TOCASU: Tofacitinib Versus Cyclosporine for Steroid Refractory Acute Severe Ulcerative Colitis

Sponsor
Postgraduate Institute of Medical Education and Research (Other)
Overall Status
Not yet recruiting
CT.gov ID
NCT05112263
Collaborator
All India Institute of Medical Sciences, New Delhi (Other)
96
2
21

Study Details

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

Condition or Disease Intervention/Treatment Phase
N/A

Study Design

Study Type:
Interventional
Anticipated Enrollment :
96 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
Tofacitinib Versus Cyclosporine for Steroid Refractory Acute Severe Ulcerative Colitis: An Open Label Randomized Study
Anticipated Study Start Date :
Jun 1, 2022
Anticipated Primary Completion Date :
May 1, 2023
Anticipated Study Completion Date :
Mar 1, 2024

Arms and Interventions

Arm Intervention/Treatment
Active Comparator: Group A

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

Drug: Cyclosporine
: 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

Experimental: Group B

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)

Drug: Tofacitinib
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

Outcome Measures

Primary Outcome Measures

  1. Treatment failure [14 weeks]

    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

  1. Clinical response [7 days]

    Partial Mayo <4

  2. Absence of steroid free remission [day 98]

    Mayo score of more than 2 with endoscopic sub-score of more than 1

  3. Colectomy free survival [98 days]

    No need for colectomy

  4. Time to clinical response [98 days]

    Partial Mayo of 3 or less

  5. Endoscopic healing [Day 98]

    Mayo endoscopic sub-score of 1 or less

  6. Serious adverse effects [98 days]

    requiring hospitalization, cessation of treatment and events like cardiovascular events, pulmonary embolism, venous thrombosis, any infection, malignancy, gastrointestinal perforation

Eligibility Criteria

Criteria

Ages Eligible for Study:
18 Years to 65 Years
Sexes Eligible for Study:
All
Accepts Healthy Volunteers:
No
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

  • 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

Contacts and Locations

Locations

No locations specified.

Sponsors and Collaborators

  • Postgraduate Institute of Medical Education and Research
  • All India Institute of Medical Sciences, New Delhi

Investigators

  • Principal Investigator: Vishal Sharma, PGIMER Chandigarh
  • Principal Investigator: Vineet Ahuja, AIIMS Delhi

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.
Responsible Party:
Vishal Sharma, Associate Professor, Postgraduate Institute of Medical Education and Research
ClinicalTrials.gov Identifier:
NCT05112263
Other Study ID Numbers:
  • IEC/2021/000641
First Posted:
Nov 8, 2021
Last Update Posted:
Apr 19, 2022
Last Verified:
Apr 1, 2022
Individual Participant Data (IPD) Sharing Statement:
No
Plan to Share IPD:
No
Studies a U.S. FDA-regulated Drug Product:
No
Studies a U.S. FDA-regulated Device Product:
No
Additional relevant MeSH terms:

Study Results

No Results Posted as of Apr 19, 2022