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Ulcerative Colitis AcutePhase 4NCT05867329

Feasibility Pilot Sequential Multiple Assignment Randomized Trial (SMART) for Acute Severe Ulcerative Colitis

A Phase 4 study testing Cyclosporine Injection (IV), Cyclosporine Oral Product and Upadacitinib Extended Release Oral Tablet in people with Ulcerative Colitis Acute, run by Berinstein, Jeffrey at 1 site in United States.

Recruiting

Looking for participants now. Contact the study team or a site below to ask about taking part.

Sites and contacts
Official record
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Trial 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… Read more about this study

Who is it for?
Ages 18 to 75 years
Conditions the study is for
Ulcerative Colitis Acute
What is being tested?
Cyclosporine Injection (IV), Cyclosporine Oral Product and Upadacitinib Extended Release Oral Tablet
Could I receive a placebo?
No, everyone receives an active treatment
How many people
700 participants
Where
1 siteUnited States
Study dates
30 Sep 2023to Nov 2027
Phase
Phase 4
Are there results?
Not yet: the study is under way

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 75 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Patient ≥ 18 to 75 years of age at baseline
  • Diagnosis of ulcerative colitis (verified by a typical clinical history as well as characteristic appearance on endoscopy and histology)
  • 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 treatment
  • 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:
  • 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/day
  • 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 inadvisable
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  • Participants who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, daily bowel movement symptoms surveys, and other study procedures
  • 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 study
  • Ability to take oral medication and be willing to adhere to the study intervention regimen
  • 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.
  • 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 baseline
  • Progestogen-only hormonal contraception (oral, injectable, implantable) associated with inhibition of ovulation, initiated at least 30 days prior to study baseline
  • Bilateral tubal occlusion/ligation (could be via hysteroscopy, provided a hysterosalpingogram confirmed success of the procedure)
  • Vasectomized partner(s) provided the vasectomized partner had received medical confirmation of the surgical success and was the sole sexual partner of the trial participant
  • Intrauterine device or intrauterine hormone-releasing system
  • Lifestyle abstinence (refraining from heterosexual intercourse when this is in line with the preferred and usual lifestyle of the patient)
  • Periodic abstinence (e.g., calendar, ovulation, symptothermal, postovulation methods)
  • Consistent use of barrier contraception
  • 1. Clinicians (Internal medicine residents, gastroenterology fellows, and attending gastroenterologists or colorectal surgeons) caring for the patients enrolled in the clinical trial

Who cannot join

  • Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical findings suggestive of Crohn's disease
  • On IV corticosteroids for ≥ 72 hours prior to enrollment continuously (at any institution)
  • Currently pregnant or breastfeeding
  • 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)
  • Known hypersensitivity to any of the following drugs or constituents: methylprednisolone, cyclosporine, tofacitinib, or upadacitinib
  • Patients who had previous exposure to upadacitinib. Previous exposure to other Janus kinase (JAK) inhibitors (e.g., tofacitinib, baricitinib, or filgotinib) are permissible.
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  • Patients with ongoing severe infection (as determined by the study team), including untreated or inadequately treated latent or active tuberculosis (TB)
  • 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.
  • 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.
  • 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.
  • Current malignancy with the exception of non-metastatic basal cell or squamous cell carcinoma of the skin.
  • Patients who had a history of colectomy (total or subtotal), ileoanal pouch, Kock pouch, or ileostomy or were planning bowel surgery
  • Moderate or severe renal, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, neurological, or psychiatric condition including the following:
  • Neutropenia - Absolute Neutrophil Count (ANC) <1200 cells/mm3 or Total white blood cell count <2500/µL
  • Hemoglobin < 7mg/dL without plans for a transfusion
  • Platelet count <80,000/µL
  • Moderate/severe renal impairment with estimated glomerular filtration rate (eGFR) <30milliliter (mL)/min/1.73m2 (by simplified four-variable Modification of Diet in Renal)
  • 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)
  • Cirrhosis with mild to severe hepatic impairment (defined as a Child-Pugh score ≥5)
  • History of uncontrolled hypertension (systolic blood pressure >160 millimeters of mercury (mmHg) or diastolic blood pressure > 100 millimeters of mercury (mmHg) despite anti-hypertensives)
  • Any of the following cardiovascular conditions:
  • 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)
  • 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.
  • 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 deficiency
  • Patients with total cholesterol <80 mg/dL at baseline
  • 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)
  • Patients who had hepatitis B virus (HBV), hepatitis C virus (HCV), or human immunodeficiency virus (HIV) infection defined as:
  • 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 infection
  • Solid organ or bone marrow transplant within 1 year or expected transplant within 6 months
  • History of more than one episode of herpes zoster, a history of disseminated herpes zoster or disseminated herpes simplex
  • Current use of medications which significantly increase the risk of venous thromboembolic event as determined by the investigator including:
  • Hormone replacement therapy
  • Testosterone
  • Tamoxifen
  • 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.
  • 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.
  • 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 judgement
  • 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.
  • 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.
  • 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 protocol
  • 1. Non-clinicians not caring for the enrolled patient

