Clinical Trial of Mycophenolate Versus Cyclophosphamide in ANCA Vasculitis

NCT ID: NCT00414128

Last Updated: 2013-12-06

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 140 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-03-31
• Study Completion Date: 2013-02-28

Brief Summary

The purpose of this study is to investigate whether mycophenolate mofetil is effective as treatment for new cases of ANCA associated vasculitis.

Detailed Description

There is a clear need for improved therapy in ANCA associated vasculitis where current treatments are toxic and contribute to poor outcomes. Conventional therapy combines cyclophosphamide with prednisolone but is associated with severe adverse events in 35%, early mortality, malignancy and infertility. Mycophenolate mofetil (MMF) is a newer immunosuppressive drug which has superior efficacy to azathioprine in solid organ transplantation. MMF is an effective alternative to cyclophosphamide in lupus nephritis. Open label studies and retrospective surveys point to the efficacy and low toxicity of MMF in vasculitis.

We hypothesise that MMF not be less effective than cyclophosphamide for remission induction in AASV. 140 new patients will be randomised to MMF 3g/day or a European consensus intravenous cyclophosphamide regimen, with the same prednisolone dosing. Following a six month induction course all patients will receive consensus remission maintenance treatment with azathioprine and prednisolone. The primary end-point will be remission rate by six months, secondary end-points include relapse rate at 18 months and safety. The trial will be conducted in 10 countries by members of the European Vasculitis Study Group (EUVAS). The trial duration will be 42 months (24 months recruitment, 18 months follow up).

Conditions

Vasculitis

Keywords

vasculitis; ANCA; mycophenolate mofetil; cyclophosphamide; Anti neutrophil cytoplasm antibody associated vasculitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

mycophenolate mofetil

Mycophenolate mofetil for 3-6 months until in stable remission, dose 2-3g/day

Group Type: EXPERIMENTAL

mycophenolate mofetil

Intervention Type: DRUG

2-3g/day for 3-6 months, in tablet, capsule or liquid form

cyclophosphamide

pulsed intravenous cyclophosphamide 15mg/kg for 3-6 months (6-10 doses)until in stable remission

Group Type: ACTIVE_COMPARATOR

cyclophosphamide

Intervention Type: DRUG

intravenous cyclophosphamide, 15mg/kg with dose reductions according to age and renal function, for 3-6 months (6-10 doses total)

Interventions

mycophenolate mofetil

2-3g/day for 3-6 months, in tablet, capsule or liquid form

Intervention Type: DRUG

cyclophosphamide

intravenous cyclophosphamide, 15mg/kg with dose reductions according to age and renal function, for 3-6 months (6-10 doses total)

Intervention Type: DRUG

Other Intervention Names

Cellcept; cytoxan

Eligibility Criteria

Inclusion Criteria

Inclusion (requires all):

• New diagnosis of AASV (WG or MPA) (within the previous six months)
• Active disease (defined by at least one major or three minor BVAS 2003 items, see appendix 1)
• ANCA positivity (c-ANCA and PR3-ANCA or p-ANCA and MPO-ANCA) or histology confirming active vasculitis from any organ (see appendix )
• Written informed consent

Exclusion Criteria

• Previous treatment with:

• MMF: more than two weeks ever.
• Cyclophosphamide: more than two weeks daily oral or more than 1 pulse of IV CYC (15mg/kg)
• Rituximab or high dose intravenous immunoglobulin within the last twelve months
• Active infection (including hepatitis B, C, HIV and tuberculosis).
• Known hypersensitivity to MMF, AZA or CYC.
• Cancer or an individual history of cancer (other than resected basal cell skin carcinoma).
• Females who are pregnant, breast feeding, or at risk of pregnancy and not using a medically acceptable form of contraception.
• Any condition judged by the investigator that would cause the study to be detrimental to the patient.
• Any other multi-system autoimmune disease including Churg Strauss angiitis, SLE, anti GBM disease and cryoglobulinaemia.

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Aspreva Pharmaceuticals

INDUSTRY

Sponsor Role: collaborator

Vifor Pharma

INDUSTRY

Sponsor Role: collaborator

Cambridge University Hospitals NHS Foundation Trust

OTHER

Sponsor Role: lead

Responsible Party

David Jayne

Drs David Jayne Consultant in Nephrology and Vasculitis

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

David Jayne

Role: PRINCIPAL_INVESTIGATOR

Addenbrooke's Hospital, Cambridge, UK

Lorraine Harper

Role: PRINCIPAL_INVESTIGATOR

Birmingham University, UK

Rachel Jones

Role: PRINCIPAL_INVESTIGATOR

Addenbrooke's Hospital, UK

Locations

Addenbrookes Hospital

Cambridge, Cambridgeshire, United Kingdom

Countries

United Kingdom

References

Jones RB, Hiemstra TF, Ballarin J, Blockmans DE, Brogan P, Bruchfeld A, Cid MC, Dahlsveen K, de Zoysa J, Espigol-Frigole G, Lanyon P, Peh CA, Tesar V, Vaglio A, Walsh M, Walsh D, Walters G, Harper L, Jayne D; European Vasculitis Study Group (EUVAS). Mycophenolate mofetil versus cyclophosphamide for remission induction in ANCA-associated vasculitis: a randomised, non-inferiority trial. Ann Rheum Dis. 2019 Mar;78(3):399-405. doi: 10.1136/annrheumdis-2018-214245. Epub 2019 Jan 5.

Reference Type: DERIVED

PMID: 30612116 (View on PubMed)

Related Links

http://vasculitis.org

EUVAS web site

Other Identifiers

Eudract: 2006-001663-33

Identifier Type: -

Identifier Source: secondary_id

MYCYC

Identifier Type: -

Identifier Source: org_study_id