RITAZAREM: Rituximab Vasculitis Maintenance Study
Sponsor
Cambridge University Hospitals NHS Foundation Trust (Other)
Overall Status
Completed
CT.gov ID
NCT01697267
Collaborator
Arthritis Research UK (Other), Roche Pharma AG (Industry), Genentech, Inc. (Industry), University of Pennsylvania (Other)
188
38
2
79.7
4.9
0.1
Study Details
Study Description
Brief 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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 3 |
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.
Study Design
Study Type:
Interventional
Actual Enrollment
:
188 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
An International, Open Label, Randomised Controlled Trial Comparing Rituximab With Azathioprine as Maintenance Therapy in Relapsing ANCA-associated Vasculitis
Actual Study Start Date
:
Apr 1, 2013
Actual Primary Completion Date
:
Nov 22, 2018
Actual Study Completion Date
:
Nov 21, 2019
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Rituximab Maintenance Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper |
Biological: Rituximab
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.
Other Names:
|
| 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
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%.
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Relapse-free Survival [Any patients who have not relapsed at up to a maximum of 4 years will be censored.]
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%).
Secondary Outcome Measures
- Number of Participants in Remission at 24 and 48 Months [24 and 48 months]
Proportion of patients who maintain remission at 24 and 48 months
- Combined Damage Assessment Score (Disease Related Damage Assessment) [data in Rows represent the change from randomization (month 4) to months 12, 24, 36, and 48.]
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).
- Cumulative GC Exposure [Up to 48 months]
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).
- Severe Adverse Event Rate [Up to 48 months]
Severe adverse event (SAE) rate
- Infection Rates [Up to 4 years]
Infection (treated with intravenous or oral antibiotics) rates
- Health-related Quality of Life Using the SF-36 Physical Composite [4 months]
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.
- Health-related Quality of Life Using the SF-36 Mental Composite [4 months]
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.
- Health-related Quality of Life Using the SF-36 Physical Composite [12 months]
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.
- Health-related Quality of Life Using the SF-36 Mental Composite [12 months]
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.
- Health-related Quality of Life Using the SF-36 Physical Composite [24 months]
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.
- Health-related Quality of Life Using the SF-36 Mental Composite [24 months]
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.
- Health-related Quality of Life Using the SF-36 Physical Composite [36 months]
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.
- Health-related Quality of Life Using the SF-36 Mental Composite [36 months]
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.
- Health-related Quality of Life Using the SF-36 Physical Composite [48 months]
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.
- Health-related Quality of Life Using the SF-36 Mental Composite [48 months]
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.
Eligibility Criteria
Criteria
Ages Eligible for Study:
15 Years
and Older
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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:
-
Any biological B cell depleting agent (such as rituximab or belimumab) within the past 6 months
-
Alemtuzumab or anti-thymocyte globulin (ATG) within the last 12 months
-
IVIg, infliximab, etanercept, adalimumab, abatacept or plasma exchange in past 3 months
-
Any investigational agent within 28 days of screening, or 5 half lives of the investigational drug (whichever is longer)
-
Exclusions related to general health:
-
Significant or uncontrolled medical disease not related to AAV, which in the investigators opinion would preclude patient participation
-
Presence of another multisystem autoimmune disease, including Churg Strauss syndrome, systemic lupus erythematosus, anti-GBM disease, or cryoglobulinaemic vasculitis,
-
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).
-
History of severe allergic or anaphylactic reactions to humanised or murine chimeric monoclonal antibodies
-
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.
-
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.
-
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.
