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

January 31, 2007 updated by: Cambridge University Hospitals NHS Foundation Trust

Randomized Trial of Intravenous Pulse Versus Oral Continuous Cyclophosphamide for Induction of Remission in Systemic ANCA-Associated Vasculitides

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment

160

Phase

  • Phase 2
  • Phase 3

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 80 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Disease free period, time from remission to relapse or study end.

Secondary Outcome Measures

Outcome Measure
Adverse events
Vasculitis Damage Index
Cumulative exposure to cyclophosphamide

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cambridge University Hospitals NHS Foundation Trust

Investigators

  • Study Chair: Kirsten de Groot, Klinikum Offenbach GmbH, Germany
  • Study Chair: Caroline OS Savage, University of Birmingham

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 1998

Study Completion

April 1, 2004

Study Registration Dates

First Submitted

January 31, 2007

First Submitted That Met QC Criteria

January 31, 2007

First Posted (Estimate)

February 1, 2007

Study Record Updates

Last Update Posted (Estimate)

February 1, 2007

Last Update Submitted That Met QC Criteria

January 31, 2007

Last Verified

January 1, 2007

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • IC20-CT97-0019
  • BMH4-CT97-2328

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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