Optimising Infliximab Induction Therapy for Acute Severe Ulcerative Colitis (PREDICT UC)

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

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.

Study Overview

• Status: Completed
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Infliximab

• Study Type: Interventional
• Enrollment (Actual): 138
• Phase: Phase 4

Contacts and Locations

Study Locations

• Australia
  • Victoria
    • Melbourne, Victoria, Australia, 3084
      • Austin Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Intensified Infliximab Induction; Infliximab 10mg/kg at Week 0 and Week 1	Drug: Infliximab; 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; Other Names: Remicade
Active Comparator: Accelerated Infliximab Induction; Infliximab 5mg/kg at Week 0, Week 1 and Week 3	Drug: Infliximab; 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; Other Names: Remicade
Active Comparator: Standard Infliximab Induction; Infliximab 5mg/kg at Week 0, Week 2 and Week 6	Drug: Infliximab; 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; Other Names: Remicade

What is the study measuring?

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	Time Frame
Time to clinical response	Up to 3 months
Colectomy by Day 7	From Day 0 to Day 7

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Colectomy free survival at 1 month, 3 months and 12 months	Effect estimates between different dose regimens	Up to 12 months
Steroid free remission at 3 months	Defined as a Mayo disease activity index score ≤2 with an endoscopic subscore ≤1	Day 90
Endoscopic remission rates at 3 and 12 months	Defined by a Mayo endoscopic subscore of ≤1	Up to 12 months

Collaborators and Investigators

• Sponsor: Austin Health
• Collaborators: University of Melbourne
• Investigators: Principal Investigator: Peter De Cruz, MBBS PhD FRACP, Austin Health, Melbourne; Principal Investigator: Matthew C Choy, MBBS BMedSci FRACP, Austin Health, Melbourne

Study record dates

Study Major Dates

• Study Start (Actual): July 18, 2016
• Primary Completion (Actual): October 1, 2021
• Study Completion (Actual): September 7, 2022

Study Registration Dates

• First Submitted: May 9, 2016
• First Submitted That Met QC Criteria: May 10, 2016
• First Posted (Estimated): May 12, 2016

Study Record Updates

• Last Update Posted (Actual): June 1, 2023
• Last Update Submitted That Met QC Criteria: May 30, 2023
• Last Verified: May 1, 2023

More Information

Terms related to this study

• Keywords: Acute Severe Ulcerative Colitis; Steroid Refractory Ulcerative Colitis
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Anti-Inflammatory Agents; Antirheumatic Agents; Gastrointestinal Agents; Dermatologic Agents; Tumor Necrosis Factor Inhibitors; Infliximab
• Other Study ID Numbers: HREC/14/Austin/595

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No