Optimising Infliximab Induction Therapy for Acute Severe Ulcerative Colitis

Study Overview
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Brief Summary
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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.

Official Title
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PREDICT UC: Optimising Infliximab Induction Therapy for Acute Severe Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: Infliximab


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 80 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Intensified Infliximab Induction<br>Infliximab 10mg/kg at Week 0 and Week 1 | Drug: Infliximab<br>* 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<br>* Other names: Remicade;|
| Active Comparator: Accelerated Infliximab Induction<br>Infliximab 5mg/kg at Week 0, Week 1 and Week 3 | Drug: Infliximab<br>* 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<br>* Other names: Remicade;|
| Active Comparator: Standard Infliximab Induction<br>Infliximab 5mg/kg at Week 0, Week 2 and Week 6 | Drug: Infliximab<br>* 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<br>* Other names: Remicade;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical response by 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 | Day 7 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Time to clinical response |  | Up to 3 months | 
| Colectomy by Day 7 |  | From Day 0 to Day 7 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acute Severe Ulcerative Colitis, Steroid Refractory Ulcerative Colitis