Trial locations and contacts

1 site in 1 country. Contact the study team or a site near you to ask about taking part.

Queen Saunyama contact

734-647-2564

saunayma@umich.edu

United States1 site, 1 recruiting

  • University of Michigan

    Ann Arbor, Michigan, 48109

    Queen Saunyama, 734-647-2564, saunayma@umich.edu

    Jeffrey Berinstein, MD, MSc

    Recruiting

Other trials in United States

About this study

Official title: A Sequential Multiple Assignment Randomized Trial (SMART) Feasibility Pilot Developing and Optimizing Patient-Tailored Adaptive Treatment Strategies (ATS) for Acute Severe Ulcerative Colitis (ASUC)

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.

Read the detailed description

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.

Being tested
Cyclosporine Injection (IV), Cyclosporine Oral Product, Upadacitinib Extended Release Oral Tablet, Intravenous Methylprednisolone, Prednisone Oral Product
Keywords
Acute Severe Ulcerative Colitis, Ulcerative colitis flare

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Cyclosporine Injection (IV)Drug

    Also called Sandimmune

    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.

  • Cyclosporine Oral ProductDrug

    Also called Sandimmune

    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.

  • Upadacitinib Extended Release Oral TabletDrug

    Also called Rinvoq

    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.

  • Intravenous MethylprednisoloneDrug

    Also called Solu-Medrol

    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).

  • Prednisone Oral ProductDrug

    Also called Rayos

    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).

Study groups in NCT05867329
Study groupRoleWhat they receive
MethylprednisoloneExperimentalMethylprednisolone Intravenous (IV) 30 milligram (mg) twice a day (BID)
Receives: Drug: Intravenous Methylprednisolone; Drug: Prednisone Oral Product
Methylprednisolone plus UpadacitinibExperimentalMethylprednisolone IV 30mg BID plus Upadacitinib 45mg every day.
Receives: Drug: Upadacitinib Extended Release Oral Tablet; Drug: Intravenous Methylprednisolone
Oral UpadacitinibExperimentalUpadacitinib 30 mg BID
Receives: Drug: Upadacitinib Extended Release Oral Tablet
Methylprednisolone then CyclosporineExperimentalMethylprednisolone 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.
Receives: Drug: Cyclosporine Injection (IV); Drug: Cyclosporine Oral Product; Drug: Intravenous Methylprednisolone
Methylprednisolone then UpadacitinibExperimentalMethylprednisolone 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
Receives: Drug: Upadacitinib Extended Release Oral Tablet; Drug: Intravenous Methylprednisolone
Oral Upadacitinib then MethylprednisoloneExperimentalOral 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.
Receives: Drug: Upadacitinib Extended Release Oral Tablet; Drug: Intravenous Methylprednisolone; Drug: Prednisone Oral Product
Oral Upadacitinib then Methylprednisolone plus cyclosporine infusionExperimentalUpadacitinib 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.
Receives: Drug: Upadacitinib Extended Release Oral Tablet; Drug: Intravenous Methylprednisolone; Drug: Prednisone Oral Product
Methylprednisolone plus Upadacitinib then cyclosporineExperimentalMethylprednisolone 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.
Receives: Drug: Cyclosporine Injection (IV); Drug: Cyclosporine Oral Product; Drug: Intravenous Methylprednisolone
Methylprednisolone plus Upadacitinib then increased UpadacitinibExperimentalMethylprednisolone 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.
Receives: Drug: Upadacitinib Extended Release Oral Tablet; Drug: Intravenous Methylprednisolone; Drug: Prednisone Oral Product

