CompletedNCT01697267RITAZAREMUpdated Mar 18, 2022Results posted

Rituximab Vasculitis Maintenance Study

A Phase 3 interventional study of Rituximab and Azathioprine in Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis, Microscopic Polyangiitis and Wegener Granulomatosis, sponsored by Cambridge University Hospitals NHS Foundation Trust. Completed at 38 sites in 10 countries. Open to participants aged 15 Years and older. Per ClinicalTrials.gov, last updated 2022-03-18.

Sponsored by Cambridge University Hospitals NHS Foundation Trust · Phase 3, Interventional, and Treatment

Phase: Phase 3
Study type: Interventional
Enrollment: 188
Allocation: Randomized
Ages: 15 Years and older
Sex: All

Study summary

Rituximab is now established as an effective drug for anti-neutrophil cytoplasmic antibody (ANCA) vasculitis following major European and US trials reported in 2010. After a time, its effect wears off and the disease can return. This occurs in at least half of patients within 2 years of receiving Rituximab. A preliminary study in Cambridge has suggested that repeating rituximab every six months stops the disease returning and is safe.

The RITAZAREM trial will find out whether repeating rituximab stops vasculitis returning and whether it works better than the older treatments, azathioprine or methotrexate. It will also tell us how long patients remain well after the repeated rituximab treatments are stopped, and if repeated rituximab is safe. We should also learn useful information about the effects of rituximab on quality of life and economic measures. The trial results will help decide the best treatment for future patients who have their vasculitis initially treated with rituximab.

RITAZAREM aims to recruit patients with established ANCA vasculitis whose disease has come back 'relapsing vasculitis'. All patients will be treated with rituximab and steroids and we anticipate that most will respond well. If their disease is under reasonable control after four months, further treatment with either rituximab (a single dose ever four months for two years) or azathioprine tablets will be chosen randomly. The patients in the rituximab and azathioprine groups will then be compared. Patients will be in the trial for four years.

The study has been designed by members of the European Vasculitis Study group (EUVAS) and the Vasculitis Clinical Research Consortium (VCRC). It will include 190 participants from 30 hospitals in Europe, the USA, Australia and Mexico.

RITAZAREM is being funded by Arthritis Research UK, the U.S. National Institutes of Health and by Roche/Genentech.

Read the detailed description

Patients will be recruited at the time of relapse. All will receive rituximab 375 mg/m2/week x 4 and glucocorticoids.

Those patients that achieve disease control (BVAS/WG ≤ 1 and daily prednisone dose ≤ 10 mg) by month 4 will be randomised to the rituximab or control remission maintenance groups.

Treatment is protocolised for the entire duration of the study, until the common close date, when the final patient recruited has completed 36 months within the study or until the patient has completed 48 months on study whichever the sooner. Patients in the rituximab arm will receive treatment until month 20, and those in the azathioprine arm until month 27.

Conditions studied

Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis
Microscopic Polyangiitis
Wegener Granulomatosis

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Keywords

vasculitis
ANCA vasculitis
microscopic polyangiitis
granulomatosis
Wegener's
AAV
vasculitides

Who can participate

Ages eligible: 15 Years and older
Sexes eligible: All
Accepts healthy volunteers: No

Eligibility criteria

Inclusion Criteria:

A diagnosis of AAV [granulomatosis with polyangiitis or microscopic polyangiitis], according to the definitions of the Chapel Hill Consensus Conference
Current or historical PR3/MPO ANCA positivity by ELISA
Disease relapse defined by one major or three minor disease activity items on the Birmingham Vasculitis Activity Score for Wegeners (BVAS/WG), in patients that have previously achieved remission following at least 3 months of induction therapy, with a combination of glucocorticoids and an immunosuppressive agent (cyclophosphamide or methotrexate or rituximab or mycophenolate mofetil)
Written informed consent

Exclusion Criteria:

