Ulcerative Colitis Acute
Adaptive Hospital Drug Strategies for Acute Severe Ulcerative Colitis
This pilot is studying whether sequential, response-guided drug strategies are feasible and acceptable for hospitalized adults with acute severe ulcerative colitis.
Registry title: Feasibility Pilot Sequential Multiple Assignment Randomized Trial (SMART) for Acute Severe Ulcerative Colitis
1 recruiting U.S. site ↓Study at a glance
- Age
- 18 Years–75 Years
- Treatment
- Cyclosporine Injection (IV) or Cyclosporine Oral Product
- Design
- Randomized
- Central study contact
- Queen Saunyama734-647-2564saunayma@umich.edu
- Sponsor
- Berinstein, Jeffrey
Research question
Can response-guided, sequential drug strategies for hospitalized patients with acute severe ulcerative colitis be delivered feasibly and acceptably enough to support a larger trial?
Participant snapshot
Who the study is looking for
- The interventional study is looking for adults ages 18 to 75.
- Participants must have ulcerative colitis confirmed by clinical history, endoscopy, and histology.
- The study is looking for people currently hospitalized, or expected to be admitted, for acute severe ulcerative colitis and expecting intravenous corticosteroids.
- The acute severe episode must include at least four visibly bloody bowel movements per day plus at least one listed systemic, laboratory, weight-loss, or corticosteroid-use feature.
- Participants must have received at least one listed tumor necrosis factor blocker dose, or another approved systemic therapy when those blockers were clinically inadvisable.
Participation overview
What participation may involve
Interventional participants receive a randomized hospital drug strategy, have response assessed on Day 3, and may continue the first therapy or be assigned a second-stage therapy. Follow-up measurements are reported through Day 90, with adverse-event assessment reported for up to 100 days. What participation may involve: - Receive one of the registry-listed methylprednisolone, upadacitinib, or cyclosporine treatment pathways according to random assignment and Day 3 response. - Complete daily bowel-movement symptom surveys and other scheduled study procedures during hospitalization. - Provide reported clinical and research measurements, including blood tests, fecal calprotectin, research stool, and the Ulcerative Colitis Patient-Reported Outcome assessment. - Complete a semi-structured interview about the treatment strategy, study burden, and willingness to join a similar study again. Hospital activities are reported through discharge or colectomy, commonly within an outcome window of approximately 10 days. Follow-up study items are requested on Days 30, 60, and 90, and adverse events are assessed for up to 100 days.
Study interventions
What participants may receive or do
- Cyclosporine Injection (IV): When assigned in the second treatment stage, cyclosporine is given by continuous intravenous infusion at a weight-based dose. Whole-blood levels are monitored and may guide dose adjustments.
- Cyclosporine Oral Product: Participants who receive intravenous cyclosporine and meet discharge criteria transition to oral cyclosporine, generally every 12 hours, with later adjustments left to the treating physician.
- Upadacitinib Extended Release Oral Tablet: Depending on assignment and treatment stage, participants take oral upadacitinib either as 45 milligrams once daily or 30 milligrams twice daily. Any post-discharge regimen is selected by the inpatient team with the outpatient gastroenterologist.
- Intravenous Methylprednisolone: Depending on assignment, methylprednisolone is given intravenously at 30 milligrams twice daily during the first stage and, when applicable, the second stage.
- Prednisone Oral Product: Before discharge, participants who received intravenous methylprednisolone are switched to oral prednisone, with the dose and taper subject to adjustment by the inpatient team in consultation with the outpatient gastroenterologist.
Study design
How the comparison works
This is an open-label, randomized Phase 4 pilot using a Sequential Multiple Assignment Randomized Trial design. Initial response is assessed on Day 3; responders continue their first-stage therapy, while nonresponders undergo a second randomization to a second-stage strategy. Participants in the interventional group are randomized initially. Those classified as nonresponders on Day 3 are randomized again to determine their second-stage therapy. The registry reports no masking, meaning treatment assignments are not blinded. The study also includes a retrospective and prospective observational group of non-enrolled patients hospitalized with acute severe ulcerative colitis during the trial period for comparison with standard-care outcomes.
Reported activities
Procedures and tests
- Clinical response is formally evaluated on Day 3 using predefined protocol criteria.
- Daily bowel-movement symptom surveys and Ulcerative Colitis Patient-Reported Outcome assessments are collected during hospitalization.
- C-reactive protein testing and the Ulcerative Colitis Patient-Reported Outcome assessment are requested before second-stage allocation.
- Day 90 study items include a complete blood count, comprehensive metabolic panel, C-reactive protein, fecal calprotectin, research stool, and a patient-reported outcome assessment.
