Phase 3: Randomised Controlled Trial of Rituximab in Active Ulcerative Colitis
Trial Snapshot
- Phase
- Phase 2
- Status
- Completed
- Enrollment
- 24
- Locations
- 1
- Primary Endpoint
- Remission defined as a decrease in Mayo score to ≤ 2 points at week 4
Study Overview
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?
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Double (Participant, Investigator)
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- •Patients over age of 18 years who are capable of providing written informed consent.
- •Confirmed diagnosis of ulcerative colitis by conventional clinical, endoscopic and histological criteria.
- •Failure of response to at least two weeks of oral prednisolone 40mg/day.
- •Active colitis as assessed by a Mayo score [21] of 6-12 inclusive (see Appendix 1)
Exclusion Criteria
- •Patients under 18 or unable to give informed consent.
- •Patients in their first attack of ulcerative colitis.
- •Patients with severe ulcerative colitis as defined by presence of any of: temperature >37.5oC, pulse rate >100, focal severe or rebound abdominal tenderness, haemoglobin < 10.0g/dl, serum albumin <3.5 g/dl, transverse colon diameter greater than 5.0cms on plain abdominal X ray.
- •Patients who are pregnant, post partum (<3months) or breast feeding
- •Patients who are at risk of pregnancy and not using a reliable form of contraception (oral contraceptive and barrier or barrier plus spermicide).
- •Patients with a stoma
- •Positive stool culture for pathogens or test for C difficile at screening within 7 days prior to trial entry
- •Patients for whom a baseline Mayo score can not be reliably calculated: frequent use of laxatives (for proximal constipation) or antimotility agents (for control of diarrhoea)
- •Any change to maintenance medication for ulcerative colitis: azathioprine or 6-mercaptopurine within previous 3 months or 5-aminosalicylates within previous one month
- •Any change to rectal therapy for colitis within the previous two weeks.
- •Participation in other trials in the last 3 months.
- •Serious intercurrent infection or other clinically important active disease (including renal and hepatic disease)
Arms & Interventions
1 (i)
Rituximab 1g in 500 mls of 0.9% normal saline infused into a peripheral vein
Intervention: Rituximab (Drug)
2 (ii)
500 mls of 0.9% NORMAL SALINE INFUSED INTO A PERIPHERAL VEIN
Intervention: Rituximab (Drug)
Outcomes
Primary Outcomes
Remission defined as a decrease in Mayo score to ≤ 2 points at week 4
Time Frame: week 4
Secondary Outcomes
- Remission at weeks 8 and 12.(week 8 &12)
- Endoscopic mucosal healing at week 4 and 12(Week 4 & 12)
- Treatment tolerability as defined by adverse events.(all visits)
- Clinical response defined as a decrease in Mayo score by ≥ 3 points at weeks 4, 8 (partial Mayo score) and 12.(Week 4, 8 & 12)
- Histological improvement of disease activity at 4 and 12 weeks compared with baseline.(week 4 & 12 weeks)
- Improvement in Inflammatory Bowel Disease specific Quality of Life Index at weeks 4 and 12(weeks 4 &12)
Investigators
Jonathan Michael Rhodes
Invesitgator
Royal Liverpool University Hospital