Ulcerative Colitis
Conditions
Keywords
Acute Severe Ulcerative Colitis, Steroid Refractory Ulcerative Colitis
Brief summary
The purpose of this study is to identify whether an Accelerated or Intensified Infliximab induction regimen is superior to Standard induction in Acute Severe Ulcerative Colitis in an open label multi-centre randomised controlled trial.
Interventions
DRUGInfliximab
INFLIXIMAB (REMICADE) in the form of a freeze-dried compound is conditioned in 100mg vials. Treatment will first be reconstituted in 250ml isotonic saline solution and infused
Sponsors
University of Melbourne
Austin Health
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Age \>18 years old * Diagnosis of Ulcerative Colitis * Acute Severe Colitis according to the Truelove and Witt's Criteria * Steroid refractory according to the Oxford Criteria
Exclusion criteria
* Participant unable to consent for themselves * Indication for immediate surgery (acute abdomen, perforation of the bowel, haemorrhage) * Crohn's disease * Participants with enteric infection confirmed on stool microscopy, culture or toxin * Haemodynamic instability (mean arterial pressure \<60) and not responsive to fluids * Participants with clinically significant Cytomegalovirus infection (positive inclusion bodies, immunohistochemistry and signs of viraemia such as fever and abnormal liver function tests) * Participants who are pregnant or currently breast-feeding * Participants with current malignancy, excluding basal cell carcinoma * Participants with flat low or high grade colonic dysplasia; sporadic adenomas permitted * Participants with serious co-morbidities including: Immunodeficiency; Myocardial infarction or acute stroke within the last 3 months; Moderate or severe heart failure (New York Heart Association class III or IV); Active or suspected tuberculosis; Renal failure; Hepatic failure; other severe infections * Participants with history of hypersensitivity to infliximab or infliximab biosimilar * Participants who have received other immunosuppressive agents including but not limited to: Anti-TNF therapies within 3 months of screening (Infliximab, Infliximab biosimilar, Golimumab, Etanercept, Certolizumab or Adalimumab); Anti-integrins (Vedolizumb, Etrolizumab) within 4 months of screening; Calcineurin inhibitors (Cyclosporine, Tacrolimus) within 4 weeks of screening; T or B cell depleters (Rituximab, Alemtuzumab) within 12 months of screening; other investigational agents (eg. Ustekinumab) within 6 months of screening
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Clinical response by day 7 | Day 7 | Defined as a reduction in the Lichtiger score below 10 with a decrease of at least 3 points and an improvement in rectal bleeding and stool frequency to ≤4 per day |
Secondary
| Measure | Time frame |
|---|---|
| Time to clinical response | Up to 3 months |
| Colectomy by Day 7 | From Day 0 to Day 7 |
Other
| Measure | Time frame | Description |
|---|---|---|
| Colectomy free survival at 1 month, 3 months and 12 months | Up to 12 months | Effect estimates between different dose regimens |
| Steroid free remission at 3 months | Day 90 | Defined as a Mayo disease activity index score ≤2 with an endoscopic subscore ≤1 |
| Endoscopic remission rates at 3 and 12 months | Up to 12 months | Defined by a Mayo endoscopic subscore of ≤1 |
Countries
Australia
Outcome results
None listed