Ignite Creation Date:
2024-05-05 @ 12:11 PM
Last Modification Date:
2024-10-26 @ 9:21 AM
Study NCT ID:
NCT00261118
Status:
COMPLETED
Last Update Posted:
2014-11-06
First Post:
2005-11-29
Brief Title:
Rituximab in Active Ulcerative Colitis
Sponsor:
Royal Liverpool University Hospital
Organization:
Royal Liverpool University Hospital
Study Overview
Official Title:
Phase 3 Randomised Controlled Trial of Rituximab in Active Ulcerative Colitis
Status:
COMPLETED
Status Verified Date:
2014-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
There is broad support for the hypothesis that Ulcerative colitis is an auto-immune disease Rituximab is an antibody protein that removes a subgroup of white blood cells B lymphocytes from the circulation These cells have the capacity to generate the auto-antibodies that typify auto-immune disease Although Rituximab has been mainly used for treating B lymphocyte malignancies lymphoma it has also been used with promising results in Rheumatoid arthritis and has an excellent safety record This is a small placebo-controlled trial to assess its efficacy and safety in patients with steroid-resistant active ulcerative colitis
Detailed Description:
WHAT IS THE PROBLEM TO BE ADDRESSED
Lack of effective cure for Ulcerative colitis
WHAT IS THE HYPOTHESIS TO BE TESTED
That rituximab may be effective in active ulcerative colitis
WHY IS A TRIAL NEEDED NOW
Rituximab has been used to treat more than 300000 patients with B lymphocyte malignancies and has been shown to have an excellent safety record 6-8 Published pilot studies have shown excellent results with rituximab in patients with autoimmune diseases such as immune-mediated thrombocytopaenia Wegeners granulomatosis cold agglutinin disease myasthenia gravis rheumatoid arthritis and SLE 11-17 Together with increasing evidence to support a pathogenic role for the pANCA associated with ulcerative colitis a study of rituximab in ulcerative colitis is timely Moreover the only significant advance in the treatment of ulcerative colitis in recent years has been the introduction of cyclosporin which probably halves the colectomy rate 1819 but at the risk of considerable side effects and with a drug-related mortality that has been estimated at 2
HAS A SYSTEMATIC REVIEW BEEN CARRIED OUT AND WHAT WERE THE FINDINGS
A Medline search for rituximab and ulcerative colitis yielded no responses There has been a recent report of its use in a single patient with ileocolonic Crohns disease who also had immune-mediated thrombocytopaenia 20 The thrombocytopaenia improved but the Crohns disease did not It can be argued though that there is little or no evidence for autoimmunity in Crohns disease which seems in many cases to be due to a defect in phagocyte function eg in association with the recently described NOD2CARD15 genetic alteration
25 HOW WILL THE RESULTS OF THIS TRIAL BE USED This trial will establish whether rituximab is effective in achieving remission in patients with ulcerative colitis who are failing to respond to conventional therapy with corticosteroids Because there is no background evidence of its efficacy the initial study will be a small two centre study with placebo blinding If the result of this study is promising these would be used as pilot data for power calculations for a larger multicentre study
31 WHAT IS THE PROPOSED TRIAL DESIGN A placebo-blinded study with 16 patients receiving rituximab and 6 patients receiving placebo 09 saline
32 WHAT ARE THE PLANNED TRIAL INTERVENTIONS Patients will receive either i rituximab 1g in 500 mls of 09 saline infused into a peripheral vein over four hours see appended infusion chart or ii 500 mls of 09 saline infused into a peripheral vein over two hours as placebo This regimen will be repeated once at 2 weeks This protocol is based on the dosing regimen that proved most efficacious for rheumatoid arthritis All patients will also receive paracetamol 1g orally and chlorpheniramine Piriton 10mg intravenously immediately prior to each Rituximabplacebo infusion
All patients will continue to receive oral prednisolone 40mgday for 2 weeks then 30mg for two weeks then 20mgsday for two weeks then reduce by 5mgday every 7 days until off prednisolone
33 WHAT IS THE PROPOSED DURATION OF THE TREATMENT PERIOD Two treatments two weeks apart