-
Pregnancy or inadequate contraception in pre-menopausal women
-
Breast feeding or lactating
-
Exclusion criteria related to laboratory parameters:
-
Bone marrow suppression as evidenced by a total white count < 4 x109/l, haemoglobin < 7 gm/dl or platelet count < 100,000/μl
-
Aspartate aminotransferase or alanine aminotransferase or amylase > 2.5 times the upper limit of normal, unless attributed to vasculitis
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Cedars-Sinai Medical Center | Los Angeles | California | United States | 90048 |
| 2 | University of Michigan | Ann Arbor | Michigan | United States | 48109 |
| 3 | Mayo Clinic | Rochester | Minnesota | United States | 55905 |
| 4 | Hospital for Special Surgery | New York | New York | United States | 10021 |
| 5 | University of North Carolina | Chapel Hill | North Carolina | United States | 27599 |
| 6 | Cleveland Clinic | Cleveland | Ohio | United States | 44195 |
| 7 | University of Pennsylvania | Philadelphia | Pennsylvania | United States | 19104 |
| 8 | University of Pittsburgh | Pittsburgh | Pennsylvania | United States | 15260 |
| 9 | University of Utah | Salt Lake City | Utah | United States | 84112 |
| 10 | Canberra Hospital | Garran | Australian Capital Territory | Australia | |
| 11 | Royal Brisbane & Women's Hospital | Herston | Queensland | Australia | 4029 |
| 12 | Royal Adelaide Hospital | Adelaide | South Australia | Australia | |
| 13 | St. Joseph's Healthcare | Hamilton | Ontario | Canada | L8N 4A6 |
| 14 | Mount Sinai Hospital | Toronto | Ontario | Canada | M5T 3L9 |
| 15 | General Faculty Hospital | Prague | Czechia | ||
| 16 | Cork University Hospital | Cork | Ireland | ||
| 17 | University Hospital of Parma | Parma | Italy | 43100 | |
| 18 | Okayama University | Kita-ku | Okayama | Japan | 700-0082 |
| 19 | Chiba University | Chiba-shi | Japan | 263-8522 | |
| 20 | Kitano Hospital | Kyoto | Japan | 606-8501 | |
| 21 | University of Miyazaki | Miyazaki | Japan | 889-2192 | |
| 22 | Teikyo University | Tokyo | Japan | 173-0003 | |
| 23 | Tokyo Metropolitan Geriatric | Tokyo | Japan | 173-0015 | |
| 24 | Kyorin University school of medicine | Tokyo | Japan | 192-0005 | |
| 25 | Auckland City Hospital | Grafton | Auckland | New Zealand | 1023 |
| 26 | North Shore Hospital | Westlake | Auckland | New Zealand | |
| 27 | Karolinska University Hospital | Stockholm | Sweden | ||
| 28 | Leicester General Hospital | Leicester | Leicestershire | United Kingdom | LE5 4PW |
| 29 | Queen Elizabeth Hospital | Birmingham | United Kingdom | B15 2WB | |
| 30 | Brighton and Sussex University Hospitals | Brighton | United Kingdom | BN2 5BE | |
| 31 | Addenbrooke's Hospital | Cambridge | United Kingdom | CB2 0QQ | |
| 32 | Russells Hall Hospital | Dudley | United Kingdom | DY1 2HQ | |
| 33 | Ipswich Hospital | Ipswich | United Kingdom | IP4 5PD | |
| 34 | Chapel Allerton Hospital | Leeds | United Kingdom | LS7 4SA | |
| 35 | Imperial College | London | United Kingdom | W12 0NN | |
| 36 | James Cook University Hospital | Middlesbrough | United Kingdom | TS4 3BW | |
| 37 | Queen's Medical Centre Campus, Nottingham University Hosp | Nottingham | United Kingdom | NG7 2UH | |
| 38 | University of Oxford | Oxford | United Kingdom | OX1 2JD |
Sponsors and Collaborators
- Cambridge University Hospitals NHS Foundation Trust
- Arthritis Research UK
- Roche Pharma AG
- Genentech, Inc.
- University of Pennsylvania
Investigators
- Study Chair: David Jayne, Cambridge University Hospitals NHS Foundation Trust
- Study Chair: Peter Merkel, University of Pennsylvania
Study Documents (Full-Text)
More Information
Publications
- 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. Review.
- de Groot K, Harper L, Jayne DR, Flores Suarez LF, Gregorini G, Gross WL, Luqmani R, Pusey CD, Rasmussen N, Sinico RA, Tesar V, Vanhille P, Westman K, Savage CO; EUVAS (European Vasculitis Study Group). 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.