- The study tracks colectomy status and safety information through 90-day chart review.
- The registry measures completion of an endoscopic evaluation within 72 hours and records whether the endoscopic Mayo score is at least 2.
- Participants complete a semi-structured interview about the acceptability and burden of the trial design before discharge.
- For participants receiving intravenous cyclosporine, whole-blood cyclosporine levels are monitored beginning approximately 18 to 24 hours into that treatment stage.
- The study records adverse events, serious infections, selected events of special interest, and laboratory abnormalities.
Eligibility highlights
Details that may affect whether you contact the study
These are selected highlights, not a complete eligibility check. Exact criteria remain in the full registry record below.
Common requirements
- Participants must be 18 through 75 years old at baseline.
- Ulcerative colitis must be verified through clinical history, endoscopy, and histology.
- The person must currently be hospitalized, or expected to be admitted from the emergency room, for ulcerative colitis treatment with intravenous corticosteroids expected.
- Acute severe ulcerative colitis must involve at least four visibly bloody bowel movements per day plus at least one of the specifically listed clinical, laboratory, weight-loss, or corticosteroid-use features.
- Participants need prior exposure to at least one listed tumor necrosis factor blocker, or at least one approved systemic therapy if those blockers were clinically inadvisable.
- Participants must be willing and able to follow scheduled visits, treatment, laboratory testing, daily symptom surveys, and other study procedures.
- Participants must be able to take oral medication and follow the study drug regimen.
- Females of reproductive potential must have a negative admission pregnancy test and intend to use a listed contraception method throughout the three-month follow-up.
Possible reasons someone may not be able to join
- Other specified forms of colitis or findings suggesting Crohn's disease exclude participation.
- Continuous intravenous corticosteroid treatment for at least 72 hours before enrollment, at any institution, excludes participation.
- People who are currently pregnant or breastfeeding are excluded.
- Meeting the study's diagnostic criteria for toxic megacolon during the current admission excludes participation.
- Prior upadacitinib exposure excludes participation, although prior use of certain other Janus kinase inhibitors is permitted.
- An ongoing severe infection, including untreated or inadequately treated latent or active tuberculosis, may exclude participation as determined by the study team.
- A recent investigational drug or invasive investigational procedure may exclude participation if it could affect ulcerative colitis or interact with study drugs.
- Prior total or subtotal colectomy, an ileoanal or Kock pouch, an ileostomy, or planned bowel surgery excludes participation.
- Specified serious blood-count, kidney, or liver abnormalities exclude participation.
- Certain recent cardiovascular events, coronary stenting, or moderate-to-severe heart failure within the previous six months exclude participation.
Important unknowns
What the record does not make clear
- The record names daily inpatient assessments and study items on Days 30, 60, and 90 but does not give a complete schedule or state which follow-up activities require in-person visits.
- The registry describes assigned study drugs and allows treating-team discretion for some post-discharge choices, but it does not provide a complete list of other ulcerative colitis treatments that may continue, stop, or start.
- The assigned pathways include second-stage rescue therapies, but the record does not fully explain what non-protocol rescue care is available if disease worsens or assigned treatment must stop.
- The registry measures completion of endoscopy within 72 hours and requires prior diagnostic confirmation by endoscopy and histology, but it does not clearly say whether the trial mandates a new endoscopy.
- The record does not state which study drugs, tests, hospital services, or follow-up activities are paid by the study or billed to insurance.
- The record does not report whether participants are paid or reimbursed.
- The record does not describe transportation, lodging, parking, or other travel support.
- Only one recruiting location is listed, and the record does not say whether post-discharge interviews, surveys, laboratory testing, or other follow-up can be completed remotely or locally.
- The record says post-discharge upadacitinib or cyclosporine may be continued under treating-physician discretion, but it does not explain access or payment after study follow-up ends.
- The University of Michigan location is listed as recruiting, but the record includes several interventional, interview, and observational cohorts and does not state separately which cohorts currently have openings.
Before contacting the site
Questions for the study team
- Which initial treatment assignments are currently in use, and what determines the second-stage options available after the Day 3 assessment?
- How do you define a Day 3 responder or nonresponder for the second randomization?
- What is the full inpatient and follow-up schedule, including which Day 30, 60, and 90 activities require travel to Ann Arbor?
- Is a study-specific endoscopy required within 72 hours, or can an endoscopy performed as part of usual care or before enrollment be used?
- What treatment and urgent-care options are available if the assigned drug is not tolerated or the colitis worsens?
- Which study-related drugs, tests, and follow-up services are covered, and could any charges be billed to insurance?
