To study the effect of Tofacitinib along with corticosteroids in patients with acute severe ulcerative colitis.
- Conditions
- Ulcerative colitis, unspecified,
- Registration Number
- CTRI/2022/08/044613
- Lead Sponsor
- Dr Ajit Sood
- Brief Summary
Ulcerative Collitis (UC) is a chronic immune-mediated inflammatory
condition of the large intestine that is frequently associated with
inflammation of the rectum but often extends proximally to involve
additional areas of the colon. The absence of rectal involvement has
been noted in fewer than 5% of adult patients with UC at diagnosis but
may be seen in up to one-third of pediatric-onset colitis. Determination of the extent and severity of disease is important to
select the appropriate treatment algorithm. Extent of the disease
should be characterized according to the Montreal classification as
proctitis (E1), left-sided colitis (E2), or extensive colitis (E3) (extension
proximal to the splenic flexure). [4,5] Commonly, severity of UC has been
classified according to the Truelove and Witts’ [6] criteria published in
1955. Mild colitis is defined as fewer than 4 bowel movements daily,
normal temperature, heart rate, hemoglobin (>11 g/dL), and ESR (<20
mm/hr). Severe disease is defined by bowel frequency greater than 6
times a day in conjunction with fever, tachycardia, anemia, or an
elevation in ESR. Tofacitinib, a JAK-STAT (Janus kinase-signal transducers and
activators of transcription) inhibitor and an anti-inflammatory drug, is a
new addition to the treatment modalities for UC. Janus kinases are
intracellular tyrosine kinases which mediate the signal transduction of
various cytokines involved in the inflammatory reactions in IBD, like IL-
6, IL-7, Il-10, IL-12, IFNα, IFNβ 2, 4, 7, 9 etc. The advantages of JAK-
STAT inhibitors over monoclonal antibodies include, the oral
administration, predictable pharmacokinetics with reduced plasma half-
life, rapid onset of action, quick clearance, lack of immunogenicity and
an intracellular target.
This is a placebo controlled randomized clinical study in subjects with
ASUC.
Patients with acute severe UC (defined as 6 or more stools with blood
and 1 or more of the following hemoglobin <10.5 g/dL, erythrocyte
sedimentation rate [ESR] >30 mm/hr or CRP > 30 mg/L, fever >37.8°C,
or tachycardia >90/min; the modified Truelove Witts criteria) and
fulfilling all other inclusion/exclusion criteria will be randomized. A
computer-generated randomization schedule will be used to assign
subjects to either of the two groups at a 1:1 allocation ratio.
Group 1 : Intravenous hydrocortisone (300 mg per day in three divided
doses) plus Tofacitinib (10 mg thrice daily) for 7 days
Group 2 : Intravenous hydrocortisone (300 mg per day in three divided
doses) plus Placebo (thrice daily) for 7 days.
Patients who fail to respond to treatment (defined as patients with >8
stools/day, or 3–8 stools/day with CRP >45 mg/L between days 3 and
5), necessitating initiation of salvage medical therapy
(biologics/cyclosporine) or colectomy would be started on appropriate
treatment at the discretion of the investigator.
Confirmed cases of IBD will be enrolled and the appropriate
investigations will be done. Daily stool frequency and questionnaire will
be filled. Patients will be followed-up every day for first 7 days followed
by on day 14 and after 8 weeks from the day of enrollment.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Suspended
- Sex
- All
- Target Recruitment
- 100
- Patients with acute severe ulcerative colitis (defined by Truelove Witts Criteria) 2.
- Subject must be at least 18 years of age.
- Subjects who are willing and able to comply with treatment plan, laboratory tests, daily bowel movement diary call, and other study procedures.
- Subjects who are willing to provide a written informed consent.
- Presence of indeterminate colitis, microscopic colitis, ischemic colitis, infectious colitis, or clinical findings suggestive of Crohn’s Disease.
- Subjects displaying clinical signs of fulminant colitis or toxic megacolon 3.
- Subjects infected with human immunodeficiency virus (HIV) or hepatitis B or C viruses 4.
- Subjects who have been vaccinated with live or attenuated vaccine within 6 weeks of baseline or scheduled to receive these vaccines during study period or within 6 weeks after last dose of study medication 12 5.
- Subjects with malignancies or a history of malignancies, with the exception of adequately treated or excised non-metastatic basal cell or squamous cell cancer of the skin.
- Subjects with current or recent history of severe, progressive, or uncontrolled renal, hepatic, hematological, gastrointestinal, metabolic, endocrine, pulmonary, cardiac, neurological disease.
- Pregnant females.
Study & Design
- Study Type
- Interventional
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method The effectiveness of tofacitinib as adjunctive 7 days Drug or placebo therapy | 14th day Follow up | 8 weeks Follow up therapy to intravenous hydrocortisone in patients with ASUC will be evaluated. 7 days Drug or placebo therapy | 14th day Follow up | 8 weeks Follow up This will see the response of tofacitinib in achieving remission in patients with ASUC 7 days Drug or placebo therapy | 14th day Follow up | 8 weeks Follow up
- Secondary Outcome Measures
Name Time Method The effectiveness of Tofacitinib in patients with ASUC. After 8 weeks Follow up
Trial Locations
- Locations (1)
Dayanand Medical College and Hospital
🇮🇳Ludhiana, PUNJAB, India
Dayanand Medical College and Hospital🇮🇳Ludhiana, PUNJAB, IndiaDr Ajit SoodPrincipal investigator9815400718ajitsood10@gmail.com