Clinical Trial: Rituximab in Active Ulcerative Colitis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase 3: Randomised Controlled Trial of Rituximab in Active Ulcerative Colitis

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 Summary:

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 300,000 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 [18,19] 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 Crohn's disease who also had immune-mediated thrombocytopaenia [20]. The thrombocytopaenia improved but the Crohn's disease did not. It can be argued though that there is little or no evidence for autoimmunity in Crohn's disease which seems in many cases to be due to a defect in phagocyte
Sponsor: Royal Liverpool University Hospital

Current Primary Outcome: Remission defined as a decrease in Mayo score to ≤ 2 points at week 4 [ Time Frame: week 4 ]

Original Primary Outcome: Remission defined as a decrease in Mayo score to ≤ 2 points at week 4

Current Secondary Outcome:

  • Clinical response defined as a decrease in Mayo score by ≥ 3 points at weeks 4, 8 (partial Mayo score) and 12. [ Time Frame: Week 4, 8 & 12 ]
  • Remission at weeks 8 and 12. [ Time Frame: week 8 &12 ]
  • Endoscopic mucosal healing at week 4 and 12 [ Time Frame: Week 4 & 12 ]
  • Improvement in Inflammatory Bowel Disease specific Quality of Life Index at weeks 4 and 12 [ Time Frame: weeks 4 &12 ]
  • Histological improvement of disease activity at 4 and 12 weeks compared with baseline. [ Time Frame: week 4 & 12 weeks ]
  • Treatment tolerability as defined by adverse events. [ Time Frame: all visits ]


Original Secondary Outcome:

  • Clinical response defined as a decrease in Mayo score by ≥ 3 points at weeks 4, 8 (partial Mayo score) and 12.
  • Remission at weeks 8 and 12.
  • Endoscopic mucosal healing at week 4 and 12
  • Improvement in Inflammatory Bowel Disease specific Quality of Life Index [22] [Appendix 2] at weeks 4 and 12
  • Histological improvement of disease activity at 4 and 12 weeks compared with baseline. Scored as follows:
  • 0 = no polymorphs
  • 1 = small numbers of polymorphs in the lamina propria with minimal infiltration of crypts
  • 2 = prominent polymorphs in the lamina propria with infiltration of ³ 50% of crypts
  • 3 = florid polymorph infiltrate with crypt abscesses
  • 4 = florid acute inflammation with ulceration
  • Treatment tolerability as defined by adverse events.


Information By: Royal Liverpool University Hospital

Dates:
Date Received: November 29, 2005
Date Started: April 2004
Date Completion:
Last Updated: November 5, 2014
Last Verified: November 2014