Details of HTA project in progress
Last updated: 31 August 2010 - Next update due: 7 September 2010
Research type: |
Primary Research (e.g. trial) |
Project title: |
COmparison of iNfliximab and ciclosporin in STeroid Resistant Ulcerative Colitis: a Trial (CONSTRUCT) |
Project ref: |
06/78/03 |
Cost: |
£1,693,111 |
Chief Investigator : |
Professor John G Williams, Prof Health Srvcs Rsrch/Consult Gastroenterologist, School of Medicine, Swansea University |
Start Date: |
September 2008 |
Estimated date of publication in HTA journal series: |
Late 2013. This date takes account of time for report preparation and printing based on current average times for these activities. |
Plain English Summary |
Ulcerative colitis (UC) is a chronic debilitating disease that affects approximately 150,000 people in the UK, and is one of the most important diseases seen by gastroenterologists. It often leads to severe morbidity, grossly impaired quality of life, frequent and long inpatients stays and emergency colectomy, and is therefore a major burden on patients and NHS resources. Recent studies have reported that two new drugs, infliximab and ciclosporin, are often effective in treating steroid resistant UC in the short term,[2,3] but there is a lack of evidence in the longer-term.[4] Rigorous longer term investigation of the clinical and cost effectiveness is now required for both infliximab and ciclosporin. The HTA call and this project proposal have been designed to fill this important gap in the evidence. The proposed project will use a two arm trial to compare the clinical and cost effectiveness of infliximab and ciclosporin in 40 centres in the UK. Using intensive follow-up for two years and routine records for a further eight, the study will assess QoL, death rates, colectomy, severe illness, NHS and patient borne costs, and patient views for these treatments. The applicants are ideally suited to this project since they have an international reputation in designing and leading major RCTs in gastroenterology and UC. This includes the MINuET study, led by John Williams and Ian Russell that compared the clinical and cost effectiveness of nurses and doctors performing endoscopies across 29 UK centres and 1900 patients. The applicants also have clinical expertise in UC, expertise in health economics, health services research, design and co-ordination of multicentre randomised trials, public health, epidemiology and various research methods. John Williams has led two major studies for the HTA programme and is currently directing projects to improve the quality and use of routine data in England and Wales, through the Royal College of Physicians' Information Laboratory and HIRU at Swansea University. These developments will enable us to extend the follow-up period to 10 years with no financial costs for the commissioners. David Cohen, who directs the Health Economics and Policy Research Unit at Glamorgan University, will lead the health economics component of the trial. Ian Russell, who directs the North Wales Organisation of Randomised Trials in Health (NWORTH), will be lead trial methodologist and mentor. |
Project Abstract: |
Ulcerative colitis (UC) is a chronic disease with many unanswered questions regarding causes, course, treatment and outcome. It can present as an acute severe illness, requiring intravenous steroids but some patients are steroid resistant. In the past, emergency surgery to remove the colon was then the only option. Infliximab and ciclosporin are drugs that offer hope for treating steroid resistant UC. There is evidence that they are effective in the short term but evidence about their clinical effectiveness and cost effectiveness is lacking. The overall aim of this study is to compare the clinical effectiveness and cost effectiveness of these drugs in this situation and a key objective is to establish long-term data collection to enable answers to further research questions regarding progress and outcome following treatment with steroids, infliximab, ciclosporin or surgery. This study, funded by NIHR Health Technology Assessment programme, is a pragmatic randomised controlled trial (RCT) involving 40 UK centres. Inpatients with acute severe UC who fail to respond to intravenous steroids but do not require immediate surgery, will be randomised to either infliximab or ciclosporin (480 patients). The primary outcome measure will be Quality of Life. Secondary outcomes measures will be emergency and planned colectomy, additional medical therapy, mortality, quality adjusted survival, disease activity, readmissions, length of remission, incidence of malignancies, incidence of serious infections, incidence of renal disorders, incidence of new symptoms, total NHS costs and patient borne costs. Patient interviews will be undertaken to investigate the views of patients regarding therapies for acute severe UC. Study data will be collected using a web-based clinical information system and record linkage of electronically held routine data. Research data collection will continue for two years; clinical data collection and record linkage will then continue for the following eight years. |
ISRCTN* number: | ISRCTN 22663589 (*International Standard Randomised Controlled Trial Number) URL of this project on the Controlled Trials Website: http://www.controlled-trials.com/ISRCTN22663589 |
Project Protocol: |
Project protocol (pdf format, 435 kbytes) |
URL of this page: |
http://www.hta.ac.uk/1737 |
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