Ulcerative Colitis
Conditions
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
Interventions
DRUGTofacitinib
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
DRUGCyclosporine
: 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
Sponsors
All India Institute of Medical Sciences
Post Graduate Institute of Medical Education and Research, Chandigarh
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
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 \>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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Absence of steroid free remission | day 98 | Mayo score of more than 2 with endoscopic sub-score of more than 1 |
| Colectomy free survival | 98 days | No need for colectomy |
| Clinical response | 7 days | Partial Mayo \<4 |
| Endoscopic healing | Day 98 | Mayo endoscopic sub-score of 1 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 |
| Time to clinical response | 98 days | Partial Mayo of 3 or less |
Contacts
Primary ContactVishal Sharma
Outcome results
None listed