TY - JOUR
T1 - Randomised controlled trial. Comparison of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis
T2 - Trial design and protocol (CONSTRUCT)
AU - Seagrove, Anne C.
AU - Alam, M. Fasihul
AU - Alrubaiy, Laith
AU - Cheung, Wai Yee
AU - Clement, Clare
AU - Cohen, David
AU - Grey, Michelle
AU - Hilton, Mike
AU - Hutchings, Hayley
AU - Morgan, Jayne
AU - Rapport, Frances
AU - Roberts, Stephen E.
AU - Russell, Daphne
AU - Russell, Ian
AU - Thomas, Linzi
AU - Thorne, Kymberley
AU - Watkins, Alan
AU - Williams, John G.
N1 - Copyright the Author(s) 2014. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.
PY - 2014/4/29
Y1 - 2014/4/29
N2 - Introduction: 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 and analysis: 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. Ethics and dissemination: 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. Trial registration number: ISRCTN: 22663589; EudraCT number: 2008-001968-36.
AB - Introduction: 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 and analysis: 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. Ethics and dissemination: 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. Trial registration number: ISRCTN: 22663589; EudraCT number: 2008-001968-36.
UR - http://www.scopus.com/inward/record.url?scp=84899736293&partnerID=8YFLogxK
U2 - 10.1136/bmjopen-2014-005091
DO - 10.1136/bmjopen-2014-005091
M3 - Article
C2 - 24785401
AN - SCOPUS:84899736293
SN - 2044-6055
VL - 4
SP - 1
EP - 11
JO - BMJ Open
JF - BMJ Open
IS - 4
M1 - e005091
ER -