Age \< 15 years (age \< 18 years at centres that do not treat paediatric patients)
Exclusions related to medication:
Previous therapy with:
1. Any biological B cell depleting agent (such as rituximab or belimumab) within the past 6 months
2. Alemtuzumab or anti-thymocyte globulin (ATG) within the last 12 months
3. IVIg, infliximab, etanercept, adalimumab, abatacept or plasma exchange in past 3 months
4. Any investigational agent within 28 days of screening, or 5 half lives of the investigational drug (whichever is longer)
Exclusions related to general health:
1. Significant or uncontrolled medical disease not related to AAV, which in the investigators opinion would preclude patient participation
2. Presence of another multisystem autoimmune disease, including Churg Strauss syndrome, systemic lupus erythematosus, anti-GBM disease, or cryoglobulinaemic vasculitis,
3. Any concomitant condition anticipated to likely require greater than 4 weeks per year of oral or systemic glucocorticoid use and which would preclude compliance with the glucocorticoid protocol (e.g. poorly-controlled asthma, COPD, psoriasis, or inflammatory bowel disease).
4. History of severe allergic or anaphylactic reactions to humanised or murine chimeric monoclonal antibodies
5. Known infection with HIV (HIV testing will not be a requirement for trial entry); a past or current history of hepatitis B virus or hepatitis C virus infection.
6. Ongoing or recent (last 12 months) evidence of active tuberculosis or known active infection (screening for tuberculosis is part of "standard of care" in patients with established AAV) or evidence of untreated latent tuberculosis. Screening for tuberculosis is as per local practice.
7. History of malignancy within the past five years or any evidence of persistent malignancy, except fully excised basal cell or squamous cell carcinomas of the skin, or cervical carcinoma in situ which has been treated or excised in a curative procedure.
8. Pregnancy or inadequate contraception in pre-menopausal women
9. Breast feeding or lactating
Exclusion criteria related to laboratory parameters:
1. Bone marrow suppression as evidenced by a total white count \< 4 x109/l, haemoglobin \< 7 gm/dl or platelet count \< 100,000/μl
2. Aspartate aminotransferase or alanine aminotransferase or amylase > 2.5 times the upper limit of normal, unless attributed to vasculitis

Study design

Phase: Phase 3
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 188 participants (actual)

Study arms

Experimental
Rituximab Maintenance
Rituximab maintenance: 1g at 4, 8, 12, 16 \& 20 months with standardised steroid taper
Biological: Rituximab
Active comparator
Azathioprine Maintenance
Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27.
Drug: Azathioprine

Interventions

BiologicalRituximab
Rituximab IV infusion 1000 mg x 1 dose at months 4, 8, 12, 16 and 20 and glucocorticoids. Four - six hour infusion. Treatment with rituximab will cease at month 20.
Also known as: Rituxan, MabThera
DrugAzathioprine
Oral dosage form. Target dose is 2mg/kg; maximum daily dose is 200mg. This should be continued until month 24. The dose should then by reduced by 50% and azathioprine completely withdrawn at month 27. The dose should be rounded down to the nearest 25mg. The dose may vary on alternate days e.g. 100mg one day, 150mg the next for patients on an overall dose of 125mg daily. If patients are aged over 60 years, reduce the dose by 25%. If patients are aged over 75 years, reduce the dose by 50%.
Also known as: Imuran

What researchers measure

Primary outcomes

Relapse-free Survival
The primary efficacy outcome measure of the trial is relapse-free survival, where a relapse is either major or minor. The primary analysis will be a Cox regression model adjusted for the stratification factors (ANCA type, relapse severity and prednisone induction regimen) for the difference in the distribution of relapse-free survival between the rituximab arm and the azathioprine (control) arm (two-sided at α-level of 5%).
Time frame: Any patients who have not relapsed at up to a maximum of 4 years will be censored.

