Randomised controlled trial. Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: Trial design and protocol (CONSTRUCT).
BACKGROUND
Many patients with ulcerative colitis (UC) present with acute exacerbations needing hospital admission. Treatment includes intravenous steroids but up to 40% of patients do not respond and require emergency colectomy. Mortality following emergency colectomy has fallen, but 10% of patients still die within 3 months of surgery. Infliximab and ciclosporin, both immunosuppressive drugs, offer hope for treating steroid-resistant UC as there is evidence of their short-term effectiveness. As there is little long-term evidence, this pragmatic randomised trial, known as Comparison Of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: a Trial (CONSTRUCT), aims to compare the clinical and cost-effectiveness of infliximab and ciclosporin for steroid-resistant UC.


METHODS
Between May 2010 and February 2013, 52 UK centres recruited 270 patients admitted with acute severe UC who failed to respond to intravenous steroids but did not need surgery. We allocated them at random in equal proportions between infliximab and ciclosporin.The primary clinical outcome measure is quality-adjusted survival, that is survival weighted by Crohn's and Colitis Questionnaire (CCQ) participants' scores, analysed by Cox regression. Secondary outcome measures include: the CCQ-an extension of the validated but community-focused UK Inflammatory Bowel Disease Questionnaire (IBDQ) to include patients with acute severe colitis and stoma; two general quality of life measures-EQ-5D and SF-12; mortality; survival weighted by EQ-5D; emergency and planned colectomies; readmissions; incidence of adverse events including malignancies, serious infections and renal disorders; disease activity; National Health Service (NHS) costs and patient-borne costs. Interviews investigate participants' views on therapies for acute severe UC and healthcare professionals' views on the two drugs and their administration.


BACKGROUND
The Research Ethics Committee for Wales has given ethical approval (Ref. 08/MRE09/42); each participating Trust or Health Board has given NHS Reseach & Development approval. We plan to present trial findings at international and national conferences and publish in high-impact peer-reviewed journals.
22663589; EudraCT number: 2008-001968-36.
College of Medicine, Swansea University, Singleton Park, Swansea, UK.
Anne C
AC
Seagrove
M Fasihul
MF
Alam
Laith
L
Alrubaiy
Wai-Yee
WY
Cheung
Clare
C
Clement
David
D
Cohen
Michelle
M
Grey
Mike
M
Hilton
Hayley
H
Hutchings
Jayne
J
Morgan
Frances
F
Rapport
Stephen E
SE
Roberts
Daphne
D
Russell
Ian
I
Russell
Linzi
L
Thomas
Kymberley
K
Thorne
Alan
A
Watkins
John G
JG
Williams
D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D003082:Colectomy; D003093:Colitis, Ulcerative / Q000188:drug therapy* / Q000503:physiopathology / Q000601:surgery; D003362:Cost-Benefit Analysis; D016572:Cyclosporine / Q000191:economics / Q000627:therapeutic use*; D018450:Disease Progression; D016527:Drug Costs; D004351:Drug Resistance; D006801:Humans; D007166:Immunosuppressive Agents / Q000191:economics / Q000627:therapeutic use*; D000069285:Infliximab / Q000191:economics / Q000627:therapeutic use*; D011788:Quality of Life; D019057:Quality-Adjusted Life Years; D006113:United Kingdom
D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D000069285:Infliximab
Acute severe; Ciclosporin; Infliximab; Randomised controlled trial; Steroid refractory; Ulcerative colitis