Comparison of Medical RESCUE Strategies for Patients With Steroid-refractory Acute Severe Ulcerative Colitis (RESCUE UC)

Comparison of Medical RESCUE Strategies for Patients With Steroid-refractory Acute Severe Ulcerative Colitis: an Open-label Randomized Controlled Trial (RESCUE-UC).

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 Overview

• Status: Recruiting
• Conditions: Colitis, Ulcerative
• Intervention / Treatment: Drug: Upadacitinib Oral Product

Detailed Description

In acute hospitalized severe, steroid refractory UC, only two medical rescue therapies have been found efficacious in controlled trials and recommended in management, infliximab and cyclosporine. Due to toxicity and nuance in using cyclosporine, infliximab is by far the most commonly used medical rescue therapy in this setting. There is emerging retrospective and prospective case series data suggesting JAK inhibitors, such as tofacitinib or upadacitinib, could also be used for this patient population. JAK inhibitors offer potential advantages including convenience of oral therapy, efficacy independent of serum albumin levels, and no concern for immunogenicity as is seen with anti-TNFs. They also offer a short half-life and are eliminated by humans within 48 hours of the last dose administered. This could be beneficial, as it may offer a chance to use a JAK inhibitor first and switch to infliximab in patients who do not respond to a JAK inhibitor, as theoretically cumulative immunosuppression should not be as high transitioning from a JAK inhibitor to infliximab, as compared to using JAK inhibitor after infliximab failure since there will still be lots of infliximab present owing to its long half-life. It is unclear how JAK inhibitors compare to our standard of care and where they should be positioned in acute severe UC. 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 Type: Interventional
• Enrollment (Estimated): 134
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Neeraj Narula; Phone Number: 905-521-2011; Email: neeraj.narula@medportal.ca

Study Locations

• Canada
  • Ontario
    • Hamilton, Ontario, Canada, L8L 2X2
      • Recruiting
      • Hamilton Health Sciences
      • Contact: Neeraj Narula, MD; Phone Number: 905-521-2100; Email: neeraj.narula@medportal.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria: Adult (≥ 18 - 64 years) male or non-pregnant, non-lactating female patients with:

• Confirmed diagnosis of UC, based on conventional clinical, endoscopic, and/or histologic criteria
• Admitted to hospital with acute severe flare and refractory to three days of intravenous steroids (at minimum of 40mg methylprednisolone, or equivalent, daily). Refractory is defined using the Oxford criteria at day 3 of steroid therapy: presence of > 8 stools/day or CRP > 45 mg/L
• Will undergo or has already undergone a baseline colonoscopy or flexible sigmoidoscopy while in hospital or in the 4 weeks preceding trial entry, with a baseline MES ≥2 based on locally evaluated endoscopy
• Provided written informed consent
• Subject is willing and able to adhere to study procedures, and describe in the procedures that screening and safety monitoring procedures will be applied as per upadacitinib and infliximab Canadian product monographs

Exclusion Criteria:

• Contraindications to receiving either infliximab or upadacitinib (as per current Canadian product monograph)
• Previously used infliximab or a JAK inhibitor for UC
• Patients > 65 years of age
• Pregnant or breastfeeding
• Women of reproductive potential who are unwilling to agree to using effective contraception during treatment and 4 weeks following the final dose of upadacitinib
• Concurrent Clostridium difficile, other gastrointestinal infection, or other active systemic or localized infection which would preclude treatment with systemically acting biologic or small molecule therapy
• Patients with symptoms of thrombosis, or confirmed venous or arterial thromboembolism
• Active TB (patients should be tested for TB prior to upadacitinib or infliximab treatment)
• HBV/HCV positive
• Untreated malignancy or ongoing treatment for malignancy
• Concomitant treatment with strong CYP3A4 inhibitors or inducers
• Severe hepatic impairment
• Severe renal impairment (CrCl < 30 ml/min)
• Patients who have received live vaccines in the 28 days prior to study entry.
• Patients with moderate or severe (NYHA Class III/IV) congestive heart failure.
• Patients with a history of hypersensitivity to infliximab, to other murine proteins, or to any of the excipients.
• Patients who are hypersensitive to upadacitinib or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container.

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

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Upadacitinib (treatment arm); Participants will receive Upadacitinib 45mg daily, once a day, for at least five days.	Drug: Upadacitinib Oral Product; Upadacitinib oral 45mg once daily.
No Intervention: Infliximab (standard care); Participants will receive standard care, which is Infliximab.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Measure treatment success of upadacitinib vs standard care.	The primary objective of this study is to evaluate whether treatment success in ASUC patients in patients treated with strategy U is non-inferior to strategy C after 16 weeks of initiating therapeutic management.	16 weeks

Collaborators and Investigators

• Sponsor: McMaster University
• Collaborators: AbbVie

Study record dates

Study Major Dates

• Study Start (Actual): April 16, 2025
• Primary Completion (Estimated): May 1, 2027
• Study Completion (Estimated): September 1, 2027

Study Registration Dates

• First Submitted: October 25, 2024
• First Submitted That Met QC Criteria: October 25, 2024
• First Posted (Actual): October 28, 2024

Study Record Updates

• Last Update Posted (Actual): June 22, 2025
• Last Update Submitted That Met QC Criteria: June 17, 2025
• Last Verified: June 1, 2025

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Intestinal Diseases; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Gastroenteritis; Inflammatory Bowel Diseases; Colitis; Colitis, Ulcerative; Ulcer; Janus Kinase Inhibitors; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antirheumatic Agents; Protein Kinase Inhibitors; Upadacitinib
• Other Study ID Numbers: RESCUE-UC

Drug and device information, study documents

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