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

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.

Conditions

• Ulcerative Colitis Acute

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).

Sponsors & Collaborators

• National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

  collaborator NIH

• Berinstein, Jeffrey

  lead OTHER

Principal Investigators

• Jeffrey Berinstein, MD, MSc · University of Michigan

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Model

SEQUENTIAL

Eligibility

Min Age

18 Years

Max Age

75 Years

Sex

FEMALE

Healthy Volunteers

No

Timeline & Regulatory

Start

2023-09-30

Primary Completion

2026-05-31

Completion

2026-05-31

FDA Drug

Yes

Countries

• United States

Study Locations