Secondary outcomes

Number of Participants in Remission at 24 and 48 Months
Proportion of patients who maintain remission at 24 and 48 months
Time frame: 24 and 48 months
Combined Damage Assessment Score (Disease Related Damage Assessment)
Cumulative accrual of damage as measured by the combined damage assessment score (CDA). Each persistent or new occurrence of damage is given a score of 1. The cumulative accrual of damage is obtained by summing across the different types of damage to get an overall score (max score = 64).
Time frame: data in Rows represent the change from randomization (month 4) to months 12, 24, 36, and 48.
Cumulative GC Exposure
Cumulative glucocorticoid (GC) exposure during the trial. The trial had a common close out date when the final patient reached month 36 in the trial. Patients were followed until month 48 or the common close out date, whichever happened sooner. Therefore, follow up varied between 36 and 48 months. Cumulative glucocorticoid exposure is presented as a dose in mg for during the treatment period (up to month 24) and across the whole trial (until month 48 or common close out when the final patient reached month 36).
Time frame: Up to 48 months
Severe Adverse Event Rate
Severe adverse event (SAE) rate
Time frame: Up to 48 months
Infection Rates
Infection (treated with intravenous or oral antibiotics) rates
Time frame: Up to 4 years
Health-related Quality of Life Using the SF-36 Physical Composite
The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.
Time frame: 4 months
Health-related Quality of Life Using the SF-36 Mental Composite
The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.
Time frame: 4 months
Health-related Quality of Life Using the SF-36 Physical Composite
The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.
Time frame: 12 months
Health-related Quality of Life Using the SF-36 Mental Composite
The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.
Time frame: 12 months
Health-related Quality of Life Using the SF-36 Physical Composite
The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.
Time frame: 24 months
Health-related Quality of Life Using the SF-36 Mental Composite
The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.
Time frame: 24 months
Health-related Quality of Life Using the SF-36 Physical Composite
The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.
Time frame: 36 months
Health-related Quality of Life Using the SF-36 Mental Composite
The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.
Time frame: 36 months
Health-related Quality of Life Using the SF-36 Physical Composite
The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.
Time frame: 48 months
Health-related Quality of Life Using the SF-36 Mental Composite
The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.
Time frame: 48 months

Results

Posted Mar 18, 2022

Participant flow

Participant flow — Overall Study
Milestone	Rituximab Maintenance	Azathioprine Maintenance
Started	85	85
Month 24	78	78
Completed	71	70
Not completed	14	15
Withdrew: Death	3	1
Withdrew: Withdrawal by subject	5	5
Withdrew: Adverse event	2	1
Withdrew: Lost to follow-up	2	4
Withdrew: Physician decision	2	4

Outcome measures

PrimaryRelapse-free Survival

The primary efficacy outcome measure of the trial is relapse-free survival, where a relapse is either major or minor. The primary analysis will be a Cox regression model adjusted for the stratification factors (ANCA type, relapse severity and prednisone induction regimen) for the difference in the distribution of relapse-free survival between the rituximab arm and the azathioprine (control) arm (two-sided at α-level of 5%).

Time frame:: Any patients who have not relapsed at up to a maximum of 4 years will be censored.
Reported as:: Number · participants

Relapse-free Survival
participants	Rituximab Maintenance	Azathioprine Maintenance
Total number of patients with a relapse	38	60
Total number of patients with a relapse during treatment	13	32
Total number of patients with a relapse post treatment	25	28

SecondaryNumber of Participants in Remission at 24 and 48 Months

Proportion of patients who maintain remission at 24 and 48 months

Time frame:: 24 and 48 months
Reported as:: Count of participants · Participants

Number of Participants in Remission at 24 and 48 Months
Participants	Rituximab Maintenance	Azathioprine Maintenance
Month 24	73	70
Month 48	54	44

SecondaryCombined Damage Assessment Score (Disease Related Damage Assessment)

Cumulative accrual of damage as measured by the combined damage assessment score (CDA). Each persistent or new occurrence of damage is given a score of 1. The cumulative accrual of damage is obtained by summing across the different types of damage to get an overall score (max score = 64).