- 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.
- Falk RJ, Jennette JC. ANCA disease: where is this field heading? J Am Soc Nephrol. 2010 May;21(5):745-52. doi: 10.1681/ASN.2009121238. Epub 2010 Apr 15. Review.
- Jayne D, Rasmussen N, Andrassy K, Bacon P, Tervaert JW, Dadoniené J, Ekstrand A, Gaskin G, Gregorini G, de Groot K, Gross W, Hagen EC, Mirapeix E, Pettersson E, Siegert C, Sinico A, Tesar V, Westman K, Pusey C; European Vasculitis Study Group. A randomized trial of maintenance therapy for vasculitis associated with antineutrophil cytoplasmic autoantibodies. N Engl J Med. 2003 Jul 3;349(1):36-44.
- Jones RB, Ferraro AJ, Chaudhry AN, Brogan P, Salama AD, Smith KG, Savage CO, Jayne DR. A multicenter survey of rituximab therapy for refractory antineutrophil cytoplasmic antibody-associated vasculitis. Arthritis Rheum. 2009 Jul;60(7):2156-68. doi: 10.1002/art.24637.
- 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.
- Reff ME, Carner K, Chambers KS, Chinn PC, Leonard JE, Raab R, Newman RA, Hanna N, Anderson DR. Depletion of B cells in vivo by a chimeric mouse human monoclonal antibody to CD20. Blood. 1994 Jan 15;83(2):435-45.
- 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.
- 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.
- Watts RA, Scott DG. Epidemiology of the vasculitides. Curr Opin Rheumatol. 2003 Jan;15(1):11-6. Review.
- Watts RA, Suppiah R, Merkel PA, Luqmani R. Systemic vasculitis--is it time to reclassify? Rheumatology (Oxford). 2011 Apr;50(4):643-5. doi: 10.1093/rheumatology/keq229. Epub 2010 Jul 20.
- Wegener's Granulomatosis Etanercept Trial (WGET) Research Group. Etanercept plus standard therapy for Wegener's granulomatosis. N Engl J Med. 2005 Jan 27;352(4):351-61.
Responsible Party:
David Jayne,
Director, Vasculitis and Lupus Clinic,
Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01697267
Other Study ID Numbers:
- RITAZAREM
- 2012-001102-14
First Posted:
Oct 2, 2012
Last Update Posted:
Mar 18, 2022
Last Verified:
Feb 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Keywords provided by David Jayne,
Director, Vasculitis and Lupus Clinic,
Cambridge University Hospitals NHS Foundation Trust
Additional relevant MeSH terms:
Study Results
Participant Flow
| Recruitment Details | |
|---|---|
| Pre-assignment Detail | Of 188 enrolled participants, 170 met the criteria for randomisation and were randomised for treatment. |
| Arm/Group Title | Rituximab Maintenance | Azathioprine Maintenance |
|---|---|---|
| Arm/Group Description | Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: 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. | Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: 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%. |
| Period Title: Overall Study | ||
| STARTED | 85 | 85 |
| Month 24 | 78 | 78 |
| COMPLETED | 71 | 70 |
| NOT COMPLETED | 14 | 15 |
Baseline Characteristics
| Arm/Group Title | Rituximab Maintenance | Azathioprine Maintenance | Total |
|---|---|---|---|
| Arm/Group Description | Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: 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. | Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: 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%. | Total of all reporting groups |
| Overall Participants | 85 | 85 | 170 |
| Age (Count of Participants) | |||
| <=18 years |
0
0%
|
0
0%
|
0
0%
|
| Between 18 and 65 years |
54
63.5%
|
51
60%
|
105
61.8%
|
| >=65 years |
31
36.5%
|
34
40%
|
65
38.2%
|
| Age (years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [years] |
57.1
(15.1)
|
58.6
(13.9)
|
57.8
(14.5)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
42
49.4%
|
44
51.8%
|
86
50.6%
|
| Male |
43
50.6%
|
41
48.2%
|
84
49.4%
|
| Race/Ethnicity, Customized (Count of Participants) | |||
| White |
78
91.8%
|
77
90.6%
|
155
91.2%
|
| Black |
0
0%
|
0
0%
|
0
0%
|
| Asian |
5
5.9%
|
5
5.9%
|
10
5.9%
|
| Hispanic |
2
2.4%
|
1
1.2%
|
3
1.8%
|
| Other |
0
0%
|
2
2.4%
|
2
1.2%
|
| Region of Enrollment (Count of Participants) | |||
| Canada |
13
15.3%
|
11
12.9%
|
24
14.1%
|
| Sweden |
3
3.5%
|
2
2.4%
|
5
2.9%
|
| United States |
26
30.6%
|
22
25.9%
|
48
28.2%
|
| Czechia |
0
0%
|
1
1.2%
|
1
0.6%
|
| Japan |
2
2.4%
|
2
2.4%
|
4
2.4%
|
| United Kingdom |
36
42.4%
|
42
49.4%
|
78
45.9%
|
| Australia |
5
5.9%
|
5
5.9%
|
10
5.9%
|
| ANCA type (Count of Participants) | |||
| anti-PR3 |
61
71.8%
|
62
72.9%
|
123
72.4%
|
| anti-MPO |
24
28.2%
|
23
27.1%
|
47
27.6%
|
| Prednisone Induction Regimen (Count of Participants) | |||
| 1A (starting dose 1mg/kg/day) |
24
28.2%
|
24
28.2%
|
48
28.2%
|
| 1B (starting dose 0.5mg/kg/day) |
61
71.8%
|
61
71.8%
|
122
71.8%
|
| Relapse type (Count of Participants) | |||
| Severe |
52
61.2%
|
54
63.5%
|
106
62.4%
|
| Non-severe |
33
38.8%
|
31
36.5%
|
64
37.6%
|
Outcome Measures