- If upadacitinib or cyclosporine continues after discharge, who prescribes it and how is access arranged after study follow-up?
- Is the randomized interventional cohort currently enrolling, rather than only an interview or observational cohort?
Before changing care
Questions for your gastroenterologist
- How might each listed treatment pathway interact with my current ulcerative colitis medicines and other health conditions?
- How stable or unstable is my current disease, and what usual-care alternatives should be considered alongside this study?
- Would delaying or changing any current treatment for study screening create a clinical concern in my situation?
- What monitoring would you want if I received upadacitinib, cyclosporine, high-dose corticosteroids, or a sequence of these drugs?
- How would you coordinate post-discharge treatment and laboratory follow-up with the inpatient research team?
This plain-language digest is provided by the Aidy clinical trials API. It may omit details and is not medical advice or an eligibility decision. Review the full registry record and confirm details with the study team.
Source record
Full registry record
The sections below preserve the study information supplied through ClinicalTrials.gov, including complete descriptions, criteria, outcomes, and locations.
About this study
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.
Group 1: SMART Intervention (n=62): Adult patients (ages 18+) admitted with Acute Severe Ulcerative Colitis (ASUC) who meet all eligibility criteria and provide informed consent for the interventional component of the trial. Cohort 2: Qualitative Patient Interviews (up to n=38) Eligible patients with ASUC who decline enrollment in the interventional component. These participants will undergo qualitative interviews to identify and characterize barriers to trial participation. Recruitment for this cohort will conclude once thematic saturation is achieved. Cohort 3: Clinician Stakeholder Interviews (up to n=100) Clinicians (including attending physicians and house staff) providing direct care for participants enrolled in the interventional arm. Qualitative interviews will be conducted to assess the feasibility and acceptability of the study protocol within the clinical workflow. Recruitment will conclude once thematic saturation is achieved. Cohort 4: Observational Comparator Group (up to n=500) A retrospective and prospective observational cohort of patients admitted with ASUC during the trial period who were not enrolled in the intervention. This group will serve as a contemporary control to provide comparative data on standard-of-care outcomes and help mitigate selection bias. There was a major amendment (Ame00167573) submitted to the IRBMED and approved. Changes included in the amendment (not all inclusive) were the primary feasibility and acceptability endpoints. New, more granular metrics were added for recruitment, retention, and adherence. These changes were made to provide a more robust and detailed assessment of feasibility, which is the primary goal of this pilot study. Additionally, efficacy outcomes were clarified and expanded as well as some eligibility criteria updated.
Study design and administration
- Organization
- University of Michigan
- Organization class
- Other
- Organization study ID
- HUM00228245
- Lead sponsor
- Berinstein, Jeffrey
- Sponsor class
- Other
- Enrollment type
- Estimated
- Allocation
- Randomized
- Intervention model
- Sequential
- Primary purpose
- Treatment
- Masking
- None
- Who is masked
- Not provided
- Standard age groups
- Adult, Older Adult
Study arms
Experimental
Methylprednisolone
Methylprednisolone Intravenous (IV) 30 milligram (mg) twice a day (BID)
Interventions: Drug: Intravenous Methylprednisolone, Drug: Prednisone Oral Product
Experimental
Methylprednisolone plus Upadacitinib
Methylprednisolone IV 30mg BID plus Upadacitinib 45mg every day.
Interventions: Drug: Upadacitinib Extended Release Oral Tablet, Drug: Intravenous Methylprednisolone
Experimental
Oral Upadacitinib
Upadacitinib 30 mg BID
Interventions: Drug: Upadacitinib Extended Release Oral Tablet
Experimental
Methylprednisolone then Cyclosporine
Methylprednisolone IV 30 mg BID Stage 1 and if determined to be a non-responder to Methylprednisolone, patient will receive rescue Cyclosporine (2milligram/kilogram (mg/kg) per day aiming for levels 200-400 nanograms per milliliter (ng/mL)) in addition to continuing Methylprednisolone for stage 2.
Interventions: Drug: Cyclosporine Injection (IV), Drug: Cyclosporine Oral Product, Drug: Intravenous Methylprednisolone
Experimental
Methylprednisolone then Upadacitinib
Methylprednisolone IV 30mg twice a day Stage 1 and if determined to be a non-responder to Methylprednisolone, patient will receive rescue Upadacitinib 30mg BID in addition to continuing Methylprednisolone for stage 2
Interventions: Drug: Upadacitinib Extended Release Oral Tablet, Drug: Intravenous Methylprednisolone
Experimental
Oral Upadacitinib then Methylprednisolone
Oral Upadacitinib 30mg BID for stage 1 then for patients that are non-responders, add rescue Methylprednisolone IV 30mg twice a day in addition to continuing Upadacitinib for stage 2.
