Comparison of medical RESCUE strategies for patients with steroid-refractory acute severe Ulcerative Colitis: an open-label randomized controlled trial
PI: Dr. Neeraj Narula, McMaster University
Co-Investigators
Dr. Vipul Jairath and Dr. Reena Khanna, Western University
Dr. Jeffrey McCurdy and Dr. Sanjay Murthy, University of Ottawa
Dr. Talat Bessissow and Dr. Waqqas Afif, McGill University
Dr. Robert Battat, University of Montreal
Dr. Remo Panaccione, Dr. Christopher Ma, and Dr. Cathy Lu, University of Calgary
Dr. Harminder Singh and Dr. Charles Bernstein, University of Manitoba
Dr. Farhad Peerani, University of Alberta
Dr. Laura Targownik, Dr. Zane Gallinger, and Dr. Parul Tandon, University of Toronto
Dr. Sunny Singh, University of British Colombia
Purpose
This study aims to examine patients with acute severe UC who are refractory to intravenous corticosteroids and determine whether a strategy of using upadacitinib first followed by infliximab in upadacitinib non-responders is non-inferior to conventional management with infliximab only.
Study Design
In this open-label pragmatic multi-centre RCT, ASUC patients (defined as Modified Truelove Witts Severity Index (MTWSI) > 10 with a Mayo endoscopic subscore >= 2) who are refractory to three days of intravenous steroids would be eligible for randomization (refractory is defined using the Oxford criteria of at day 3 of steroid therapy, presence of > 8 stools/day or CRP> 45 mg/L22). All patients (age 18-64) who do not have contraindications to receiving either therapy (as per Canadian product monographs) and have not previously used infliximab or upadacitinib for UC would be potentially eligible for randomization. Patients would be randomized 1:1 to conventional medical rescue therapy with intravenous infliximab as per standard of care (strategy C, as described below) or strategy U, where patients are treated first with upadacitinib 45mg per os (po) daily and only non-responders after 5 days of treatment would stop upadacitinib and be offered infliximab as a sequential second rescue option. All patients will have their steroids standardized at the time of study entry and continue oral prednisone 50mg daily concurrently when initiating medical rescue therapy.
Population: Acute severe ulcerative colitis refractory to intravenous corticosteroids
Intervention: First-line medical rescue therapy with upadacitinib, with option for sequential second-line medical rescue treatment with infliximab in the event of non-response after five days of upadacitinib (strategy U)
Comparison: First-line medical rescue therapy with infliximab (standard of care, strategy C)
Outcome: Treatment success by week 16
Participating Sites
Dr. Singh & Dr. Bernstein, University of Manitoba
Dr. Narula, McMaster University
Dr. Murthy & Dr. McCurdy, Ottawa Hospital Research Institute
Dr. Bessissow & Dr. Afif, McGill University
Dr. Peerani, University of Alberta
Dr. Ma, Dr. Panaccione, and Dr. Lu, University of Calgary
Dr. Jairath and Dr. Khanna, Western University
Dr. Battat, University of Montreal
Dr. Gallinger, Mt. Sinai
Dr. Bressler, University of BC
Targets
Start: May 2025
End: May 2029