs has been standardised in a first wave of studies (ECSYSVASTRIAL project), but limitations of such regimens include only partial efficacy and appreciable treatment-related toxicity.

The present trial, CYCLOPS, aims to reduce the cumulative exposure to immunosuppressive drugs by administering cyclophosphamide (CYC) as intermittent pulses. The potential benefit of using CYC in this way for AASV has been demonstrated in preliminary, smaller studies. Patients with previously untreated AASV and, "generalised", but not life threatening, disease with renal involvement, will be randomised to either continuous oral CYC or intermittent pulse CYC. CYC will be continued until three months after remission has been achieved, with a minimum CYC total duration of six months and maximum duration of twelve months; both limbs will then receive the same maintenance regimen of azathioprine and prednisolone.

The study will last 18 months. The primary end-point is the disease-free period, taken as the period of time from remission until relapse or study end; secondary end-points are adverse effects, cumulative damage and immunosuppressive drug exposure. 160 patients will be required.

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Study Type : Interventional  (Clinical Trial)
Enrollment : 160 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Randomized Trial of Intravenous Pulse Versus Oral Continuous Cyclophosphamide for Induction of Remission in Systemic ANCA-Associated Vasculitides
Study Start Date : February 1998
Study Completion Date : April 2004

Primary Outcome Measures :
  1. Disease free period, time from remission to relapse or study end.

Secondary Outcome Measures :
  1. Adverse events
  2. Vasculitis Damage Index
  3. Cumulative exposure to cyclophosphamide

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00430105

Sponsors and Collaborators
Cambridge University Hospitals NHS Foundation Trust
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Study Chair: Kirsten de Groot Klinikum Offenbach GmbH, Germany
Study Chair: Caroline OS Savage University of Birmingham
Publications automatically indexed to this study by Identifier (NCT Number):
Layout table for additonal information Identifier: NCT00430105    
Other Study ID Numbers: IC20-CT97-0019
First Posted: February 1, 2007    Key Record Dates
Last Update Posted: February 1, 2007
Last Verified: January 2007
Keywords provided by Cambridge University Hospitals NHS Foundation Trust:
Wegener's granulomatosis
Renal vasculitis
Additional relevant MeSH terms:
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Granulomatosis with Polyangiitis
Microscopic Polyangiitis
Systemic Vasculitis
Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Vascular Diseases
Cardiovascular Diseases
Lung Diseases, Interstitial
Lung Diseases
Respiratory Tract Diseases
Autoimmune Diseases
Immune System Diseases
Cerebral Small Vessel Diseases
Cerebrovascular Disorders
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists