Tofacitinib Versus Cyclosporine for Steroid Refractory Acute Severe Ulcerative Colitis
- Conditions
- Ulcerative Colitis
- Interventions
- Registration Number
- NCT05112263
- Lead Sponsor
- Post Graduate Institute of Medical Education and Research, Chandigarh
- 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
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- NOT_YET_RECRUITING
- Sex
- All
- Target Recruitment
- 96
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)
-
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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Group A Cyclosporine 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 Group B Tofacitinib 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)
- Primary Outcome Measures
Name Time Method 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
1. Relapse (Partial Mayo Score of 3 or more) between day 7 and day 98 requiring additional therapy
2. Absence of steroid free remission at 14 weeks (Mayo \< 2 with MES 1 or less)
3. Need for colectomy, third line medical rescue or biologics or mortality
4. Serious adverse effect needing interruption of treatment
- Secondary Outcome Measures
Name Time Method Endoscopic healing Day 98 Mayo endoscopic sub-score of 1 or less
Clinical response 7 days Partial Mayo \<4
Colectomy free survival 98 days No need for colectomy
Time to clinical response 98 days Partial Mayo of 3 or less
Serious adverse effects 98 days requiring hospitalization, cessation of treatment and events like cardiovascular events, pulmonary embolism, venous thrombosis, any infection, malignancy, gastrointestinal perforation
Absence of steroid free remission day 98 Mayo score of more than 2 with endoscopic sub-score of more than 1