Contact information
Type
Scientific
Primary contact
Prof Kerstin Westman
ORCID ID
Contact details
Dept. of Nephrology and Transplantation
University Hospital MAS (UMAS)
Malmo
205 02
Sweden
kerstin.westman@skane.se
Additional identifiers
EudraCT number
ClinicalTrials.gov number
Protocol/serial number
N/A
Study information
Scientific title
Long-term follow up of patients who participated in previous Vasculitis trials
Acronym
Study hypothesis
Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV), Wegeners granulomatosis (WG) and microscopic polyangiitis (MPA) are primary vasculitides of unknown cause characterised by necrotising inflammation involving predominantly small blood vessels and the presence of circulating anti-neutrophil cytoplasm antibodies (ANCA) in the majority of patients at diagnosis. They are often grouped as ANCA-AAV because of striking similarities in histology, absence of immune deposits, response to therapy and the likely contribution of ANCA to the pathogenesis.
The primary aim of this study is to determine the long-term survival of patients with ANCA-AAV, , who participated in randomised controlled trials conducted by the European Vasculitis Study Group (EUVAS) compared to the general population with a median follow-up greater than five years.
Secondary aims are to investigate the survival with independent renal function and renal function at five years follow up in addition to the frequency of other severe organ failure such as blindness and oxygen dependency. The survival without disease relapse and the severity and organ involvement of disease relapses will be studied.
Important adverse events such as the frequency and nature of malignant disease, cardiovascular disease, serious infections and skeletal fractures will be investigated. The causes of death will be noted.
Prognostic factors at entry and at 1 year on long-term survival and renal outcome will be identified including the predictive value of renal histology at presentation.
The performance of currently used disease assessment tools like the Birmingham Vasculitis Activity Score (BVAS) for disease activity, the Vasculitis Damage Index (VDI) for damage and the Short-form 36 (SF-36) for quality of life will be assessed. This study will help define the natural history of AAV, will serve as a reference base for new clinical trials and identify the major long-term goals and challenges for the management of AAV.
Publications from original trials:
1. de Groot K, Harper L, Jayne DR, Flores Suarez LF, Gregorini G, Gross WL, et al. 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.
2. De Groot K, Rasmussen N, Bacon PA, Tervaert JW, Feighery C, Gregorini G, et al. Randomized trial of cyclophosphamide versus methotrexate for induction of remission in early systemic antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2005 Aug;52(8):2461-9.
3. Jayne D, Rasmussen N, Andrassy K, Bacon P, Tervaert JW, Dadoniene J, et al. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med. 2003 Jul 3;349(1):36-44.
4. Jayne DR, Gaskin G, Rasmussen N, Abramowicz D, Ferrario F, Guillevin L, et al. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J AmSocNephrol. 2007 2007/07//;18(7):2180-8.
Ethics approval
West Midlands Multi-centre Research Ethics Committee approved ammendment 1 on 22/09/2004 (ref: MREC/98/7/37)
Study design
Observational long-term follow up of patients who participated in four multi-centre randomised controlled trials after median follow- up of five years
Primary study design
Observational
Secondary study design
Randomised controlled trial
Trial setting
Hospitals
Trial type
Treatment
Patient information sheet
Not available in web format, please use contact details below to request a patient information sheet
Condition
Anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis (AAV); Wegeners granulomatosis (WG); microscopic polyangiitis (MPA)
Intervention
A questionnaire will be send to all participating investigators and data collected on the occurrence and time to event of the following outcomes:
1. Survival
2. Renal survival (including incidence and latency to start of renal replacement and time to transplant)
3. Renal function at 5 years as assessed by 4 factor Modification of Diet in Renal Disease (MDRD) formula
4. Organ failure (such as blindness, pulmonary disease requiring long-term oxygen therapy etc)
5. Immunosuppressive therapy including cumulative cyclophosphamide exposure
6. Incidence and nature of malignancies including non-melanoma skin cancers and myelodysplasia
7. Relapse and renal relapse
8. Cardiovascular events (CVA, MI, PVD, thrombo-embolic events)
9. Diabetes mellitus
10. Infections requiring hospitalisation
11. Skeletal fractures
12. Cause of death
13. Vasculitis Damage Index at 5 years
Intervention type
Other
Phase
Not Specified
Drug names
Primary outcome measure
Long-term survival of patients with ANCA associated vasculitis compared to age, sex, year and country matched background population (Kaplan Meier analysis, comparison to background population according to Hakkulinen method)
Secondary outcome measures
1. Prognostic factors at presentation-multi-variable analysis
2. Cumulative damage according to Vasculitis Damage Index at 1 and 5 years
3. Relapse rate and relapse free survival by Kaplan Meier method
4. Renal function as survival with independent renal function by Kaplan Meier method and estimated glomerular filtration rate
(eGFR) at 5 year follow up.
