Upadacitinib-first versus infliximab-only rescue strategy for adults with steroid-refractory acute severe ulcerative colitis.
Comparison of Medical RESCUE Strategies for Patients With Steroid-refractory Acute Severe Ulcerative Colitis: an Open-label Randomized Controlled Trial (RESCUE-UC).
This trial tests whether giving upadacitinib first and switching to infliximab only if needed works as well as starting with infliximab alone for adults hospitalized with steroid-refractory acute severe ulcerative colitis.
Quick facts
| Phase | Phase 3 |
|---|---|
| Study type | Interventional |
| Enrollment | 134 (estimated) |
| Ages | 18 Years to 64 Years |
| Sex | All |
| Sponsor | McMaster University Academic / other |
| Drugs / interventions | infliximab, upadacitinib, tofacitinib |
| Locations | 1 site (Hamilton, Ontario) |
| Trial ID | NCT06660693 on ClinicalTrials.gov |
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.
Who should consider this trial
Good fit: Adults aged 18–64 who are hospitalized with acute severe UC, remain steroid-refractory after at least three days of IV steroids, have a baseline endoscopy with MES ≥2, and can provide informed consent are the intended participants.
Not a fit: Patients who are pregnant or breastfeeding, have contraindications to JAK inhibitors or infliximab, are outside the specified age range, or do not have steroid-refractory hospitalized disease are unlikely to benefit from this protocol.
Why it matters
Potential benefit: If successful, this approach could provide a convenient oral rescue option that shortens exposure to prolonged biologic immunosuppression and may reduce the need for surgery.
How similar studies have performed: Retrospective and prospective case series have suggested JAK inhibitors such as tofacitinib or upadacitinib may help in this setting, but randomized controlled evidence comparing a JAK-first versus infliximab-first strategy is limited.
Eligibility criteria
Show full inclusion / exclusion criteria
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 this trial is running
Hamilton, Ontario
- Hamilton Health Sciences — Hamilton, Ontario, Canada (Recruiting)
Study contacts
- Study coordinator: Neeraj Narula
- Email: neeraj.narula@medportal.ca
- Phone: 905-521-2011
How to participate
- Review the eligibility criteria above with your treating physician.
- Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
- Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.