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| [ Print-friendly version ] |
| Comparison of infliximab and ciclosporin in steroid resistant ulcerative colitis: a trial |
| ISRCTN | ISRCTN22663589 |
| ClinicalTrials.gov identifier | |
| Public title | Comparison of infliximab and ciclosporin in steroid resistant ulcerative colitis: a trial |
| Scientific title | |
| Acronym | CONSTRUCT |
| Serial number at source | HTA 06/78/03; NRES: 08/MRE09/42 |
| Study hypothesis |
To determine the clinical and cost effectiveness of infliximab and ciclosporin in acute severe steroid resistant ulcerative colitis.
More details can be found at: http://www.nres.npsa.nhs.uk/researchsummaries/?entryid29=19437&q=0%c2%ac08%2fMRE09%2f42%c2%ac |
| Ethics approval | To be submitted to multi-centre research ethics committee (MREC) for Wales, Cardiff in May 2008. |
| Study design | Two-arm, pragmatic, multi-centre, randomised controlled trial. |
| Countries of recruitment | United Kingdom |
| Disease/condition/study domain | Acute severe steroid resistant ulcerative colitis |
| Participants - inclusion criteria |
1. Patients with ulcerative colitis (UC) diagnosed on histological evidence
2. Inpatients with documented evidence of acute severe UC (based on sigmoidoscopic appearances and Truelove and Witts' criteria) 3. Continuing acute severe UC (according to Truelove and Witts criteria) after three days intravenous hydrocortisone |
| Participants - exclusion criteria |
1. Age under 18 years on the day of admission
2. Treatment with either infliximab or ciclosporin in the three months before admission 3. Positive stool microscopy or culture for enteric infection, including salmonella, shigella and Clostridium difficile 4. Pregnancy and lactation 5. Malignancy, excluding basal cell carcinoma 6. Other serious co-morbidities, including immunodeficiency, myocardial infarction, acute stroke, respiratory, renal or hepatic failure 7. Severe cognitive impairment 8. Patients unable to consent for themselves 9. Patients who do not speak English well enough to take part in the study 10. Where clinical need determines the patient should undergo emergency colectomy without further medical treatment 11. Patients currently taking part in other clinical trials 12. Patients from vulnerable groups with the exception of severe illness as this will be the reason for their acute admission and treatment |
| Anticipated start date | 01/09/2008 |
| Anticipated end date | 31/08/2012 |
| Status of trial | Ongoing |
| Patient information material | Not available in web format, please use the contact details below to request a patient information sheet. |
| Target number of participants | 480 (240 in each arm) |
| Interventions |
Patients will be randomised to either infliximab (Remicade®) or ciclosporin (Sandimmun®/ Neoral®).
Both infliximab and ciclosporin will be used in accordance with normal routes of administration, dosage, dosage regimen and treatment periods as detailed below. Relapse or failure to respond at any stage will prompt surgical referral. Infliximab: Infliximab (5 mg per kg as a single intravenous infusion) at time 0 and further doses at 2 and 6 weeks followed by infusions every 8 weeks up to 6 months. The addition/continuation of azathioprine or 6-mercaptopurine is necessary if tolerated (to reduce likelihood of antibody formation). Steroids will be tapered over a 3 month period. Ciclosporin: Intravenous ciclosporin (2 mg per kg) for 7 days (aiming for trough levels of 150-250 ng/ml) will be followed by oral ciclosporin (8 mg/kg) for 3 months while the effect of either azathioprine or 6-mercaptopurine is allowed (commenced on discharge). During that 3 month period, steroids are also tapered and Septrin® should be given to cover for pneumocystis carinii pneumonia. Contact details of Principal Investigator: Prof John G Williams School of Medicine Swansea University Singleton Park, Swansea SA2 8PP, United Kingdom Tel: +44 (0)1792 513401 Email: j.g.williams@swansea.ac.uk |
| Primary outcome measure(s) |
Quality of life, measured at 3, 6, 12 and 24 months with the following:
1. Disease specific questionnaire: UK-Inflammatory Bowel Disease Questionnaire (IBDQ) 2. Generic questionnaires: The 12-item short form health survey (SF-12) and EQ-5D |
| Secondary outcome measure(s) |
1. Emergency and planned colectomy; colectomy may be undertaken based on clinical judgement and patient agreement. The incidence of emergency colectomy will be measured up to 2 years post-admission during the research data collection and up to 10 years during the clinical data collection and record linkage phase. Similarly, elective colectomy will be measured separately up to 2 years and 10 years follow-up.
2. Concomitant medical therapy; continuing steroid treatment, and/or the addition of azathioprine (or other immunosuppressive therapy) will be at the discretion of the attending team. Oral ciclosporin, or a second infusion of infliximab may be given. Data on treatment will be recorded by the patient after discharge up to 3 months after entry to the trial, and recorded at each hospital visit. 3. Mortality; which will be measured by case fatality and standardised mortality ratios up to 2 and 10 years follow-up. 4. Quality adjusted survival; to combine the effects of quality of life and mortality, will be measured up to 2 years follow-up and then modelled for lifetime Quality Adjusted Life Years 5. Disease activity; Full blood count, inflammatory markers and albumin will be measured at baseline and at 3, 6, 12 and 24 months. 6. Re-admissions; including for non-UC specific causes. Data will be collected for two years but monitored using routine data for a further eight years. 7. Total NHS costs; measured up to 2 years follow-up. 8. Patient borne costs; including number of days off work per year and travel costs for health care, up to 2 years follow-up. These will be reported separately from the NHS costs and will not be included in the cost utility estimates. 9. Patient views; elicited through telephone interviews, following discharge from hospital at approximately 2 to 3 and 6 to 8 months into follow-up. These will be conducted for 24 patients, 12 (5%) in each of the two trial arms. |
| Sources of funding | NIHR Health Technology Assessment Programme - HTA (UK) |
| Trial website | |
| Publications | |
| Contact name | Mrs Anne Seagrove |
| Address |
School of Medicine
Swansea University Singleton Park |
| City/town | Swansea |
| Zip/Postcode | SA2 8PP |
| Country | United Kingdom |
| Tel | +44 (0)1792 513411 |
| Fax | +44 (0)1792 513423 |
| a.c.seagrove@swansea.ac.uk | |
| Sponsor | Swansea University (UK) |
| Address | Singleton Park |
| City/town | Swansea |
| Zip/Postcode | SA2 8PP |
| Country | United Kingdom |
| Tel | +44 (0)1792 285412 |
| c.d.jones@swansea.ac.uk | |
| Sponsor website: | http://www.swan.ac.uk |
| Date applied | 15/05/2008 |
| Last edited | 11/03/2009 |
| Date ISRCTN assigned | 16/05/2008 |
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| © 2010 ISRCTN unless otherwise stated. | |
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