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

This study has been completed.
Sponsor:
Information provided by:
Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT00430105
First received: January 31, 2007
Last updated: NA
Last verified: January 2007
History: No changes posted
  Purpose

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 Intervention Phase
ANCA Associated Systemic Vasculitis
Wegener's Granulomatosis
Microscopic Polyangiitis
Drug: cyclophosphamide
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by Cambridge University Hospitals NHS Foundation Trust:

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

Secondary Outcome Measures:
  • Adverse events
  • Vasculitis Damage Index
  • Cumulative exposure to cyclophosphamide

Estimated Enrollment: 160
Study Start Date: February 1998
Estimated Study Completion Date: April 2004
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.

  Eligibility

Ages Eligible for Study:   18 Years to 80 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00430105

Sponsors and Collaborators
Cambridge University Hospitals NHS Foundation Trust
Investigators
Study Chair: Kirsten de Groot Klinikum Offenbach GmbH, Germany
Study Chair: Caroline OS Savage University of Birmingham, UK
  More Information

No publications provided by Cambridge University Hospitals NHS Foundation Trust

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
ClinicalTrials.gov Identifier: NCT00430105     History of Changes
Other Study ID Numbers: IC20-CT97-0019, BMH4-CT97-2328, IC20-CT97-0019
Study First Received: January 31, 2007
Last Updated: January 31, 2007
Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Keywords provided by Cambridge University Hospitals NHS Foundation Trust:
Vasculitis
ANCA
Wegener's granulomatosis
Renal vasculitis
Cyclophosphamide

Additional relevant MeSH terms:
Vasculitis
Wegener Granulomatosis
Systemic Vasculitis
Microscopic Polyangiitis
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
Cyclophosphamide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists

ClinicalTrials.gov processed this record on August 27, 2014