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Target ≥60%

    Measured: Day 3

  2. 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

    Target ≥60%

    Measured: Days 4 through day 10 (maximum 7 days from initiation of second stage of treatment)

  3. Proportion of eligible enrolled patients who were randomized during the first stage of intervention and who received treatment (regardless of ATS assignment)

    Target ≥ 80%

    Measured: Randomized day 0 - up to day 3

  4. 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)

    Target ≥ 60%

    Measured: Days 4 through day 10

  5. Proportion of eligible enrolled patients who initiated first stage therapy who successfully transitioned to the second stage of intervention

    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%.

    Measured: Day 3 - Day 4

  6. 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

    Target ≥ 60% with CRP and UC-PRO recorded on Day 3 or day of intervention phase completion if occurring before Day 3.

    Measured: Day 0 to Day 3 of intervention

  7. Proportion of eligible patients who enroll (not including screen failures) in the trial throughout the enrollment period

    Target ≥50%

    Measured: 5 years

  8. Proportion of eligible enrolled participants followed until discharge or colectomy (whichever comes first)

    The proportion is regardless of ATS adherence (target ≥ 70%)

    Measured: up to approximately 10 days

  9. Proportion of eligible enrolled participants without colectomy that were followed for 90 days with completion of one of the required study items

    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%).

    Measured: 90 days

  10. 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

    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%).

    Measured: 90 days

  11. Percentage of participants with complete colectomy status and safety data via 90-day chart review

    Target ≥ 90%

    Measured: 90 days

  12. 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)

    Target ≥ 50% completion across all eligible days

    Measured: up to approximately 10 days

  13. Proportion of eligible enrolled participants without colectomy that were followed for 90 days with completion of all requested study items

    Completion of all requested study items at Day 30, Day 60, and Day 90 (target ≥ 50%)

    Measured: Day 30, Day 60, Day 90

  14. Proportion of participants who were enrolled prior to receiving their first dose of intravenous (IV) methylprednisolone

    Target ≥ 70%

    Measured: Baseline

  15. Proportion of participants who were enrolled who satisfied Truelove and Witts' disease severity criteria as measured by stool frequency

    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%).

    Measured: Baseline

  16. Proportion of eligible enrolled patients who initiated first stage therapy (regardless of ATS adherence) within 12 hours of randomization

    Target ≥ 50%

    Measured: up to 12 hours after randomization

  17. Proportion of enrolled participants who completed endoscopic evaluation within 72 hours of enrollment and had an endoscopic Mayo score ≥ 2

    This excludes those that did not complete endoscopic evaluation within 1 week of enrollment.

    Target ≥75%

    Measured: up to 72 hours

  18. Proportion of eligible enrolled participants reporting trial design acceptable as measured by semi-structured interviews

    Interviews will assess perceptions of the ATS, trial burden, and willingness to participate in a similar study again (target ≥ 60%)

    Measured: up to approximately 10 days (prior to discharge)

  19. Proportion of inpatient physicians interviewed reporting trial design acceptable

    Interviews assess the feasibility, practicality, complexity, workload imposed by the SMART design and clarity, and clinical appropriateness of the ATS (target ≥ 60%)

    Measured: Up to approximately 10 days

Secondary outcomes (12)

  1. Proportion of participants in initial clinical response without rescue therapy or colectomy at 120 hours (5 days) after initiating first stage therapy

    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).

