Ciclosporin and azathioprine treatment in severe ulcerative colitis: a double-blind controlled trial to evaluate short and long-term outcome

ISRCTN	ISRCTN56331683
DOI	https://doi.org/10.1186/ISRCTN56331683
Protocol serial number	N/A
Sponsor	University of Nottingham (UK)
Funder	Novartis Pharmaceuticals UK Ltd (UK) - unconditional block grant (ref: COLO400A 2423)

Submission date: 26/05/2005
Registration date: 20/07/2005
Last edited: 30/07/2014

Recruitment status: Stopped
Overall study status: Stopped
Condition category: Digestive System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Prof Christopher J Hawkey
Scientific

Wolfson Digestive Diseases Centre
University Hospital
Nottingham
NG7 2UH
United Kingdom

Phone	+44 (0)115 9709353
Email	cj.hawkey@nottingham.ac.uk

Study information

Primary study design	Interventional
Study design	Randomised double-blind placebo-controlled trial
Secondary study design	Randomised controlled trial
Scientific title
Study acronym	UC CAT
Study objectives	Does use of oral microemulsion ciclosporin, followed by azathioprine, in patients admitted to hospital with acute severe ulcerative colitis reduce the need for colectomy in the short term (at six months), and long term (two years)?
Ethics approval(s)	Not provided at time of registration
Health condition(s) or problem(s) studied	Severe ulcerative colitis
Intervention	Oral microemulsion of ciclosporin (5.5 to 6.5 mg/kg/day twice a day [bd]) or matched placebo. All patients continue to receive intravenous hydrocortisone and other standard medical therapy. At discharge, patients will start treatment with azathioprine (50 mg daily, increasing to 2 mg/kg after two weeks) and a tapering dose of prednisolone. Updated 30/07/2014: the trial was stopped due to poor recruitment.
Intervention type	Drug
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Ciclosporin, azathioprine, hydrocortisone, prednisolone
Primary outcome measure(s)	All Patients Treated disease status at six months, defined as: Treatment success = no colectomy and remission off steroid therapy Partial treatment success = symptoms of active disease, or treatment with steroids (oral or enema) Treatment failure = colectomy
Key secondary outcome measure(s)	1. Treatment outcome at two years (All Patients Treated disease status as defined for primary end-point above) 2. Treatment outcome at three months (All Patients Treated disease status as defined for primary outcome above) 3. Treatment response at 7 days (three or fewer non-bloody stools) 4. Time to remission and time to subsequent relapse measured by life table analysis 5. Quality of life at 6 months assessed using the McMaster inflammatory bowel disease questionnaire and EQ-5D scores 6. Overall incidence of adverse events 7. Employment status and amount of sick leave during follow-up 8. Patients valuation of outcome expressed in terms of time trade-off
Completion date	31/05/2011
Reason abandoned (if study stopped)	Participant recruitment issue

Eligibility

Participant type(s)	Patient
Age group	Adult
Sex	All
Target sample size at registration	280
Key inclusion criteria	Patients admitted to hospital with severe ulcerative colitis, who have been treated with intravenous corticosteroids for between 48 hours and 5 days, and still fulfil Truelove and Witts criteria for severe colitis.
Key exclusion criteria	1. Positive stool culture for enteric pathogens or Clostridium difficile 2. Cholesterol level below 3 mM 3. Greater than 5 days treatment with intravenous corticosteroids 4. Crohn's disease 5. Bowel perforation, or obstructive symptoms not due substantially to active inflammation 6. Pregnancy or lactation, or inability to take contraception during the trial 7. Treatment with ciclosporin tacrolimus or infliximab in the three months prior to study entry 8. Serious intercurrent infection or other active disease within three months prior to treatment 9. History of concurrent malignancy, or evidence of colonic dysplasia 10. Known human immunodeficiency virus (HIV) infection 11. Toxic dilation of the colon or clinical condition where colectomy is highly likely 12. Significant renal impairment (serum creatinine above 130 uM) 13. Uncontrolled hypertension
Date of first enrolment	01/06/2005
Date of final enrolment	31/05/2011

Locations

Countries of recruitment

United Kingdom
England

Study participating centre

Wolfson Digestive Diseases Centre

Nottingham
NG7 2UH
United Kingdom

Results and Publications

Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
IPD sharing plan