Time frame:: data in Rows represent the change from randomization (month 4) to months 12, 24, 36, and 48.
Reported as:: Mean · score on a scale

Combined Damage Assessment Score (Disease Related Damage Assessment)
score on a scale	Rituximab Maintenance	Azathioprine Maintenance
Randomisation to month 12	0.275 ± 0.656	0.337 ± 0.610
Randomisation to month 24	0.571 ± 0.909	0.533 ± 0.777
Randomisation to month 36	0.676 ± 0.995	0.899 ± 1.352
Randomisation to month 48	1.09 ± 1.18	1.38 ± 1.65

SecondaryCumulative GC Exposure

Cumulative glucocorticoid (GC) exposure during the trial. The trial had a common close out date when the final patient reached month 36 in the trial. Patients were followed until month 48 or the common close out date, whichever happened sooner. Therefore, follow up varied between 36 and 48 months. Cumulative glucocorticoid exposure is presented as a dose in mg for during the treatment period (up to month 24) and across the whole trial (until month 48 or common close out when the final patient reached month 36).

Time frame:: Up to 48 months
Reported as:: Mean · mg

Cumulative GC Exposure
mg	Rituximab Maintenance	Azathioprine Maintenance
Overall (randomisation to end of trial)	3717 ± 3318	4780 ± 3387
Maintenance treatment period (randomisation to month 24)	2184 ± 1100	2426 ± 1324

SecondarySevere Adverse Event Rate

Severe adverse event (SAE) rate

Time frame:: Up to 48 months
Reported as:: Count of participants · Participants

Severe Adverse Event Rate
Participants	Rituximab Maintenance	Azathioprine Maintenance
Severe Adverse Event Rate	37	48

SecondaryInfection Rates

Infection (treated with intravenous or oral antibiotics) rates

Time frame:: Up to 4 years
Reported as:: Count of participants · Participants

Infection Rates
Participants	Rituximab Maintenance	Azathioprine Maintenance
Infection Rates	54	62

SecondaryHealth-related Quality of Life Using the SF-36 Physical Composite

The 36-Item Short Form Health Survey (SF-36) is a set of generic, coherent, and easily administered quality-of-life measures. Scores for the scale range from 0-100 and transformed to have a mean of 50 and SD of 10 in the reference population, with higher scores indicating a better Health-related Quality of Life.

Time frame:: 4 months
Reported as:: Mean · score on a scale

Health-related Quality of Life Using the SF-36 Physical Composite
score on a scale	Rituximab Maintenance	Azathioprine Maintenance
Health-related Quality of Life Using the SF-36 Physical Composite	36.7 ± 15.4	36.1 ± 14.1

SecondaryHealth-related Quality of Life Using the SF-36 Mental Composite

Time frame:: 4 months
Reported as:: Mean · score on a scale

Health-related Quality of Life Using the SF-36 Mental Composite
score on a scale	Rituximab Maintenance	Azathioprine Maintenance
Health-related Quality of Life Using the SF-36 Mental Composite	51.8 ± 11.3	51.0 ± 11.4

SecondaryHealth-related Quality of Life Using the SF-36 Physical Composite

Time frame:: 12 months
Reported as:: Mean · score on a scale

Health-related Quality of Life Using the SF-36 Physical Composite
score on a scale	Rituximab Maintenance	Azathioprine Maintenance
Health-related Quality of Life Using the SF-36 Physical Composite	38.2 ± 15.2	34.6 ± 15.0

SecondaryHealth-related Quality of Life Using the SF-36 Mental Composite

Time frame:: 12 months
Reported as:: Mean · score on a scale

Health-related Quality of Life Using the SF-36 Mental Composite
score on a scale	Rituximab Maintenance	Azathioprine Maintenance
Health-related Quality of Life Using the SF-36 Mental Composite	50.8 ± 12.4	51.9 ± 11.6

SecondaryHealth-related Quality of Life Using the SF-36 Physical Composite

Time frame:: 24 months
Reported as:: Mean · score on a scale

Health-related Quality of Life Using the SF-36 Physical Composite
score on a scale	Rituximab Maintenance	Azathioprine Maintenance
Health-related Quality of Life Using the SF-36 Physical Composite	36.7 ± 15.8	35.6 ± 14.5