| Title | Relapse-free Survival |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rituximab Maintenance | Azathioprine Maintenance |
|---|---|---|
| Arm/Group Description | Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: 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. | Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: 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%. |
| Measure Participants | 85 | 85 |
| Total number of patients with a relapse |
38
44.7%
|
60
70.6%
|
| Total number of patients with a relapse during treatment |
13
15.3%
|
32
37.6%
|
| Total number of patients with a relapse post treatment |
25
29.4%
|
28
32.9%
|
| Title | Number of Participants in Remission at 24 and 48 Months |
|---|---|
| Description | Proportion of patients who maintain remission at 24 and 48 months |
| Time Frame | 24 and 48 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rituximab Maintenance | Azathioprine Maintenance |
|---|---|---|
| Arm/Group Description | Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: 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. | Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: 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%. |
| Measure Participants | 85 | 85 |
| Month 24 |
73
85.9%
|
70
82.4%
|
| Month 48 |
54
63.5%
|
44
51.8%
|
| Title | Combined Damage Assessment Score (Disease Related Damage Assessment) |
|---|---|
| Description | 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. |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rituximab Maintenance | Azathioprine Maintenance |
|---|---|---|
| Arm/Group Description | Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: 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. | Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: 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%. |
| Measure Participants | 85 | 85 |
| 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)
|
| Title | Cumulative GC Exposure |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rituximab Maintenance | Azathioprine Maintenance |
|---|---|---|
| Arm/Group Description | Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: 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. | Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: 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%. |
| Measure Participants | 85 | 85 |
| Overall (randomisation to end of trial) |
3717
(3318)
|
4780
(3387)
|
| Maintenance treatment period (randomisation to month 24) |
2184
(1100)
|
2426
(1324)
|
| Title | Severe Adverse Event Rate |
|---|---|
| Description | Severe adverse event (SAE) rate |
| Time Frame | Up to 48 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rituximab Maintenance | Azathioprine Maintenance |
|---|---|---|
| Arm/Group Description | Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: 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. | Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: 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%. |
| Measure Participants | 85 | 85 |
| Count of Participants [Participants] |
37
43.5%
|
48
56.5%
|
| Title | Infection Rates |
|---|---|
| Description | Infection (treated with intravenous or oral antibiotics) rates |
| Time Frame | Up to 4 years |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rituximab Maintenance | Azathioprine Maintenance |
|---|---|---|
| Arm/Group Description | Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: 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. | Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: 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%. |
| Measure Participants | 85 | 85 |
| Count of Participants [Participants] |
54
63.5%
|
62
72.9%
|
| Title | Health-related Quality of Life Using the SF-36 Physical Composite |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rituximab Maintenance | Azathioprine Maintenance |
|---|---|---|
| Arm/Group Description | Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: 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. | Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: 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%. |
| Measure Participants | 83 | 81 |
| Mean (Standard Deviation) [score on a scale] |
36.7
(15.4)
|
36.1
(14.1)
|
| Title | Health-related Quality of Life Using the SF-36 Mental Composite |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rituximab Maintenance | Azathioprine Maintenance |
|---|---|---|
| Arm/Group Description | Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: 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. | Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: 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%. |
| Measure Participants | 83 | 81 |
| Mean (Standard Deviation) [score on a scale] |
51.8
