Tofacitinib Versus Cyclosporine for Steroid Refractory Acute Severe Ulcerative Colitis

NCT05112263 | Not Yet Recruiting

• 1 other identifier: IEC/2021/000641
• Study Type: interventional
• Target: 96
• Locations: 0 countries
• Sites: N/A

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

Conditions

Ulcerative Colitis

Outcome Measures

Primary Outcomes (1)

• Treatment failure

  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

  14 weeks

Secondary Outcomes (6)

• Clinical response

  7 days

• Absence of steroid free remission

  day 98

• Colectomy free survival

  98 days

• Time to clinical response

  98 days

• Endoscopic healing

  Day 98

Study Arms (2)

Group A

ACTIVE COMPARATOR

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

Group B

EXPERIMENTAL

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

Interventions

Tofacitinib DRUG

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

Group B

Cyclosporine DRUG

: 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

Group A

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Post Graduate Institute of Medical Education and Research, Chandigarh: lead
• All India Institute of Medical Sciences: collaborator

MeSH Terms

Conditions

Colitis, Ulcerative

Interventions

tofacitinib; Cyclosporine

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Inflammatory Bowel Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Cyclosporins; Peptides, Cyclic; Macrocyclic Compounds; Polycyclic Compounds; Peptides; Amino Acids, Peptides, and Proteins

Study Officials

• Vishal Sharma

  PGIMER Chandigarh

  PRINCIPAL INVESTIGATOR

• Vineet Ahuja

  AIIMS Delhi

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Vishal Sharma

CONTACT

+917087008099; docvishalsharma@gmail.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Study Record Dates

• First Submitted: October 26, 2021
• First Posted: November 8, 2021
• Study Start: July 1, 2023
• Primary Completion: December 1, 2025
• Study Completion: June 1, 2026
• Last Updated: March 29, 2023

Record last verified: 2023-03

Data Sharing

• IPD Sharing: Will not share