A randomised clinical trial of mycophenolate mofetil versus cyclophosphamide for remission induction in ANCA associated vasculitis

ISRCTN	ISRCTN15366107
DOI	https://doi.org/10.1186/ISRCTN15366107
EudraCT/CTIS number	2006-001663-33
ClinicalTrials.gov number	NCT00414128
Secondary identifying numbers	4509

Submission date: 28/05/2010
Registration date: 28/05/2010
Last edited: 09/09/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

Not provided at time of registration

Contact information

Mrs Karen Dahlsveen
Scientific

Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
United Kingdom

Phone	+44 1223 336819
Email	mycycmed@hermes.cam.ac.uk

Study information

Study design	Multicentre randomised interventional treatment trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Scientific title	A randomised clinical trial of mycophenolate mofetil versus cyclophosphamide for remission induction in ANCA associated vasculitis
Study acronym	MYCYC
Study hypothesis	There is a clear need for improved therapy in antineutrophil cytoplasmic antibody (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.
Ethics approval(s)	20/05/2008, ref: 07/H0606/136
Condition	Topic: Medicines for Children Research Network; Subtopic: All Diagnoses; Disease: All Diseases
Intervention	140 new patients will be randomised to MMF 2g/day or a European consensus intravenous cyclophosphamide regimen, with the same prednisolone dosing. Following a 6-month induction course all patients will receive consensus remission maintenance treatment with azathioprine and prednisolone.
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Phase III
Drug / device / biological / vaccine name(s)	Mycophenolate mofetil, cyclophosphamide, azathioprine, prednisolone
Primary outcome measure	Remission rate by 6 months
Secondary outcome measures	1. Relapse rate at 18 months 2. Safety
Overall study start date	12/03/2007
Overall study end date	01/01/2010

Eligibility

Participant type(s)	Patient
Age group	Other
Sex	Both
Target number of participants	Planned sample size: 140; UK sample size: 20
Total final enrolment	140
Participant inclusion criteria	1. New diagnosis of ANCA-associated systemic vasculitis (AASV) (Wegener's granulomatosis [WG] or microscopic polyangiitis [MPA]) (within the previous six months) 2. Active disease (defined by at least one major or three minor BVAS 2003 items) 3. ANCA positivity (c-ANCA and PR3-ANCA or p-ANCA and MPO-ANCA) or histology confirming active vasculitis from any organ 4. Written informed consent 5. Aged 5 years or older, either sex
Participant exclusion criteria	1. Previous treatment with: 1.1. MMF: more than two weeks ever 1.2. Cyclophosphamide: more than two weeks daily oral or more than 1 pulse of intravenous (IV) CYC (15 mg/kg) 1.3. Rituximab or high dose intravenous immunoglobulin within the last twelve months 2. Active infection (including hepatitis B, C, human immunodeficiency virus [HIV] and tuberculosis) 3. Known hypersensitivity to MMF, azathioprine (AZA) or CYC 4. Cancer or an individual history of cancer (other than resected basal cell skin carcinoma) 5. Females who are pregnant, breast feeding, or at risk of pregnancy and not using a medically acceptable form of contraception 6. Any condition judged by the investigator that would cause the study to be detrimental to the patient 7. Any other multi-system autoimmune disease including Churg Strauss angiitis, systemic lupus erythematosus (SLE), anti-glomerular basement membrane (anti-GBM) disease and cryoglobulinaemia 8. Active serious digestive system disease (e.g., inflammatory bowel disease) 9. Patients with imminently life threatening vasculitis (diffuse alveolar haemorrhage, intestinal perforation or major haemorrhage, cerebral vasculitis and cardiac vasculitis) 10. Patients with rapidly progressive glomerulonephritis and declining renal function. Defined as estimated glomerular filtration rate (GFR) fall greater than 20% in previous two weeks. 11. GFR less than 15 ml/min at entry or on dialysis
Recruitment start date	12/03/2007
Recruitment end date	01/01/2010

Locations

Countries of recruitment

England
United Kingdom

Study participating centre

Addenbrookes Hospital

Cambridge
CB2 0QQ
United Kingdom

Sponsor information

Cambridge University Hospitals NHS Foundation Trust
Hospital/treatment centre

Addenbrookes Hospital
Hills Road
Cambridge
CB2 0QQ
England
United Kingdom

Website	http://www.cuh.org.uk/addenbrookes/addenbrookes_index.html
"ROR"	https://ror.org/04v54gj93

Funders

Funder type

Industry

Aspreva (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Basic results			16/05/2019	No	No
Results article	results	01/03/2019	09/09/2019	Yes	No

Editorial Notes

09/09/2019: ClinicalTrials.gov number and publication reference added.
16/05/2019: The following changes were made to the trial record:
1. Added clinicaltrialsregister.eu link to basic results (scientific).
2. The total final enrolment was added.
15/03/2017: No publications found in PubMed, verifying study status with principal investigator