(11.3)
|
51.0
(11.4)
|
| Title | Health-related Quality of Life Using the SF-36 Physical Composite |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rituximab Maintenance | Azathioprine Maintenance |
|---|---|---|
| Arm/Group Description | Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: 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. | Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: 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%. |
| Measure Participants | 80 | 80 |
| Mean (Standard Deviation) [score on a scale] |
38.2
(15.2)
|
34.6
(15.0)
|
| Title | Health-related Quality of Life Using the SF-36 Mental Composite |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rituximab Maintenance | Azathioprine Maintenance |
|---|---|---|
| Arm/Group Description | Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: 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. | Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: 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%. |
| Measure Participants | 80 | 80 |
| Mean (Standard Deviation) [score on a scale] |
50.8
(12.4)
|
51.9
(11.6)
|
| Title | Health-related Quality of Life Using the SF-36 Physical Composite |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rituximab Maintenance | Azathioprine Maintenance |
|---|---|---|
| Arm/Group Description | Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: 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. | Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: 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%. |
| Measure Participants | 77 | 70 |
| Mean (Standard Deviation) [score on a scale] |
36.7
(15.8)
|
35.6
(14.5)
|
| Title | Health-related Quality of Life Using the SF-36 Mental Composite |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rituximab Maintenance | Azathioprine Maintenance |
|---|---|---|
| Arm/Group Description | Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: 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. | Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: 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%. |
| Measure Participants | 77 | 70 |
| Mean (Standard Deviation) [score on a scale] |
51.9
(11.9)
|
53.5
(10.7)
|
| Title | Health-related Quality of Life Using the SF-36 Physical Composite |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rituximab Maintenance | Azathioprine Maintenance |
|---|---|---|
| Arm/Group Description | Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: 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. | Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: 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%. |
| Measure Participants | 74 | 69 |
| Mean (Standard Deviation) [score on a scale] |
34.6
(15.9)
|
33.8
(15.6)
|
| Title | Health-related Quality of Life Using the SF-36 Mental Composite |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rituximab Maintenance | Azathioprine Maintenance |
|---|---|---|
| Arm/Group Description | Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: 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. | Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: 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%. |
| Measure Participants | 74 | 69 |
| Mean (Standard Deviation) [score on a scale] |
52.3
(12.5)
|
51.8
(10.8)
|
| Title | Health-related Quality of Life Using the SF-36 Physical Composite |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rituximab Maintenance | Azathioprine Maintenance |
|---|---|---|
| Arm/Group Description | Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: 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. | Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: 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%. |
| Measure Participants | 55 | 51 |
| Mean (Standard Deviation) [score on a scale] |
35.8
(14.9)
|
35.0
(16.3)
|
| Title | Health-related Quality of Life Using the SF-36 Mental Composite |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Rituximab Maintenance | Azathioprine Maintenance |
|---|---|---|
| Arm/Group Description | Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: 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. | Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: 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%. |
| Measure Participants | 55 | 51 |
| Mean (Standard Deviation) [score on a scale] |
50.9
(13.0)
|
53.9
(9.8)
|
Adverse Events
| Time Frame | Adverse events were collected for up to 48 months or until the last patient recruited reached Month 36. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Rituximab Maintenance | Azathioprine Maintenance | ||
