search
Back to results

Tofacitinib Versus Cyclosporine for Steroid Refractory Acute Severe Ulcerative Colitis (TOCASU)

Primary Purpose

Ulcerative Colitis

Status
Not yet recruiting
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Tofacitinib
Cyclosporine
Sponsored by
Postgraduate Institute of Medical Education and Research
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ulcerative Colitis

Eligibility Criteria

18 Years - 65 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Patients admitted with Acute severe ulcerative colitis as defined by Modified Truelove and Witts Criteria WITH Failure to respond to intravenous steroids (Hydrocortisone 100 mg IV QID OR IV Methylprednisolone 60 mg IV OD) as defined by

  • Day 3 non-response as per Oxford criteria (stool frequency of > 8/day, OR stool frequency between 3-8 with CRP > 45 mg/L PLUS
  • Ongoing activity as defined by Partial Mayo Score of > 3 (rectal bleeding sub-score of >1)
  • Decision to start second line therapy (within 5-7 days of starting intravenous steroids)

Exclusion Criteria:

  • Age <18, Age > 65 years

    • E1 disease (involvement distal to rectosigmoid junction only)
    • Crohn's disease

    • Contraindication to intravenous cyclosporine or oral tofacitinib

      • Renal failure, uncontrolled hypertension, seizure disorder,and uncorrected hypomagnesemia (<1.5 mg/L)
      • Previous thrombosis, or prothrombotic state, on oral contraceptive, history of herpes zoster, active TB, active hepatitis, past opportunistic infections, h/o diverticulitis, Age >50 plus at least one cardiac risk factor
    • Patient wants treatment with intravenous infliximab or wants surgery
    • Underlying sepsis or active infection (Enteric infections, Clostridium difficile, active hepatitis B or C, Tuberculosis, zoster, CMV disease)
    • Toxic megacolon, previous dysplasia or any indication of immediate surgery
    • Known malignancy
    • Pregnancy or Lactation
    • Unwilling to provide consent or for follow-up

Sites / Locations

    Arms of the Study

    Arm 1

    Arm 2

    Arm Type

    Active Comparator

    Experimental

    Arm Label

    Group A

    Group B

    Arm Description

    Group A: Intravenous Cyclosporine 2 mg/kg continuous infusion for 5-7 days and then shifted to oral cyclosporine 4 mg/kg/day in two divided doses for 12 weeks

    Oral Tofacitinib 10 mg TDS for 3 days, and then 10 mg BD to complete 8 weeks followed by 5 mg BD till follow-up (14 weeks)

    Outcomes

    Primary Outcome Measures

    Treatment failure
    I) At Day 7 Absence of clinical response at day 7 (as defined by Partial Mayo of > 3) II) By Day 98 Relapse (Partial Mayo Score of 3 or more) between day 7 and day 98 requiring additional therapy Absence of steroid free remission at 14 weeks (Mayo < 2 with MES 1 or less) Need for colectomy, third line medical rescue or biologics or mortality Serious adverse effect needing interruption of treatment

    Secondary Outcome Measures

    Clinical response
    Partial Mayo <4
    Absence of steroid free remission
    Mayo score of more than 2 with endoscopic sub-score of more than 1
    Colectomy free survival
    No need for colectomy
    Time to clinical response
    Partial Mayo of 3 or less
    Endoscopic healing
    Mayo endoscopic sub-score of 1 or less
    Serious adverse effects
    requiring hospitalization, cessation of treatment and events like cardiovascular events, pulmonary embolism, venous thrombosis, any infection, malignancy, gastrointestinal perforation

    Full Information

    First Posted
    October 26, 2021
    Last Updated
    March 27, 2023
    Sponsor
    Postgraduate Institute of Medical Education and Research
    Collaborators
    All India Institute of Medical Sciences, New Delhi
    search

    1. Study Identification

    Unique Protocol Identification Number
    NCT05112263
    Brief Title
    Tofacitinib Versus Cyclosporine for Steroid Refractory Acute Severe Ulcerative Colitis
    Acronym
    TOCASU
    Official Title
    Tofacitinib Versus Cyclosporine for Steroid Refractory Acute Severe Ulcerative Colitis: An Open Label Randomized Study
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    March 2023
    Overall Recruitment Status
    Not yet recruiting
    Study Start Date
    July 1, 2023 (Anticipated)
    Primary Completion Date
    December 1, 2025 (Anticipated)
    Study Completion Date
    June 1, 2026 (Anticipated)

    3. Sponsor/Collaborators

    Responsible Party, by Official Title
    Principal Investigator
    Name of the Sponsor
    Postgraduate Institute of Medical Education and Research
    Collaborators
    All India Institute of Medical Sciences, New Delhi

    4. Oversight

    Studies a U.S. FDA-regulated Drug Product
    No
    Studies a U.S. FDA-regulated Device Product
    No
    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    This randomised trial plans to compare oral tofacitinib with intravenous cyclosporine in patients with acute severe ulcerative colitis who have failed to respond to intravenous steroids

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Ulcerative Colitis

    7. Study Design

    Primary Purpose
    Treatment
    Study Phase
    Not Applicable
    Interventional Study Model
    Parallel Assignment
    Masking
    None (Open Label)
    Allocation
    Randomized
    Enrollment
    96 (Anticipated)

