Upadacitinib-first versus infliximab-only rescue strategy for adults with steroid-refractory acute severe ulcerative colitis.

Is this trial a fit for you?

A plain-English reading of the study's rules. Only the study team can confirm whether you qualify.

What this trial studies

This phase 3 non-inferiority trial compares two medical rescue approaches for adults hospitalized with acute severe ulcerative colitis who have not responded to at least three days of intravenous corticosteroids. One arm gives oral upadacitinib first and uses infliximab for non-responders, while the comparator arm uses infliximab as the initial rescue therapy. Eligible participants must have endoscopic evidence of active disease (MES ≥2) and meet Oxford criteria for steroid refractoriness. The study will follow clinical outcomes and safety to determine whether the upadacitinib-first strategy provides comparable results to infliximab-first care.

Why it matters

Who can join: the full rules

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.

Where it's running

• Hamilton Health Sciences
  Hamilton, Ontario, Canada Recruiting

Study contacts

• Study coordinator: Neeraj Narula
• Email: neeraj.narula@medportal.ca
• Phone: 905-521-2011

Similar studies

Other studies for the same condition or treatment. Recruiting studies are listed first.

• Intestinal ultrasound-guided management for inflammatory bowel disease

  This study tests if adding point-of-care intestinal ultrasound at every visit changes treatment decisions for adults with Crohn’s disease or ulcerative colitis undergoing disease assessment.

  Recruiting Mahidol University · Bangkok · NCT07775352

• Aletekitug safety study in moderate to severe ulcerative colitis

  This sub-study tests whether aletekitug, an anti-IL-18 medication, is safe and tolerable for people with moderately to severely active ulcerative colitis.

  Recruiting Phase 1 GlaxoSmithKline · Oxford · NCT07747480

• Treatment study to test multiple interventions for moderate to severe ulcerative colitis

  This study tests whether a single master protocol can safely test the anti-IL-18 treatment Aletekitug (GSK1070806) in adults with moderate to severe ulcerative colitis to see if it is tolerable and potentially beneficial.

  Recruiting Phase 1 GlaxoSmithKline · Oxford · NCT07747467

• Characterization of Colorectal Dysplastic Lesions and Changes in Risk in IBD Patients

  This study tests how colorectal dysplastic lesions in adults with Crohn disease or ulcerative colitis change over time to help tailor screening and treatment.

  Recruiting at 2 sites Groupe d'Etude Therapeutique des Affections Inflammatoires Digestives · Amiens and 1 other locations · NCT07719426

• Resting energy use in kids with inflammatory bowel disease

  This multicenter study will test the resting energy expenditure of children aged 6–17 with new IBD diagnoses to see how it relates to disease activity and treatment.

  Recruiting Azienda Ospedaliera SS. Antonio e Biagio e Cesare Arrigo di Alessandria · Alessandria, Piedmont · NCT07670975

• Guselkumab in Breast Milk for Lactating Women on Guselkumab

  This study tests how much guselkumab is present in the breast milk of lactating women who are already receiving guselkumab for their approved conditions.

  Recruiting Phase 4 Janssen Research & Development, LLC · Chapel Hill, North Carolina · NCT07654751

How to take part

1. Review the eligibility criteria above with your treating physician.
2. Check the official listing on ClinicalTrials.gov for the latest contact details and recruitment status.
3. Contact the study coordinator or principal investigator to ask for pre-screening. Pre-screening is free and never obligates you to enroll.