Clinical Trial of Mycophenolate Versus Cyclophosphamide in ANCA Vasculitis
Information source: Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Vasculitis
Intervention: mycophenolate mofetil (Drug); cyclophosphamide (Drug)
Phase: Phase 2/Phase 3
Status: Completed
Sponsored by: Cambridge University Hospitals NHS Foundation Trust Official(s) and/or principal investigator(s): David Jayne, Principal Investigator, Affiliation: Addenbrooke's Hospital, Cambridge, UK Lorraine Harper, Principal Investigator, Affiliation: Birmingham University, UK Rachel Jones, Principal Investigator, Affiliation: Addenbrooke's Hospital, UK
Summary
The purpose of this study is to investigate whether mycophenolate mofetil is effective as
treatment for new cases of ANCA associated vasculitis.
Clinical Details
Official title: A Randomised Clinical Trial of Mycophenolate Mofetil Versus Cyclophosphamide for Remission Induction in ANCA Associated Vasculitis.
Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: Remission rates at 6 months
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).
Eligibility
Minimum age: N/A.
Maximum age: N/A.
Gender(s): Both.
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.
Locations and Contacts
Addenbrookes Hospital, Cambridge, Cambridgeshire CB22QQ, United Kingdom
Additional Information
EUVAS web site
Starting date: March 2007
Last updated: December 5, 2013
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