    8. Arms, Groups, and Interventions

    Arm Title
    Group A
    Arm Type
    Active Comparator
    Arm Description
    Group A: Intravenous Cyclosporine 2 mg/kg continuous infusion for 5-7 days and then shifted to oral cyclosporine 4 mg/kg/day in two divided doses for 12 weeks
    Arm Title
    Group B
    Arm Type
    Experimental
    Arm Description
    Oral Tofacitinib 10 mg TDS for 3 days, and then 10 mg BD to complete 8 weeks followed by 5 mg BD till follow-up (14 weeks)
    Intervention Type
    Drug
    Intervention Name(s)
    Tofacitinib
    Intervention Description
    For the tofacitinib the dose of 10 mg BD will be administered for 8 weeks (10 mg TDS for initial three days) and then reduced to 5 mg BD for the period of study
    Intervention Type
    Drug
    Intervention Name(s)
    Cyclosporine
    Intervention Description
    : Intravenous Cyclosporine 2 mg/kg continuous infusion for 5-7 days and then shifted to oral cyclosporine 4 mg/kg/day in two divided doses for 12 weeks.Those who respond with intravenous cyclosporine will be shifted to oral cyclosporine 4 mg/kg for 12 weeks while the thiopurine dose is adjusted to the patient's weight
    Primary Outcome Measure Information:
    Title
    Treatment failure
    Description
    I) At Day 7 Absence of clinical response at day 7 (as defined by Partial Mayo of > 3) II) By Day 98 Relapse (Partial Mayo Score of 3 or more) between day 7 and day 98 requiring additional therapy Absence of steroid free remission at 14 weeks (Mayo < 2 with MES 1 or less) Need for colectomy, third line medical rescue or biologics or mortality Serious adverse effect needing interruption of treatment
    Time Frame
    14 weeks
    Secondary Outcome Measure Information:
    Title
    Clinical response
    Description
    Partial Mayo <4
    Time Frame
    7 days
    Title
    Absence of steroid free remission
    Description
    Mayo score of more than 2 with endoscopic sub-score of more than 1
    Time Frame
    day 98
    Title
    Colectomy free survival
    Description
    No need for colectomy
    Time Frame
    98 days
    Title
    Time to clinical response
    Description
    Partial Mayo of 3 or less
    Time Frame
    98 days
    Title
    Endoscopic healing
    Description
    Mayo endoscopic sub-score of 1 or less
    Time Frame
    Day 98
    Title
    Serious adverse effects
    Description
    requiring hospitalization, cessation of treatment and events like cardiovascular events, pulmonary embolism, venous thrombosis, any infection, malignancy, gastrointestinal perforation
    Time Frame
    98 days

    10. Eligibility

    Sex
    All
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    65 Years
    Accepts Healthy Volunteers
    No
    Eligibility Criteria
    Inclusion Criteria: Patients admitted with Acute severe ulcerative colitis as defined by Modified Truelove and Witts Criteria WITH Failure to respond to intravenous steroids (Hydrocortisone 100 mg IV QID OR IV Methylprednisolone 60 mg IV OD) as defined by Day 3 non-response as per Oxford criteria (stool frequency of > 8/day, OR stool frequency between 3-8 with CRP > 45 mg/L PLUS Ongoing activity as defined by Partial Mayo Score of > 3 (rectal bleeding sub-score of >1) Decision to start second line therapy (within 5-7 days of starting intravenous steroids) Exclusion Criteria: Age <18, Age > 65 years E1 disease (involvement distal to rectosigmoid junction only) Crohn's disease Contraindication to intravenous cyclosporine or oral tofacitinib Renal failure, uncontrolled hypertension, seizure disorder,and uncorrected hypomagnesemia (<1.5 mg/L) Previous thrombosis, or prothrombotic state, on oral contraceptive, history of herpes zoster, active TB, active hepatitis, past opportunistic infections, h/o diverticulitis, Age >50 plus at least one cardiac risk factor Patient wants treatment with intravenous infliximab or wants surgery Underlying sepsis or active infection (Enteric infections, Clostridium difficile, active hepatitis B or C, Tuberculosis, zoster, CMV disease) Toxic megacolon, previous dysplasia or any indication of immediate surgery Known malignancy Pregnancy or Lactation Unwilling to provide consent or for follow-up
    Central Contact Person:
    First Name & Middle Initial & Last Name or Official Title & Degree
    Vishal Sharma
    Phone
    +917087008099
    Email
    docvishalsharma@gmail.com
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Vishal Sharma
    Organizational Affiliation
    PGIMER Chandigarh
    Official's Role
    Principal Investigator
    First Name & Middle Initial & Last Name & Degree
    Vineet Ahuja
    Organizational Affiliation
    AIIMS Delhi
    Official's Role
    Principal Investigator

    12. IPD Sharing Statement

    Plan to Share IPD
    No
    IPD Sharing Plan Description
    The anonymised participant data may be shared on reasonable request

    Learn more about this trial

    Tofacitinib Versus Cyclosporine for Steroid Refractory Acute Severe Ulcerative Colitis

    We'll reach out to this number within 24 hrs