    Measured: 5 days

  2. Proportion of participants undergoing same-admission colectomy per first stage treatment and ATS

    Proportion of enrolled patients who undergo colectomy during the index hospitalization.

    Measured: Day 0 to Day 4

  3. Proportion of participants undergoing 90-day colectomy per first stage treatment and ATS

    Proportion of enrolled patients who undergo colectomy during the index hospitalization.

    Measured: 90 days from enrollment

  4. Incidence and severity of adverse events

    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.

    Measured: Up to 100 days (intervention plus follow-up)

  5. Proportion of participants who are in steroid-free remission at 90 days per first stage treatment and ATS.

    Proportion of participants without steroid use within 14 days prior to the 90-day follow-up point.

    Measured: At 90-day follow-up

  6. Proportion of participants without rescue therapy during intervention period or colectomy within 90 days per first stage treatment and ATS.

    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.

    Measured: 90 days

  7. Proportion of participants meeting first stage response criteria per first-stage treatment

    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.

    Measured: Day 3

  8. Proportion of first stage non-responders who are re-randomized who avoid colectomy within 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.

    Measured: 90 days

  9. Proportion of patients who are steroid-free at 90 days among eligible enrolled patients in SMART compared to non-enrolled patients

    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.

    Measured: 90 days

  10. Proportion of patients who experience a UC-related readmission within 90 days among eligible enrolled patients in SMART compared to non-enrolled patients

    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.

    Measured: 90 days

  11. Proportion of patients without rescue therapy during hospitalization among eligible enrolled patients in SMART compared to non-enrolled patients

    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.

    Measured: Day 0 up to Day 10

  12. Proportion of patients without rescue therapy during hospitalization or colectomy within 90 days among eligible enrolled patients in SMART compared to non-enrolled patients

    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.

    Measured: 90 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 May 2023
  2. Study start30 Sep 2023
  3. Primary completionNov 2027 (estimated)
  4. Study completionNov 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 4
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Sequential
Model description
This study utilizes a Sequential Multiple Assignment Randomized Trial (SMART) design to evaluate adaptive treatment strategies for patients with Acute Severe Ulcerative Colitis (ASUC). Stage 1 Intervention: Upon enrollment, patients are randomized to an initial treatment arm. Clinical response is formally evaluated on Day 3 using pre-defined protocol criteria. Participants meeting response criteria at Day 3 will remain on their initially assigned Stage 1 therapy through the remainder of the induction period while participants identified as non-responders at Day 3 will undergo a second randomization to determine their Stage 2 therapy. The study will include semi-structured interviews with the inpatient clinical teams to evaluate the feasibility of the sequential randomization and the acceptability. The study will also include a Matched Temporal Control Group consisting of non-enrolled patients admitted with ASUC during the concurrent study period for a comparative analysis.
Masking
None (open label)
Enrolment
700 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT05867329
Sponsor's protocol ID
HUM00228245
Other IDs
K23DK134764
Status last verified
Aug 2026
First submitted
18 Apr 2023
Last updated
11 Aug 2026
Results posted
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
Yes: Data sharing plan includes: \* de-identified dataset will be placed in a public repository after publication.

Publications

  • Honap S, Jairath V, Sands BE, Dulai PS, Danese S, Peyrin-Biroulet L. Acute severe ulcerative colitis trials: the past, the present and the future. Gut. 2024 Sep 9;73(10):1763-1773. doi: 10.1136/gutjnl-2024-332489.

    PubMed 38834296

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Cyclosporine Injection (IV), Cyclosporine Oral Product and Upadacitinib Extended Release Oral Tablet in people with Ulcerative Colitis Acute, run by Berinstein, Jeffrey at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 19 inclusion and 41 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: looking for participants now, as of the sponsor's last update on 11 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Queen Saunyama (734-647-2564, saunayma@umich.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 19 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05867329, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 11 Aug 2026.

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