SecondaryHealth-related Quality of Life Using the SF-36 Mental Composite

Time frame:: 24 months
Reported as:: Mean · score on a scale

Health-related Quality of Life Using the SF-36 Mental Composite
score on a scale	Rituximab Maintenance	Azathioprine Maintenance
Health-related Quality of Life Using the SF-36 Mental Composite	51.9 ± 11.9	53.5 ± 10.7

SecondaryHealth-related Quality of Life Using the SF-36 Physical Composite

Time frame:: 36 months
Reported as:: Mean · score on a scale

Health-related Quality of Life Using the SF-36 Physical Composite
score on a scale	Rituximab Maintenance	Azathioprine Maintenance
Health-related Quality of Life Using the SF-36 Physical Composite	34.6 ± 15.9	33.8 ± 15.6

SecondaryHealth-related Quality of Life Using the SF-36 Mental Composite

Time frame:: 36 months
Reported as:: Mean · score on a scale

Health-related Quality of Life Using the SF-36 Mental Composite
score on a scale	Rituximab Maintenance	Azathioprine Maintenance
Health-related Quality of Life Using the SF-36 Mental Composite	52.3 ± 12.5	51.8 ± 10.8

SecondaryHealth-related Quality of Life Using the SF-36 Physical Composite

Time frame:: 48 months
Reported as:: Mean · score on a scale

Health-related Quality of Life Using the SF-36 Physical Composite
score on a scale	Rituximab Maintenance	Azathioprine Maintenance
Health-related Quality of Life Using the SF-36 Physical Composite	35.8 ± 14.9	35.0 ± 16.3

SecondaryHealth-related Quality of Life Using the SF-36 Mental Composite

Time frame:: 48 months
Reported as:: Mean · score on a scale

Health-related Quality of Life Using the SF-36 Mental Composite
score on a scale	Rituximab Maintenance	Azathioprine Maintenance
Health-related Quality of Life Using the SF-36 Mental Composite	50.9 ± 13.0	53.9 ± 9.8

Adverse events

Collected over Adverse events were collected for up to 48 months or until the last patient recruited reached Month 36.. Non-serious events are listed at a 0% frequency threshold.

Adverse event summary by group
Group	Deaths	Serious	Other
Rituximab Maintenance	3/85 (3.5%)	19/85 (22.4%)	42/85 (49.4%)
Azathioprine Maintenance	1/85 (1.2%)	31/85 (36.5%)	43/85 (50.6%)

Most frequent serious events

Showing 10 of 111

Most frequent serious events
Event	Rituximab Maintenance	Azathioprine Maintenance
VasculitisImmune system disorders	4/85	9/85
PneumoniaInfections and infestations	5/85	3/85
Acute kidney injuryRenal and urinary disorders	0/85	4/85
InfluenzaInfections and infestations	2/85	3/85
Respiratory tract infectionInfections and infestations	1/85	3/85
Hip arthroplastySurgical and medical procedures	2/85	3/85
Cardiac failure congestiveCardiac disorders	2/85	0/85
Abdominal painGastrointestinal disorders	2/85	0/85
Chest painGeneral disorders	2/85	0/85
Drug hypersensitivityImmune system disorders	0/85	2/85

Most frequent other events

Showing 10 of 69

Most frequent other events
Event	Rituximab Maintenance	Azathioprine Maintenance
Respiratory tract infectionInfections and infestations	19/85	31/85
Upper respiratory tract infectionInfections and infestations	17/85	17/85
SinusitisInfections and infestations	15/85	10/85
Urinary tract infectionInfections and infestations	9/85	7/85
Lower respiratory tract infectionInfections and infestations	2/85	7/85
CellulitisInfections and infestations	3/85	5/85
Ear infectionInfections and infestations	5/85	4/85
Skin infectionInfections and infestations	5/85	4/85
Haemophilus infectionInfections and infestations	2/85	4/85
Escherichia urinary tract infectionInfections and infestations	3/85	2/85

Baseline characteristics

Age, Categorical
Age, Categorical(Participants)	Rituximab Maintenance	Azathioprine Maintenance	Total
<=18 years	0	0	0
Between 18 and 65 years	54	51	105
>=65 years	31	34	65