34 WHAT ARE THE PROPOSED INCLUSIONEXCLUSION CRITERIA see earlier
35 WHAT ARE THE PROPOSED OUTCOME MEASURES see earlier 36 WILL HEALTH SERVICE RESEARCH ISSUES BE ADDRESSED Not Applicable 37 WHAT IS THE PROPOSED FREQUENCYDURATION OF FOLLOW UP Patients will be reviewed after one two and four eight twelve and twenty four weeks Patients will be monitored thereafter in routine gastroenterology clinic follow up
38 HOW WILL THE OUTCOME MEASURES BE MEASURED AT FOLLOW-UP Patients will complete a daily diary with details of bowel frequency presence of blood in the stool any change in medical therapy and any new or worsening symptoms The IBD quality of life questionnaire will be completed at baseline and at weeks 4 and 12
Patients will also have a diary card to record the details of any other symptoms noted during the trial to assess adverse effects of the trial treatment
39 WHAT ARE THE PROPOSED PRACTICAL ARRANGEMENTS FOR ALLOCATING PATIENTS TO TRIAL GROUPS Randomization will be allocated in blocks of five by the pharmacy department of the hospital
310 WHAT ARE THE PROPOSED METHODS FOR PROTECTING AGAINST OTHER SOURCES OF BIAS Controls known only to the Pharmacy Department will receive a placebo saline infusion
311 WHAT IS THE PROPOSED SAMPLE SIZE A placebo-blinded study with 16 patients receiving rituximab and 8 patients receiving placebo 09 saline This will provide 80 power for excluding an 80 remission rate with active treatment compared with an assumed 25 placebo response
312 WHAT IS THE PLANNED RECRUITMENT RATE 1-2 patients per month 313 ARE THERE LIKELY TO BE ANY PROBLEMS WITH COMPLIANCE No
314 WHAT IS THE LIKELY RATE OF LOSS TO FOLLOW UP 100 follow up should be achievable 315 HOW MANY CENTRES WILL BE INVOLVED Two 316 WHAT IS THE PROPOSED TYPE OF ANALYSIS Formal hypothesis testing of the primary outcome will be compared by chi-square test
Wilcoxon signed rank test will be used for comparisons against baseline for changes in secondary quantitative endpoints
317 WHAT IS THE PROPOSED FREQUENCY OF ANALYSIS Once only on completion 318 ARE THERE ANY PLANNED SUBGROUP ANALYSES Subgroup analysis may be performed according to pANCA status
319 WHAT IS THE ESTIMATED RESEARCH COST OF THE TRIAL Cost of therapy plus 800 pharmacy fee plus 2200 towards ethics submission research nurse time cost of pANCA assays to be provided as an unrestricted educational grant from Roche UK
320 IS THERE AN NHS SERVICE SUPPORT COST OF THIS TRIAL AND IF SO WHAT IS THE ESTIMATED COST The only NHS cost would be modest involving only the routine testing of full blood count and SMAC which is current practice in the monitoring of patients with relapses of inflammatory bowel disease
Lack of effective cure for Ulcerative colitis
WHAT IS THE HYPOTHESIS TO BE TESTED
That rituximab may be effective in active ulcerative colitis
WHY IS A TRIAL NEEDED NOW
Rituximab has been used to treat more than 300000 patients with B lymphocyte malignancies and has been shown to have an excellent safety record 6-8 Published pilot studies have shown excellent results with rituximab in patients with autoimmune diseases such as immune-mediated thrombocytopaenia Wegeners granulomatosis cold agglutinin disease myasthenia gravis rheumatoid arthritis and SLE 11-17 Together with increasing evidence to support a pathogenic role for the pANCA associated with ulcerative colitis a study of rituximab in ulcerative colitis is timely Moreover the only significant advance in the treatment of ulcerative colitis in recent years has been the introduction of cyclosporin which probably halves the colectomy rate 1819 but at the risk of considerable side effects and with a drug-related mortality that has been estimated at 2
HAS A SYSTEMATIC REVIEW BEEN CARRIED OUT AND WHAT WERE THE FINDINGS
A Medline search for rituximab and ulcerative colitis yielded no responses There has been a recent report of its use in a single patient with ileocolonic Crohns disease who also had immune-mediated thrombocytopaenia 20 The thrombocytopaenia improved but the Crohns disease did not It can be argued though that there is little or no evidence for autoimmunity in Crohns disease which seems in many cases to be due to a defect in phagocyte function eg in association with the recently described NOD2CARD15 genetic alteration