Interventions: Drug: Upadacitinib Extended Release Oral Tablet, Drug: Intravenous Methylprednisolone, Drug: Prednisone Oral Product
Experimental
Oral Upadacitinib then Methylprednisolone plus cyclosporine infusion
Upadacitinib 30 mg BID for stage 1. If a patient is a non-responder to Upadacitinib 30 mg, then the study team will stop Upadacitinib and initiate Methylprednisolone IV 30mg twice a day plus Cyclosporine (2 milligram/kilogram (mg/kg) per day aiming for levels 200-400 nanograms per milliliter (ng/mL)) for stage 2.
Interventions: Drug: Upadacitinib Extended Release Oral Tablet, Drug: Intravenous Methylprednisolone, Drug: Prednisone Oral Product
Experimental
Methylprednisolone plus Upadacitinib then cyclosporine
Methylprednisolone IV 30mg BID and Oral Upadacitinib 45mg everyday stage 1 and then Cyclosporine 2 mg/kg per day aiming for levels 200-400ng/mL for stage 2.
Interventions: Drug: Cyclosporine Injection (IV), Drug: Cyclosporine Oral Product, Drug: Intravenous Methylprednisolone
Experimental
Methylprednisolone plus Upadacitinib then increased Upadacitinib
Methylprednisolone IV 30mg BID and Oral Upadacitinib 45mg everyday stage 1 and if determined to be a non-responder to Methylprednisolone and 45 mg Oral Upadacitinib, patient will receive rescue Upadacitinib 30mg BID in addition to continuing Methylprednisolone for stage 2.
Interventions: Drug: Upadacitinib Extended Release Oral Tablet, Drug: Intravenous Methylprednisolone, Drug: Prednisone Oral Product
Interventions
Drug
Cyclosporine 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.
Drug
Cyclosporine 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.
Drug
Upadacitinib 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.
Drug
Intravenous Methylprednisolone
Drug will be administered as 30mg twice daily during the first stage of treatment (if applicable) and through the second stage of treatment (if applicable). Prior to discharge a patient will be switched from IV Methylprednisolone to prednisone 40-60mg with plans to taper by 5mg/week (dose subject to adjustment by treating inpatient team and in consultation with the outpatient gastroenterologist).
Drug
Prednisone Oral Product
Patients that received IV Methylprednisolone will be switched prior to discharge from IV Methylprednisolone to prednisone 40-60mg with plans to taper by 5mg/week (dose subject to adjustment by treating inpatient team and in consultation with the outpatient gastroenterologist).
Eligibility
18 Years–75 Years
All
Not accepted
Inclusion criteria (19)
- Patient ≥ 18 to 75 years of age at baselineRegistry-derived · unreviewed
- Diagnosis of ulcerative colitis (verified by a typical clinical history as well as characteristic appearance on endoscopy and histology)Registry-derived · unreviewed
- Current hospital admission for ulcerative colitis treatment (expecting IV corticosteroid initiation). Note this includes patients seen in emergency room who are expected to be admitted for UC treatmentRegistry-derived · unreviewed
- 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:Registry-derived · unreviewed
- Temperature \> 37.8 Celsius b. Pulse \> 90 Beats per minute (BPM) c. Hemoglobin \< 10.5g/dL d. Erythrocyte sedimentation rate ≥ 30mm/h e. Weight loss \> 5 lbs over 3 months f. C-reactive protein ≥ 3.0mg/dL g. Fecal calprotectin \>782 mg/kg (within 4 weeks) h. Oral corticosteroid use for ≥ 14 days at a dose equivalent to ≥ 30mg/dayRegistry-derived · unreviewed
- Prior history of receiving at least one dose of adalimumab, certolizumab, infliximab, or golimumab originator or biosimilars or a prior history of receiving at least one approved systemic therapy in the event tumor necrosis factors blockers are clinically inadvisableRegistry-derived · unreviewed
- Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, daily bowel movement symptoms surveys, and other study proceduresRegistry-derived · unreviewed
- Evidence of a personally signed and dated informed consent document indicating that the participant (or a legal representative) has been informed of all pertinent aspects of the studyRegistry-derived · unreviewed
- Ability to take oral medication and be willing to adhere to the study intervention regimenRegistry-derived · unreviewed
- For females of reproductive potential (i.e., females \<55 years of age with intact ovaries and fallopian tubes): A negative pregnancy test on admission and intent to use highly effective contraception during 3-month follow-up period which include the following.Registry-derived · unreviewed
- Combined (estrogen and progestogen containing) hormonal contraception (oral, intravaginal, transdermal, injectable) associated with the inhibition of ovulation, initiated at least 30 days prior to study baselineRegistry-derived · unreviewed
- Progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation, initiated at least 30 days prior to study baselineRegistry-derived · unreviewed
- Bilateral tubal occlusion/ligation (could be via hysteroscopy, provided a hysterosalpingogram confirmed success of the procedure)Registry-derived · unreviewed
- Vasectomized partner(s) provided the vasectomized partner had received medical confirmation of the surgical success and was the sole sexual partner of the trial participantRegistry-derived · unreviewed
- Intrauterine device or intrauterine hormone-releasing systemRegistry-derived · unreviewed
- Lifestyle abstinence (refraining from heterosexual intercourse when this is in line with the preferred and usual lifestyle of the patient)Registry-derived · unreviewed
- Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods)Registry-derived · unreviewed
- Consistent use of barrier contraceptionRegistry-derived · unreviewed
- 1\. Clinicians (Internal medicine residents, gastroenterology fellows, and attending gastroenterologists or colorectal surgeons) caring for the patients enrolled in the clinical trialRegistry-derived · unreviewed
Exclusion criteria (41)
- Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical findings suggestive of Crohn's diseaseRegistry-derived · unreviewed
- On IV corticosteroids for ≥ 72 hours prior to enrollment continuously (at any institution)Registry-derived · unreviewed
- Currently pregnant or breastfeedingRegistry-derived · unreviewed
- Patients who meet diagnostic criteria for toxic megacolon during this current admission. This will be determined by the study team and inpatient treatment team according to the following supportive criteria: Having dilation of the colon \> 6m and three of the following (Temperature\>38 Celsius, Heart Rate \>120 BPM, white blood cells (WBC) \>10500/µL, Hemoglobin \< 10.5mg/dL) and one of the following (dehydration, altered mental status, severe electrolyte disturbances, and hypotension)Registry-derived · unreviewed
- Known hypersensitivity to any of the following drugs or constituents: methylprednisolone, cyclosporine, tofacitinib, or upadacitinibRegistry-derived · unreviewed
- Patients who had previous exposure to upadacitinib. Previous exposure to other Janus kinase (JAK) inhibitors (e.g., tofacitinib, baricitinib, or filgotinib) are permissible.Registry-derived · unreviewed
- Patients with ongoing severe infection (as determined by the study team), including untreated or inadequately treated latent or active tuberculosis (TB)Registry-derived · unreviewed
- Active Cytomegalovirus (CMV) colitis is defined as having \> 5 CMV inclusion bodies per high powered field in any one ulcer at baseline. If CMV colitis is confirmed, the patient can remain in the trial if permissible by the infectious disease and primary treatment team and if concomitant anti-viral therapy is initiated.Registry-derived · unreviewed
- Patients with a positive stool exam for enteric pathogens can remain in the trial. Initiation of treatment at the discretion of the treatment team and infectious disease team if needed.Registry-derived · unreviewed
- Patients who have received any investigational pharmacological agent or invasive investigational procedure within 30 days or five half-lives of study initiation with potential efficacy for UC or that could interact with study medications, as determined by the Principal Investigator. Participation in studies with non-invasive investigational procedures or standard-of-care invasive procedures are permitted.Registry-derived · unreviewed
- Current malignancy with the exception of non-metastatic basal cell or squamous cell carcinoma of the skin.Registry-derived · unreviewed
- Patients who had a history of colectomy (total or subtotal), ileoanal pouch, Kock pouch, or ileostomy or were planning bowel surgeryRegistry-derived · unreviewed
- Moderate or severe renal, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, neurological, or psychiatric condition including the following:Registry-derived · unreviewed
- Neutropenia - Absolute Neutrophil Count (ANC) \<1200 cells/mm3 or Total white blood cell count \<2500/µLRegistry-derived · unreviewed
- Hemoglobin \< 7mg/dL without plans for a transfusionRegistry-derived · unreviewed
- Platelet count \<80,000/µLRegistry-derived · unreviewed
- Moderate/severe renal impairment with estimated glomerular filtration rate (eGFR) \<30milliliter (mL)/min/1.73m2 (by simplified four-variable Modification of Diet in Renal)Registry-derived · unreviewed
- Alanine aminotransferase (ALT) and Aspartate aminotransferase (AST) liver biochemistry levels that are ≥ 2 times the patient's baseline (as determined based on the principal investigator's judgement)Registry-derived · unreviewed
- Cirrhosis with mild to severe hepatic impairment (defined as a Child-Pugh score ≥5)Registry-derived · unreviewed
