Acute severe steroid resistant ulcerative colitis Digestive System Ulcerative colitis
Conditions
Interventions
Current interventions as of 22/10/2012:
Infliximab:
Infliximab as 5mg/kg intravenous infusion over a 2 hour period, at baseline and at 2 and 6 weeks after the first inf
Sponsors
Swansea University (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Current inclusion criteria as of 22/10/2012: 1.1. Patients admitted acutely (ie an emergency admission) with severe colitis (as evidenced by eg a Mayo score of at least 2 on endoscopic finding) who fail to respond to approximately 2-5 days of intravenous hydrocortisone therapy, who also have either: 1.2. A histological diagnosis of ulcerative colitis in this episode OR 1.3. A histological diagnosis of indeterminate colitis in this episode, where clinical judgement (based on macroscopic appearance, disease distribution or previous history) suggests a diagnosis of ulcerative colitis rather than Crohn?s disease OR 1.4. Typical symptoms of ulcerative colitis but histology awaited OR 1.5. A history of ulcerative colitis (previously confirmed histologically) Previous inclusion criteria until 22/10/2012: 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
Exclusion criteria
Exclusion criteria: Current exclusion criteria as of 22/10/2012: 1. Patient aged under 18 years of age on admission 2. Patient with histological diagnosis inconsistent with ulcerative colitis (indeterminate colitis is not necessarily ?inconsistent with ulcerative?-see inclusion criteria b) 3. Patient with enteric infection confirmed on stool microscopy or culture or histology (includes salmonella, shigella, clostridium difficile, campylobacter and CMV) 4. Patient from a vulnerable group 5. Patient unable to consent for themselves 6. Patient who are pregnant (as evidenced by +ve pregnancy test) or currently lactating 7. Women of child-bearing potential who are not prepared to use adequate contraception during treatment with infliximab and for 6 months afterwards in line with the Summary of Product Characteristics 8. Patient with current malignancy, excluding basal cell carcinoma 9. Patient with serious co-morbidities, including: 9.1. Immunodeficiency 9.2. Myocardial infarction (within last month) 9.3. Moderate or severe heart failure (NYHA class III or IV) 9.4. Acute stroke (within last month) 9.5. Respiratory failure 9.6. Renal failure 9.7. Hepatic failure 9.8. Active, or suspected active tuberculosis 9.9. Other severe infections (as determined by the investigator) such as sepsis, abscesses and opportunistic infections 10.1. Patient with a history of hypersensitivity to 10.2. Infliximab (Remicade) 10.3. Ciclosporin (Sandimmun and Neoral) 10.4. Polyethoxylated oils (Sandimmun Concentrate for IV Infusion) 11. Concomitant use of tacrolimus or rosuvastatin 12. Patients who do not speak English well enough to take part in the study, and for whom local translation services cannot be provided 13. Where clinical need determines the patient should undergo emergency colectomy without further medical treatment 14. Patients currently taking part in other clinical trials 15. Patients who have received treatment with either infliximab or ciclosporin in the three months before admission 16. Patient with contraindication(s) to treatment with Infliximab or Ciclosporin Previous exclusion criteria until 22/10/2012: 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Current primary outcome measures as of 22/10/2012: The primary outcome measure is quality-adjusted survival, weighted by scores on the disease-specific CCQ. Previous primary outcome measures until 22/10/2012: 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
| Measure | Time frame |
|---|---|
| Current secondary outcome measures as of 22/10/2012: 1. Generic SF-12 and EQ-5D QoL questionnaires. 2. Emergency and planned colectomy; centres report all colectomies undertaken based on clinical judgement and patient agreement, both emergency and elective. 3. Mortality. 4. Re-admissions, including those for non-UC-specific causes. 5. Incidence of malignancies, subdivided between colorectal, other GI and other malignancies. 6. Incidence of serious infections during treatment, including bacterial infections, pneumonia, abscesses, and other serious infections. 7. Incidence of renal disorders during treatment. 8. Incidence of new symptoms during or attributable to treatment. 9. Incidence of adverse events, grouped as SUSARs, SARs, SAEs, ARs or AEs and including all relevant events described in 3. to 8. above. 10. Disease activity, measured by the criteria proposed by Truelove and Witts: to this end we seek to measure full blood count, inflammatory markers and albumin at baseline and three, six, 12, 18, 24, 30 and 36 months. 11. Quality of life, measured by the CCQ. 12. NHS costs, measured by a healthcare resource use questionnaire and hospital activity data; the economic analysis will combine these with quality adjusted survival. 13. Patient borne costs, including number of days off work and travel costs to healthcare; we shall report these separately from NHS costs because the main economic analysis takes the perspective of the NHS. 14. Patient views, of the alternative drugs elicited through 12 (10%) telephone interviews in each arm following discharge from hospital about three months and 12 months after randomisation. 15. Healthcare professional views about the drugs and their administration; a minimum of 8 clinicians and 4 nurses | — |
Countries
United Kingdom, Wales
Outcome results
None listed