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

Tofacitinib Versus Cyclosporine for Steroid Refractory Acute Severe Ulcerative Colitis: An Open Label Randomized Study

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

Study Overview

• Status: Not yet recruiting
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Cyclosporine; Drug: Tofacitinib

• Study Type: Interventional
• Enrollment (Anticipated): 96
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Vishal Sharma; Phone Number: +917087008099; Email: docvishalsharma@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	14 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Clinical response	Partial Mayo <4	7 days
Absence of steroid free remission	Mayo score of more than 2 with endoscopic sub-score of more than 1	day 98
Colectomy free survival	No need for colectomy	98 days
Time to clinical response	Partial Mayo of 3 or less	98 days
Endoscopic healing	Mayo endoscopic sub-score of 1 or less	Day 98
Serious adverse effects	requiring hospitalization, cessation of treatment and events like cardiovascular events, pulmonary embolism, venous thrombosis, any infection, malignancy, gastrointestinal perforation	98 days

Collaborators and Investigators

• Sponsor: Postgraduate Institute of Medical Education and Research
• Collaborators: All India Institute of Medical Sciences, New Delhi
• Investigators: Principal Investigator: Vishal Sharma, PGIMER Chandigarh; Principal Investigator: Vineet Ahuja, AIIMS Delhi

Study record dates

Study Major Dates

• Study Start (Anticipated): July 1, 2023
• Primary Completion (Anticipated): December 1, 2025
• Study Completion (Anticipated): June 1, 2026

Study Registration Dates

• First Submitted: October 26, 2021
• First Submitted That Met QC Criteria: November 4, 2021
• First Posted (Actual): November 8, 2021

Study Record Updates

• Last Update Posted (Actual): March 29, 2023
• Last Update Submitted That Met QC Criteria: March 27, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Immunosuppressive Agents; Immunologic Factors; Dermatologic Agents; Protein Kinase Inhibitors; Antifungal Agents; Calcineurin Inhibitors; Cyclosporine; Cyclosporins; Tofacitinib
• Other Study ID Numbers: IEC/2021/000641

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: The anonymised participant data may be shared on reasonable request

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No