- History of uncontrolled hypertension (systolic blood pressure \>160 millimeters of mercury (mmHg) or diastolic blood pressure \> 100 millimeters of mercury (mmHg) despite anti-hypertensives)Registry-derived · unreviewed
- Any of the following cardiovascular conditions:Registry-derived · unreviewed
- Recent (within previous 6 months) cerebrovascular accident, myocardial infarction, or coronary stenting b. Recent (within previous 6 months) moderate-to-severe congestive heart failure (New York Heart Association class III or IV)Registry-derived · unreviewed
- History of inherited or acquired conditions that predispose to hypercoagulability including the following. Please note, that patients with a remote history of provoked thrombotic event or recent thrombotic event on systemic anticoagulation are NOT exclusionary.Registry-derived · unreviewed
- Antiphospholipid syndrome b. Factor V Leiden mutation c. Prothrombin G20210A mutations d. Deficiencies of antithrombin f. Deficiency of protein C g. Deficiency of protein S h. Heparin cofactor II deficiency i. Plasminogen and plasminogen activator inhibitor-1 j. Dysfibrinogenemia k. Factor XII deficiencyRegistry-derived · unreviewed
- Patients with total cholesterol \<80 mg/dL at baselineRegistry-derived · unreviewed
- Patients who had a history of an allergic reaction or significant sensitivity to constituents of the treatment (and its excipients) and/or other products in the same class of medication (ex., tofacitinib)Registry-derived · unreviewed
- Patients who had hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection defined as:Registry-derived · unreviewed
- HBV: hepatitis B surface antigen (HBsAg) positive with detectable deoxyribonucleic acid (DNA) not on therapy. Patients with serologic evidence of a resolved prior HBV infection (i.e., HBsAg-negative and anti-HB Core-positive) or patients with HBsAg positive on suppressive HBV therapy with low DNA (\<105 copies/mL or \<104 IU/mL negative) are not exclusionary b. HCV: HCV ribonucleic acid detectable in any patient with anti-HCV antibody c. HIV: Confirmed positive anti-HIV antibody with Cluster of Differentiation 4 (CD4) counts \<350 cells/microliter (uL) or acquired immunodeficiency syndrome (AIDS)- defining opportunist infectionRegistry-derived · unreviewed
- Solid organ or bone marrow transplant within 1 year or expected transplant within 6 monthsRegistry-derived · unreviewed
- History of more than one episode of herpes zoster, a history of disseminated herpes zoster or disseminated herpes simplexRegistry-derived · unreviewed
- Current use of medications which significantly increase the risk of venous thromboembolic event as determined by the investigator including:Registry-derived · unreviewed
- Hormone replacement therapyRegistry-derived · unreviewed
- TestosteroneRegistry-derived · unreviewed
- TamoxifenRegistry-derived · unreviewed
- Vaccination with live or attenuated live vaccines within 6 weeks of baseline or scheduled to receive these vaccines during study period or within 140 days (20 weeks) after last dose of study medication.Registry-derived · unreviewed
- History of any lymphoproliferative disorder (such as Epstein-Barr Virus (EBV)-related lymphoproliferative disorder), history of lymphoma, leukemia, myeloproliferative disorders, multiple myeloma, or signs and symptoms suggestive of current hematologic disease.Registry-derived · unreviewed
- Patients who had a history of spontaneous GI perforation (other than appendicitis or mechanical injury), diverticulitis, or significantly increased risk of GI perforation per investigator's judgementRegistry-derived · unreviewed
- Actively receiving strong CYP3A4 inducers or inhibitors prior to the first dose of study drug or are expected to receive any of these medications during the study period. This includes grapefruit and grapefruit juice.Registry-derived · unreviewed
- The presence of any condition significantly affecting oral drug absorption (e.g., gastrectomy, clinically significant diabetic gastroenteropathy, or certain types of bariatric surgery such as gastric bypass), as determined by the Principal Investigator. Procedures such as gastric banding that simply divide the stomach into separate chambers are NOT exclusionary.Registry-derived · unreviewed
- Patients who had a history of a clinically significant medical condition or any other reason which, in the opinion of the investigator, would have interfered with the patient's participation in this study, would have made the patient an unsuitable candidate to receive treatment, or would have put the patient at risk by participating in the protocolRegistry-derived · unreviewed
- 1\. Non-clinicians not caring for the enrolled patientRegistry-derived · unreviewed
This information can identify a possible match, conflict, or item needing confirmation. Only the study team can determine eligibility.