| Arm/Group Description | Rituximab maintenance: 1g at 4, 8, 12, 16 & 20 months with standardised steroid taper Rituximab: 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. | Azathioprine Maintenance: 2mg/kg/day with standardised steroid taper, from month 4 (randomisation) (200 mg maximum daily dose). Azathioprine withdrawn at month 27. Azathioprine: 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%. | ||
All Cause Mortality |
||||
| Rituximab Maintenance | Azathioprine Maintenance | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 3/85 (3.5%) | 1/85 (1.2%) | ||
Serious Adverse Events |
||||
| Rituximab Maintenance | Azathioprine Maintenance | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 19/85 (22.4%) | 31/85 (36.5%) | ||
| Blood and lymphatic system disorders | ||||
| Iron deficiency anaemia | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Neutropenia | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Cardiac disorders | ||||
| Atrial fibrillation | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Atrioventricular block complete | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Cardiac failure congestive | 2/85 (2.4%) | 2 | 0/85 (0%) | 0 |
| Cardiomyopathy | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Coronary artery disease | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Myocardial infarction | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Eye disorders | ||||
| Periorbital oedema | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Gastrointestinal disorders | ||||
| Abdominal pain | 2/85 (2.4%) | 2 | 0/85 (0%) | 0 |
| Oesophageal spasm | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Oesophagitis | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Pancreatitis | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Small intestinal obstruction | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Enterovesical fistula | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| General disorders | ||||
| Chest pain | 2/85 (2.4%) | 2 | 0/85 (0%) | 0 |
| Pyrexia | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Perforated ulcer | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Stenosis | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Hepatobiliary disorders | ||||
| Cholecystitis | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Cholecystitis acute | 1/85 (1.2%) | 1 | 1/85 (1.2%) | 1 |
| Cholelithiasis | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Immune system disorders | ||||
| Drug hypersensitivity | 0/85 (0%) | 0 | 2/85 (2.4%) | 2 |
| Pulmonary vasculitis | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Vasculitis | 4/85 (4.7%) | 13 | 9/85 (10.6%) | 13 |
| Infections and infestations | ||||
| Appendicitis | 2/85 (2.4%) | 2 | 1/85 (1.2%) | 1 |
| Bronchitis | 1/85 (1.2%) | 1 | 2/85 (2.4%) | 2 |
| Cellulitis | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Dacryocystitis | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Diverticulitis | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Gastroenteritis viral | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Influenza | 2/85 (2.4%) | 2 | 3/85 (3.5%) | 3 |
| Lower respiratory tract infection | 0/85 (0%) | 0 | 2/85 (2.4%) | 2 |
| Peritonitis | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Pneumonia | 5/85 (5.9%) | 5 | 3/85 (3.5%) | 3 |
| Pneumonia klebsiella | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Pneumonia viral | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Sepsis | 2/85 (2.4%) | 2 | 0/85 (0%) | 0 |
| Sinusitis | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Urinary tract infection | 1/85 (1.2%) | 1 | 2/85 (2.4%) | 2 |
| Escherichia urinary tract infection | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Periorbital abscess | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Infective exacerbation of chronic obstructive airways disease | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Respiratory tract infection | 1/85 (1.2%) | 1 | 3/85 (3.5%) | 3 |
| Metapneumovirus infection | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Oral herpes | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Injury, poisoning and procedural complications | ||||
| Accident | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Fall | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Subdural haematoma | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Post procedural complication | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Intra-abdominal haemorrhage | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Vascular access complication | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Investigations | ||||
| Medical observation | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Transaminases increased | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Metabolism and nutrition disorders | ||||