5. Incidence and time point of severe organ failure (eg blindness, oxygen dependency)
6. Cumulative incidence of malignancies including non-melanoma skin cancer and myelodysplasia
7. Cardiovascular morbidity and mortality
Overall trial start date
01/09/2004
Overall trial end date
31/01/2007
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Patients with newly diagnosed Anti-Neutrophil Cytoplasm Antibody Vasculitis recruited into one of four randomised controlled trials, NORAM, CYCAZAREM, MEPEX, CYCLOPS performed by European Vasculitis Study Group
2. The patients were recruited during the period of 1995 to 2002
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
535
Participant exclusion criteria
1. Patients withdrawn from original study due to incorrect diagnosis
2. Consent withheld by patient
Recruitment start date
01/09/2004
Recruitment end date
31/01/2007
Locations
Countries of recruitment
Belgium, Czech Republic, Denmark, Finland, France, Germany, Ireland, Italy, Mexico, Netherlands, Spain, Sweden, Switzerland, United Kingdom
Trial participating centre
Dept. of Nephrology and Transplantation
Malmo
205 02
Sweden
Sponsor information
Organisation
University of Birmingham/University Hospital NHS Foundation Trust (UK)
Sponsor details
University of Birmingham
Edgbaston
Birmingham
BT15 2TT
United Kingdom
+44 (0)121 414 3344
mdsenquiries@contacts.bham.ac.uk
Sponsor type
University/education
Website
Funders
Funder type
Research council
Funder name
European League Against Rheumatism (EULAR) (Europe)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Participant level data
Not provided at time of registration
Basic results (scientific)
Publication list
1. 2011 results in: http://www.ncbi.nlm.nih.gov/pubmed/21109517
2. 2011 results in: http://www.ncbi.nlm.nih.gov/pubmed/21452269
3. 2011 results in: http://www.ncbi.nlm.nih.gov/pubmed/21616914
4. 2013 results in: http://www.ncbi.nlm.nih.gov/pubmed/23615499
Publication citations
-
Results
Flossmann O, Berden A, de Groot K, Hagen C, Harper L, Heijl C, Höglund P, Jayne D, Luqmani R, Mahr A, Mukhtyar C, Pusey C, Rasmussen N, Stegeman C, Walsh M, Westman K, , Long-term patient survival in ANCA-associated vasculitis., Ann. Rheum. Dis., 2011, 70, 3, 488-494, doi: 10.1136/ard.2010.137778.
-
Results
Suppiah R, Judge A, Batra R, Flossmann O, Harper L, Höglund P, Javaid MK, Jayne D, Mukhtyar C, Westman K, Davis JC, Hoffman GS, McCune WJ, Merkel PA, St Clair EW, Seo P, Spiera R, Stone JH, Luqmani R, A model to predict cardiovascular events in patients with newly diagnosed Wegener's granulomatosis and microscopic polyangiitis., Arthritis Care Res (Hoboken), 2011, 63, 4, 588-596, doi: 10.1002/acr.20433.
-
Results
Heijl C, Harper L, Flossmann O, Stücker I, Scott DG, Watts RA, Höglund P, Westman K, Mahr A, , Incidence of malignancy in patients treated for antineutrophil cytoplasm antibody-associated vasculitis: follow-up data from European Vasculitis Study Group clinical trials., Ann. Rheum. Dis., 2011, 70, 8, 1415-1421, doi: 10.1136/ard.2010.145250.
-
Results
Walsh M, Casian A, Flossmann O, Westman K, Höglund P, Pusey C, Jayne DR, , Long-term follow-up of patients with severe ANCA-associated vasculitis comparing plasma exchange to intravenous methylprednisolone treatment is unclear., Kidney Int., 2013, 84, 2, 397-402, doi: 10.1038/ki.2013.131.