Age, Continuous
Age, Continuous(years)	Rituximab Maintenance	Azathioprine Maintenance	Total
Mean	57.1 ± 15.1	58.6 ± 13.9	57.8 ± 14.5

Sex: Female, Male
Sex: Female, Male(Participants)	Rituximab Maintenance	Azathioprine Maintenance	Total
Female	42	44	86
Male	43	41	84

Race/Ethnicity, Customized
Race/Ethnicity, Customized(Participants)	Rituximab Maintenance	Azathioprine Maintenance	Total
White	78	77	155
Black	0	0	0
Asian	5	5	10
Hispanic	2	1	3
Other	0	2	2

Region of Enrollment
Region of Enrollment(Participants)	Rituximab Maintenance	Azathioprine Maintenance	Total
Canada	13	11	24
Sweden	3	2	5
United States	26	22	48
Czechia	0	1	1
Japan	2	2	4
United Kingdom	36	42	78
Australia	5	5	10

ANCA type
ANCA type(Participants)	Rituximab Maintenance	Azathioprine Maintenance	Total
anti-PR3	61	62	123
anti-MPO	24	23	47

Prednisone Induction Regimen
Prednisone Induction Regimen(Participants)	Rituximab Maintenance	Azathioprine Maintenance	Total
1A (starting dose 1mg/kg/day)	24	24	48
1B (starting dose 0.5mg/kg/day)	61	61	122

Relapse type
Relapse type(Participants)	Rituximab Maintenance	Azathioprine Maintenance	Total
Severe	52	54	106
Non-severe	33	31	64

Study locations

38 sites

Cedars-Sinai Medical Center
Los Angeles, California 90048, United States
University of Michigan
Ann Arbor, Michigan 48109, United States
Mayo Clinic
Rochester, Minnesota 55905, United States
Hospital for Special Surgery
New York, New York 10021, United States
University of North Carolina
Chapel Hill, North Carolina 27599, United States
Cleveland Clinic
Cleveland, Ohio 44195, United States
University of Pennsylvania
Philadelphia, Pennsylvania 19104, United States
University of Pittsburgh
Pittsburgh, Pennsylvania 15260, United States
University of Utah
Salt Lake City, Utah 84112, United States
Canberra Hospital
Garran, Australian Capital Territory, Australia
Royal Brisbane & Women's Hospital
Herston, Queensland 4029, Australia
Royal Adelaide Hospital
Adelaide, South Australia, Australia
St. Joseph's Healthcare
Hamilton, Ontario L8N 4A6, Canada
Mount Sinai Hospital
Toronto, Ontario M5T 3L9, Canada
General Faculty Hospital
Prague, Czechia
Cork University Hospital
Cork, Ireland
University Hospital of Parma
Parma, 43100, Italy
Okayama University
Kita-ku, Okayama 700-0082, Japan
Chiba University
Chiba-shi, 263-8522, Japan
Kitano Hospital
Kyoto, 606-8501, Japan
University of Miyazaki
Miyazaki, 889-2192, Japan
Teikyo University
Tokyo, 173-0003, Japan
Tokyo Metropolitan Geriatric
Tokyo, 173-0015, Japan
Kyorin University school of medicine
Tokyo, 192-0005, Japan
Auckland City Hospital
Grafton, Auckland 1023, New Zealand
North Shore Hospital
Westlake, Auckland, New Zealand
Karolinska University Hospital
Stockholm, Sweden
Leicester General Hospital
Leicester, Leicestershire LE5 4PW, United Kingdom
Queen Elizabeth Hospital
Birmingham, B15 2WB, United Kingdom
Brighton and Sussex University Hospitals
Brighton, BN2 5BE, United Kingdom
Addenbrooke's Hospital
Cambridge, CB2 0QQ, United Kingdom
Russells Hall Hospital
Dudley, DY1 2HQ, United Kingdom
Ipswich Hospital
Ipswich, IP4 5PD, United Kingdom
Chapel Allerton Hospital
Leeds, LS7 4SA, United Kingdom
Imperial College
London, W12 0NN, United Kingdom
James Cook University Hospital
Middlesbrough, TS4 3BW, United Kingdom
Queen's Medical Centre Campus, Nottingham University Hosp
Nottingham, NG7 2UH, United Kingdom
University of Oxford
Oxford, OX1 2JD, United Kingdom

