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

Post Graduate Institute of Medical Education and Research, Chandigarh

Status: Not yet enrolling

Conditions: Ulcerative Colitis

Treatments: Drug: Cyclosporine; Drug: Tofacitinib

Study type: Interventional

Funder types: Other

Identifiers

NCT05112263

IEC/2021/000641

Details and patient eligibility

About

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

Enrollment: 96 estimated patients

Sex: All

Ages: 18 to 65 years old

Volunteers: No 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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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96 participants in 2 patient groups

Group A

Active Comparator group

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

Treatment:

Drug: Cyclosporine

Group B

Experimental group

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)

Treatment:

Drug: Tofacitinib