| Dehydration | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Hyperglycaemia | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Hyperkalaemia | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Metabolic acidosis | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Musculoskeletal and connective tissue disorders | ||||
| Myasthenia gravis | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Osteoarthritis | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Intervertebral disc protrusion | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Myasthenia gravis crisis | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Pubis fracture | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Bladder papilloma | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Lung adenocarcinoma | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Pancreatic carcinoma metastatic | 1/85 (1.2%) | 1 | 1/85 (1.2%) | 1 |
| Sarcoma of skin | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Squamous cell carcinoma | 1/85 (1.2%) | 1 | 1/85 (1.2%) | 1 |
| Colon neoplasm 1 | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Anal squamous cell carcinoma | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Nervous system disorders | ||||
| Haemorrhagic stroke | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Sleep apnoea syndrome | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Subdural haemorrhage | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Psychiatric disorders | ||||
| Conversion disorder | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Renal and urinary disorders | ||||
| Nephrolithiasis | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Proteinuria | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Renal impairment | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Acute kidney injury | 0/85 (0%) | 0 | 4/85 (4.7%) | 4 |
| Respiratory, thoracic and mediastinal disorders | ||||
| Bronchospasm | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Chronic obstructive pulmonary disease | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Dyspnoea | 0/85 (0%) | 0 | 2/85 (2.4%) | 2 |
| Laryngeal stenosis | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Pneumonitis | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Pneumothorax | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Stridor | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Pneumomediastinum | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Surgical and medical procedures | ||||
| Aortic valve replacement | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Bunion operation | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Cholecystectomy | 1/85 (1.2%) | 1 | 1/85 (1.2%) | 1 |
| Colostomy closure | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Dacryocystorhinostomy | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Hip arthroplasty | 2/85 (2.4%) | 2 | 3/85 (3.5%) | 3 |
| Knee arthroplasty | 2/85 (2.4%) | 2 | 1/85 (1.2%) | 1 |
| Lung lobectomy | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Renal transplant | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Spinal decompression | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Renal and pancreas transplant | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Sigmoidectomy | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Cardiac ablation | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Infusion | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Colporrhaphy | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Thyroidectomy | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Joint resurfacing surgery | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Vascular anastomosis | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Vascular disorders | ||||
| Epistaxis | 0/85 (0%) | 0 | 2/85 (2.4%) | 2 |
| Haemoptysis | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Orthostatic hypotension | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Pulmonary embolism | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Vascular injury | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Vascular pseudoaneurysm | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Haemorrhage | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
Other (Not Including Serious) Adverse Events |
||||
| Rituximab Maintenance | Azathioprine Maintenance | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 42/85 (49.4%) | 43/85 (50.6%) | ||
| General disorders | ||||
| Malaise | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Hepatobiliary disorders | ||||
| Cholecystitis | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Infections and infestations | ||||
| Bacterial dacryocystitis | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Bacterial infection | 2/85 (2.4%) | 2 | 0/85 (0%) | 0 |
