A Sequential Multiple Assignment Randomized Trial (SMART) Feasibility Pilot Developing and Optimizing Patient-Tailored Adaptive Treatment Strategies (ATS) for Acute Severe Ulcerative Colitis (ASUC)
Berinstein, Jeffrey
Summary
The goal of this trial is to create personalized treatments for each patient admitted to the hospital with acute severe ulcerative colitis (ASUC). The study will test the feasibility and acceptability of these treatment strategies among patients and physicians so that the study team can later do a larger trial to test whether the medication treatment pathways help patients avoid colectomy while ensuring patient's are safe.
Description
It is anticipated that 62 participants will be enrolled on to the clinical trial and approximately 100 physicians caring for enrolled participants. There is also a third group that are eligible patients not enrolled in the trial (patients will only be interviewed and will not receive any active treatment) and will not be included in the enrollment numbers or outcome measures.
Eligibility
- Age range
- 18–75 years
- Sex
- Female
- Healthy volunteers
- No
Inclusion Criteria for Clinical trial patients: 1. Patient ≥ 18 to 75 years of age at baseline 2. Diagnosis of ulcerative colitis (verified by a typical clinical history as well as characteristic appearance on endoscopy and histology) 3. Current hospital admission for ulcerative colitis treatment (expecting IV corticosteroid initiation) 4. Meeting the following definition of acute severe ulcerative colitis as defined as having ≥ 4 bowel movements per day with visible blood and one of the following: 1. Temperature \> 37.5C 2. Pulse \> 90 BPM 3. Hemoglobin \< 10.5g/dL 4. Erythrocyt…
Interventions
- DrugCyclosporine Injection (IV)
Drug be administered as weight-based continuous infusion (2mg/kg/day) during the second stage of treatment (if applicable). Cyclosporine monitoring will take place approximately 18-24 hours stage of treatment (Day 4 at the earliest). The goal is to achieve whole blood levels of 300 (range 200-400) ng/ml with adjustments according to the table in the protocol. The intravenous cyclosporine dosage is rarely raised above 4 mg/kg/day, in rare patients that are fast metabolizers.
- DrugCyclosporine Oral Product
Once participants meet discharge criteria, participant's that received IV Cyclosporine (stage 2) will be transitioned to oral Cyclosporine. The oral dose is calculated to be approximately twice the daily intravenous dose or approximately 5 mg/kg, rounded to nearest 25 mg, and is administered every 12 hours (h). Oral cyclosporine solution will be administered as Sandimmune capsules available in 25mg 100mg capsules size. After the intervention period (during hospitalization after IV cyclosporine is complete) and during the follow-up period any cyclosporine adjustments are permissible under the current study protocol according to the discretion of the treating physician.
- DrugUpadacitinib Extended Release Oral Tablet
This will be administered orally once daily as 45mg (stage one) or twice daily as a 30mg oral tablet (first stage and second stage) of treatment (if applicable). Upon discharge a patient will be switched from Upadacitinib 30mg twice daily to 45mg daily for 8 weeks followed by 30mg or 15mg subsequently if Upadacitinib is to be continued after discharge. The choice of induction/maintenance agent initiated after discharge will be determined by inpatient treatment team and in consultation with the outpatient gastroenterologist. No patient will continue Upadacitinib 30mg twice daily after discharge from the hospital.
Location
- University of MichiganAnn Arbor, Michigan