Study outcomes
Primary outcome
Adherence to intervention based on the proportion of participants who received the assigned Adaptive Treatment Strategy (ATS) (without receiving added/removed therapy outside of assignment) during first stage of therapy
Time frame: Day 3
Target ≥60%
Primary outcome
Adherence to intervention based on the proportion of participants who received the assigned Adaptive Treatment Strategy (ATS) (without receiving added/removed therapy outside of assignment) during second stage of therapy
Time frame: Days 4 through day 10 (maximum 7 days from initiation of second stage of treatment)
Target ≥60%
Primary outcome
Proportion of eligible enrolled patients who were randomized during the first stage of intervention and who received treatment (regardless of ATS assignment)
Time frame: Randomized day 0 - up to day 3
Target ≥ 80%
Primary outcome
Proportion of eligible enrolled patients initiated on first stage therapy who were randomized during second stage of intervention and who received their assigned treatment (regardless of ATS assignment)
Time frame: Days 4 through day 10
Target ≥ 60%
Primary outcome
Proportion of eligible enrolled patients who initiated first stage therapy who successfully transitioned to the second stage of intervention
Time frame: Day 3 - Day 4
Intervention (randomized and received treatment if deemed to be a non-responder or continued treatment/were discharged if deemed to be first stage responder) Target ≥ 50%.
Primary outcome
Proportion of eligible enrolled patients with complete data records for C-Reactive Protein (CRP) and Ulcerative Colitis Patient reported outcomes (UC-PRO) prior to second stage allocation
Time frame: Day 0 to Day 3 of intervention
Target ≥ 60% with CRP and UC-PRO recorded on Day 3 or day of intervention phase completion if occurring before Day 3.
Primary outcome
Proportion of eligible patients who enroll (not including screen failures) in the trial throughout the enrollment period
Time frame: 5 years
Target ≥50%
Primary outcome
Proportion of eligible enrolled participants followed until discharge or colectomy (whichever comes first)
Time frame: up to approximately 10 days
The proportion is regardless of ATS adherence (target ≥ 70%)
Primary outcome
Proportion of eligible enrolled participants without colectomy that were followed for 90 days with completion of one of the required study items
Time frame: 90 days
Participants followed for 90 days with completion of one of the required study items at Day 90 (UC-PRO, Complete Blood Count (CBC), Comprehensive Metabolic Panel (CMP), CRP, fecal calprotectin (FCP), research stool) (target ≥ 70%).
Primary outcome
Proportion of eligible enrolled participants without colectomy that were followed for 90 days with completion of all of the required study items at Day 90
Time frame: 90 days
Proportion of eligible enrolled participants without colectomy that were followed for 90 days with completion of all of the required study items at Day 90 (UC-PRO, CBC, CMP, CRP, FCP, research stool) (target ≥ 50%).
Primary outcome
Percentage of participants with complete colectomy status and safety data via 90-day chart review
Time frame: 90 days
Target ≥ 90%
Primary outcome
Proportion of eligible enrolled participants with complete UC-PROs on each day of hospitalization from enrollment to discharge or colectomy (whichever comes first regardless of intervention phase completion/ATS adherence)
Time frame: up to approximately 10 days
Target ≥ 50% completion across all eligible days
Primary outcome
Proportion of eligible enrolled participants without colectomy that were followed for 90 days with completion of all requested study items
Time frame: Day 30, Day 60, Day 90
Completion of all requested study items at Day 30, Day 60, and Day 90 (target ≥ 50%)
Primary outcome
Proportion of participants who were enrolled prior to receiving their first dose of intravenous (IV) methylprednisolone
Time frame: Baseline
Target ≥ 70%
Primary outcome
Proportion of participants who were enrolled who satisfied Truelove and Witts' disease severity criteria as measured by stool frequency
Time frame: Baseline
This is measured by stool frequency \> 6 Bowel Movements (BMs)/day with blood and 1 feature of systemic disturbance (fever \>37.8 Celsius, pulse \>90 beats/minute, hemoglobin \>10.5 grams per deciliter (g/dL), or erythrocyte sedimentation rate \>30 millimetres per hour (mm/h) or C-reactive protein \>30 mg/L) (target ≥ 50%).