References and documents

Publications

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Watts RA, Scott DG. Epidemiology of the vasculitides. Curr Opin Rheumatol. 2003 Jan;15(1):11-6. doi: 10.1097/00002281-200301000-00003. PubMed 12496504 ↗
Booth AD, Almond MK, Burns A, Ellis P, Gaskin G, Neild GH, Plaisance M, Pusey CD, Jayne DR; Pan-Thames Renal Research Group. Outcome of ANCA-associated renal vasculitis: a 5-year retrospective study. Am J Kidney Dis. 2003 Apr;41(4):776-84. doi: 10.1016/s0272-6386(03)00025-8. PubMed 12666064 ↗
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De Groot K, Rasmussen N, Bacon PA, Tervaert JW, Feighery C, Gregorini G, Gross WL, Luqmani R, Jayne DR. 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. doi: 10.1002/art.21142. PubMed 16052573 ↗
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Seo P, Min YI, Holbrook JT, Hoffman GS, Merkel PA, Spiera R, Davis JC, Ytterberg SR, St Clair EW, McCune WJ, Specks U, Allen NB, Luqmani RA, Stone JH; WGET Research Group. Damage caused by Wegener's granulomatosis and its treatment: prospective data from the Wegener's Granulomatosis Etanercept Trial (WGET). Arthritis Rheum. 2005 Jul;52(7):2168-78. doi: 10.1002/art.21117. PubMed 15986348 ↗
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Jones RB, Tervaert JW, Hauser T, Luqmani R, Morgan MD, Peh CA, Savage CO, Segelmark M, Tesar V, van Paassen P, Walsh D, Walsh M, Westman K, Jayne DR; European Vasculitis Study Group. Rituximab versus cyclophosphamide in ANCA-associated renal vasculitis. N Engl J Med. 2010 Jul 15;363(3):211-20. doi: 10.1056/NEJMoa0909169. PubMed 20647198 ↗
Stone JH, Merkel PA, Spiera R, Seo P, Langford CA, Hoffman GS, Kallenberg CG, St Clair EW, Turkiewicz A, Tchao NK, Webber L, Ding L, Sejismundo LP, Mieras K, Weitzenkamp D, Ikle D, Seyfert-Margolis V, Mueller M, Brunetta P, Allen NB, Fervenza FC, Geetha D, Keogh KA, Kissin EY, Monach PA, Peikert T, Stegeman C, Ytterberg SR, Specks U; RAVE-ITN Research Group. Rituximab versus cyclophosphamide for ANCA-associated vasculitis. N Engl J Med. 2010 Jul 15;363(3):221-32. doi: 10.1056/NEJMoa0909905. PubMed 20647199 ↗
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Study documents

Study protocol · Jul 12, 2019
Statistical analysis plan · Jan 25, 2021

Documents are hosted by the registry — open the source record to download them.

Individual participant data

Plan to share: No

Registry details

Key details

Study ID: NCT01697267
Lead sponsor: Cambridge University Hospitals NHS Foundation Trust
Collaborators: Arthritis Research UK, Roche Pharma AG, Genentech, Inc., University of Pennsylvania
Responsible party: David Jayne (Director, Vasculitis and Lupus Clinic, Cambridge University Hospitals NHS Foundation Trust) — Principal investigator
First posted: Oct 2, 2012
Start date: Apr 2013
Primary completion: Nov 22, 2018
Completion: Nov 21, 2019
Results posted: Mar 18, 2022
Last update: Mar 18, 2022

Study contacts

David Jayne

study chair · Cambridge University Hospitals NHS Foundation Trust

Peter Merkel

study chair · University of Pennsylvania

Oversight

Data monitoring committee: Yes

View the source record on ClinicalTrials.gov ↗

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