25 HOW WILL THE RESULTS OF THIS TRIAL BE USED This trial will establish whether rituximab is effective in achieving remission in patients with ulcerative colitis who are failing to respond to conventional therapy with corticosteroids Because there is no background evidence of its efficacy the initial study will be a small two centre study with placebo blinding If the result of this study is promising these would be used as pilot data for power calculations for a larger multicentre study
31 WHAT IS THE PROPOSED TRIAL DESIGN A placebo-blinded study with 16 patients receiving rituximab and 6 patients receiving placebo 09 saline
32 WHAT ARE THE PLANNED TRIAL INTERVENTIONS Patients will receive either i rituximab 1g in 500 mls of 09 saline infused into a peripheral vein over four hours see appended infusion chart or ii 500 mls of 09 saline infused into a peripheral vein over two hours as placebo This regimen will be repeated once at 2 weeks This protocol is based on the dosing regimen that proved most efficacious for rheumatoid arthritis All patients will also receive paracetamol 1g orally and chlorpheniramine Piriton 10mg intravenously immediately prior to each Rituximabplacebo infusion
All patients will continue to receive oral prednisolone 40mgday for 2 weeks then 30mg for two weeks then 20mgsday for two weeks then reduce by 5mgday every 7 days until off prednisolone
33 WHAT IS THE PROPOSED DURATION OF THE TREATMENT PERIOD Two treatments two weeks apart
34 WHAT ARE THE PROPOSED INCLUSIONEXCLUSION CRITERIA see earlier
35 WHAT ARE THE PROPOSED OUTCOME MEASURES see earlier 36 WILL HEALTH SERVICE RESEARCH ISSUES BE ADDRESSED Not Applicable 37 WHAT IS THE PROPOSED FREQUENCYDURATION OF FOLLOW UP Patients will be reviewed after one two and four eight twelve and twenty four weeks Patients will be monitored thereafter in routine gastroenterology clinic follow up
38 HOW WILL THE OUTCOME MEASURES BE MEASURED AT FOLLOW-UP Patients will complete a daily diary with details of bowel frequency presence of blood in the stool any change in medical therapy and any new or worsening symptoms The IBD quality of life questionnaire will be completed at baseline and at weeks 4 and 12
Patients will also have a diary card to record the details of any other symptoms noted during the trial to assess adverse effects of the trial treatment
39 WHAT ARE THE PROPOSED PRACTICAL ARRANGEMENTS FOR ALLOCATING PATIENTS TO TRIAL GROUPS Randomization will be allocated in blocks of five by the pharmacy department of the hospital
310 WHAT ARE THE PROPOSED METHODS FOR PROTECTING AGAINST OTHER SOURCES OF BIAS Controls known only to the Pharmacy Department will receive a placebo saline infusion
311 WHAT IS THE PROPOSED SAMPLE SIZE A placebo-blinded study with 16 patients receiving rituximab and 8 patients receiving placebo 09 saline This will provide 80 power for excluding an 80 remission rate with active treatment compared with an assumed 25 placebo response
312 WHAT IS THE PLANNED RECRUITMENT RATE 1-2 patients per month 313 ARE THERE LIKELY TO BE ANY PROBLEMS WITH COMPLIANCE No
314 WHAT IS THE LIKELY RATE OF LOSS TO FOLLOW UP 100 follow up should be achievable 315 HOW MANY CENTRES WILL BE INVOLVED Two 316 WHAT IS THE PROPOSED TYPE OF ANALYSIS Formal hypothesis testing of the primary outcome will be compared by chi-square test
Wilcoxon signed rank test will be used for comparisons against baseline for changes in secondary quantitative endpoints
317 WHAT IS THE PROPOSED FREQUENCY OF ANALYSIS Once only on completion 318 ARE THERE ANY PLANNED SUBGROUP ANALYSES Subgroup analysis may be performed according to pANCA status
319 WHAT IS THE ESTIMATED RESEARCH COST OF THE TRIAL Cost of therapy plus 800 pharmacy fee plus 2200 towards ethics submission research nurse time cost of pANCA assays to be provided as an unrestricted educational grant from Roche UK
320 IS THERE AN NHS SERVICE SUPPORT COST OF THIS TRIAL AND IF SO WHAT IS THE ESTIMATED COST The only NHS cost would be modest involving only the routine testing of full blood count and SMAC which is current practice in the monitoring of patients with relapses of inflammatory bowel disease
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None
Secondary IDs
| Secondary ID | Type | Domain | Link |
|---|---|---|---|
| MF 800012794 | None | None | None |
| DDX exemption from MRHA ref- | None | None | None |