| Beta haemolytic streptococcal infection | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Bronchitis haemophilus | 2/85 (2.4%) | 2 | 0/85 (0%) | 0 |
| Cellulitis | 3/85 (3.5%) | 3 | 5/85 (5.9%) | 5 |
| Cellulitis orbital | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Citrobacter infection | 1/85 (1.2%) | 1 | 1/85 (1.2%) | 1 |
| Cystitis escherichia | 1/85 (1.2%) | 1 | 2/85 (2.4%) | 2 |
| Cystitis klebsiella | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Enterococcal infection | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Escherichia urinary tract infection | 3/85 (3.5%) | 3 | 2/85 (2.4%) | 2 |
| Haemophilus infection | 2/85 (2.4%) | 2 | 4/85 (4.7%) | 4 |
| Klebsiella infection | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Pneumonia haemophilus | 1/85 (1.2%) | 1 | 1/85 (1.2%) | 1 |
| Pneumonia klebsiella | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Pneumonia pneumococca | 2/85 (2.4%) | 2 | 0/85 (0%) | 0 |
| Pneumonia pseudomonal | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Proteus infection | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Pseudomonas bronchitis | 2/85 (2.4%) | 2 | 1/85 (1.2%) | 1 |
| Pseudomonas infection | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Staphylococcal impetigo | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Staphylococcal infection | 3/85 (3.5%) | 3 | 2/85 (2.4%) | 2 |
| Tonsillitis bacterial | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Urinary tract infection enterococcal | 2/85 (2.4%) | 2 | 1/85 (1.2%) | 1 |
| Body tinea | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Candida infection | 1/85 (1.2%) | 1 | 1/85 (1.2%) | 1 |
| Oesophageal candidiasis | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Oral candidiasis | 2/85 (2.4%) | 2 | 1/85 (1.2%) | 1 |
| Tinea infection | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Tinea pedis | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Vulvovaginal candidiasis | 1/85 (1.2%) | 1 | 2/85 (2.4%) | 2 |
| Vulvovaginal mycotic infection | 2/85 (2.4%) | 2 | 0/85 (0%) | 0 |
| Bronchitis | 2/85 (2.4%) | 2 | 0/85 (0%) | 0 |
| Conjunctivitis | 2/85 (2.4%) | 2 | 2/85 (2.4%) | 2 |
| Cystitis | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Diverticulitis | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Ear infection | 5/85 (5.9%) | 5 | 4/85 (4.7%) | 4 |
| Eye infection | 0/85 (0%) | 0 | 2/85 (2.4%) | 2 |
| Gastrointestinal infection | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Infection | 1/85 (1.2%) | 1 | 2/85 (2.4%) | 2 |
| Lower respiratory tract infection | 2/85 (2.4%) | 2 | 7/85 (8.2%) | 7 |
| Lung infection | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Mastoiditis | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Otitis media | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Paronychia | 2/85 (2.4%) | 2 | 0/85 (0%) | 0 |
| Pharyngitis | 2/85 (2.4%) | 2 | 2/85 (2.4%) | 2 |
| Pneumonia | 3/85 (3.5%) | 3 | 1/85 (1.2%) | 1 |
| Prostate infection | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Respiratory tract infection | 19/85 (22.4%) | 19 | 31/85 (36.5%) | 31 |
| Root canal infection | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Sinusitis | 15/85 (17.6%) | 15 | 10/85 (11.8%) | 10 |
| Skin infection | 5/85 (5.9%) | 5 | 4/85 (4.7%) | 4 |
| Systemic infection | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Tonsillitis | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Tooth abscess | 1/85 (1.2%) | 1 | 2/85 (2.4%) | 2 |
| Tooth infection | 3/85 (3.5%) | 3 | 0/85 (0%) | 0 |
| Upper respiratory tract infection | 17/85 (20%) | 17 | 17/85 (20%) | 17 |
| Urinary tract infection | 9/85 (10.6%) | 9 | 7/85 (8.2%) | 7 |
| Herpes simplex | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Herpes zoster | 1/85 (1.2%) | 1 | 1/85 (1.2%) | 1 |
| Oral herpes | 0/85 (0%) | 0 | 2/85 (2.4%) | 2 |
| Respiratory tract infection viral | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Varicella zoster virus infection | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Viral infection | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Investigations | ||||
| Streptococcus test positive | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
| Skin and subcutaneous tissue disorders | ||||
| Eczema | 1/85 (1.2%) | 1 | 0/85 (0%) | 0 |
| Rosacea | 0/85 (0%) | 0 | 1/85 (1.2%) | 1 |
Limitations/Caveats
[Not Specified]
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Prof David Jayne |
|---|---|
| Organization | Cambridge University Hospitals NHS Foundation Trust |
| Phone | 01223 748062 |
| dj106@cam.ac.uk |
Responsible Party:
David Jayne,
Director, Vasculitis and Lupus Clinic,
Cambridge University Hospitals NHS Foundation Trust
ClinicalTrials.gov Identifier:
NCT01697267
Other Study ID Numbers:
- RITAZAREM
- 2012-001102-14
First Posted:
Oct 2, 2012
Last Update Posted:
Mar 18, 2022
Last Verified:
Feb 1, 2022