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

Sponsor:	Cambridge University Hospitals NHS Foundation Trust
Information provided by:	Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:	NCT00430105

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 II Phase III

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Safety/Efficacy Study
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:

MedlinePlus related topics: Vasculitis Wegener's Granulomatosis

Drug Information available for: Cyclophosphamide

U.S. FDA Resources

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:

A new diagnosis of WG, MP or renal-limited vasculitis (RLV) (appendix 5). Patients not previously treated with cytotoxic drugs will be permitted.
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.
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).
Age 18-80 years.

Exclusion Criteria:

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.
Co-existence of another multisystem autoimmune disease, e.g. SLE.
Hepatitis Be antigen positive or Hepatitis C antibody positive.
Known HIV positivity (HIV testing will not be a requirement for this trial).
Serum creatinine > 500umol/l (consider MEPEX trial).
Immediately life-threatening organ manifestations (e.g. lung haemorrhage or dialysis dependence).
Previous malignancy (usually exclude unless agreed with trial co-ordinator).
Pregnancy or inadequate contraception if female.
Anti-GBM antibody positivity.

Contacts and Locations

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 National Clinical Trials Identifier (NCT ID):

de Groot K, Harper L, Jayne DR, Flores Suarez LF, Gregorini G, Gross WL, Luqmani R, Pusey CD, Rasmussen N, Sinico RA, Tesar V, Vanhille P, Westman K, Savage CO; EUVAS (European Vasculitis Study Group). Pulse versus daily oral cyclophosphamide for induction of remission in antineutrophil cytoplasmic antibody-associated vasculitis: a randomized trial. Ann Intern Med. 2009 May 19;150(10):670-80.

Study ID Numbers:	IC20-CT97-0019, BMH4-CT97-2328, IC20-CT97-0019
Study First Received:	January 31, 2007
Last Updated:	January 31, 2007
ClinicalTrials.gov Identifier:	NCT00430105 History of Changes
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:

Lung Diseases, Interstitial
Vasculitis
Molecular Mechanisms of Pharmacological Action
Immunologic Factors
Antineoplastic Agents
Physiological Effects of Drugs
Vascular Diseases
Cyclophosphamide
Immunosuppressive Agents
Pharmacologic Actions
Wegener Granulomatosis

Respiratory Tract Diseases
Urologic Diseases
Therapeutic Uses
Lung Diseases
Myeloablative Agonists
Cardiovascular Diseases
Antineoplastic Agents, Alkylating
Kidney Diseases
Antirheumatic Agents
Alkylating Agents

ClinicalTrials.gov processed this record on February 08, 2010