Primary outcome
Proportion of eligible enrolled patients who initiated first stage therapy (regardless of ATS adherence) within 12 hours of randomization
Time frame: up to 12 hours after randomization
Target ≥ 50%
Primary outcome
Proportion of enrolled participants who completed endoscopic evaluation within 72 hours of enrollment and had an endoscopic Mayo score ≥ 2
Time frame: up to 72 hours
This excludes those that did not complete endoscopic evaluation within 1 week of enrollment. Target ≥75%
Primary outcome
Proportion of eligible enrolled participants reporting trial design acceptable as measured by semi-structured interviews
Time frame: up to approximately 10 days (prior to discharge)
Interviews will assess perceptions of the ATS, trial burden, and willingness to participate in a similar study again (target ≥ 60%)
Primary outcome
Proportion of inpatient physicians interviewed reporting trial design acceptable
Time frame: Up to approximately 10 days
Interviews assess the feasibility, practicality, complexity, workload imposed by the SMART design and clarity, and clinical appropriateness of the ATS (target ≥ 60%)
Secondary outcome
Proportion of participants in initial clinical response without rescue therapy or colectomy at 120 hours (5 days) after initiating first stage therapy
Time frame: 5 days
Proportion of enrolled patients meeting the definition of initial clinical response (reduction in bowel movements by ≥60% or \<4 BMs/day AND CRP \< 1 mg/dL).
Secondary outcome
Proportion of participants undergoing same-admission colectomy per first stage treatment and ATS
Time frame: Day 0 to Day 4
Proportion of enrolled patients who undergo colectomy during the index hospitalization.
Secondary outcome
Proportion of participants undergoing 90-day colectomy per first stage treatment and ATS
Time frame: 90 days from enrollment
Proportion of enrolled patients who undergo colectomy during the index hospitalization.
Secondary outcome
Incidence and severity of adverse events
Time frame: Up to 100 days (intervention plus follow-up)
Incidence and severity of adverse events will be reported. Shingles, acne, major cardiovascular events, venous thromboembolic events, cancers and other infections are adverse events of special interest (AESI). The study team will also record the incidence of serious infections and incidence and severity of laboratory abnormalities between first treatment stage and adaptive treatment strategies. Adverse event will be graded as described in the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.
Secondary outcome
Proportion of participants who are in steroid-free remission at 90 days per first stage treatment and ATS.
Time frame: At 90-day follow-up
Proportion of participants without steroid use within 14 days prior to the 90-day follow-up point.
Secondary outcome
Proportion of participants without rescue therapy during intervention period or colectomy within 90 days per first stage treatment and ATS.
Time frame: 90 days
Proportion of enrolled patients who did not receive non-protocol rescue therapy during the intervention period and did not undergo colectomy within 90 days of enrollment.
Secondary outcome
Proportion of participants meeting first stage response criteria per first-stage treatment
Time frame: Day 3
Proportion of participants who met the criteria for being a "responder" at the end of the first stage, out of all participants who received that specific first stage treatment.
Secondary outcome
Proportion of first stage non-responders who are re-randomized who avoid colectomy within 90 days
Time frame: 90 days
Among the subgroup of participants who were non-responders at the end of stage 1 and were re-randomized, the proportion who did not undergo colectomy within 90 days of initial enrollment.
Secondary outcome
Proportion of patients who are steroid-free at 90 days among eligible enrolled patients in SMART compared to non-enrolled patients
Time frame: 90 days
Non-enrolled patients 18-75 years of age, with a verified diagnosis of UC, hospitalized with ASUC (according to the study eligibility criteria) and are expecting IV steroids.
Secondary outcome
Proportion of patients who experience a UC-related readmission within 90 days among eligible enrolled patients in SMART compared to non-enrolled patients
Time frame: 90 days
Non-enrolled patients 18-75 years of age, with a verified diagnosis of UC, hospitalized with ASUC (according to study eligibility criteria) and are expecting IV steroids.
Secondary outcome
Proportion of patients without rescue therapy during hospitalization among eligible enrolled patients in SMART compared to non-enrolled patients
Time frame: Day 0 up to Day 10
Non-enrolled patients 18-75 years of age, with a verified diagnosis of UC, hospitalized with ASUC (according to study eligibility criteria) and are expecting IV steroids.
Secondary outcome
Proportion of patients without rescue therapy during hospitalization or colectomy within 90 days among eligible enrolled patients in SMART compared to non-enrolled patients
Time frame: 90 days
Non-enrolled patients 18-75 years of age, with a verified diagnosis of UC, hospitalized with ASUC (according to our eligibility criteria) and are expecting IV steroids.
Recruiting locations in the United States
University of Michigan
RecruitingAnn Arbor, Michigan, 48109, United States
Queen Saunyama734-647-2564saunayma@umich.edu
Jeffrey Berinstein, MD, MSc
Central study contacts
Registry dates
- First posted
- May 22, 2023
- Primary completion
- Nov 2027
- Overall completion
- Nov 2027
Trial information comes from ClinicalTrials.gov and may change. Confirm current status, eligibility, and site details with the study team. Aidy does not provide medical advice or determine eligibility.