Combination Therapy With Infliximab and Tofacitinib for Acute Severe Ulcerative Colitis - CINTO Trial

NCT ID: NCT07297069

Last Updated: 2025-12-24

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

NOT_YET_RECRUITING

Clinical Phase

PHASE2

Total Enrollment

60 participants

Study Classification

INTERVENTIONAL

Study Start Date

2026-01-01

Study Completion Date

2027-12-31

Brief Summary

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In adults hospitalized with acute severe ulcerative colitis who fail to respond to intravenous steroids, does treatment with a combination of infliximab and tofacitinib, compared with infliximab alone or tofacitinib alone, result in higher rates of early clinical remission and mucosal healing, and fewer treatment-related complications over a 10 week period

Detailed Description

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Acute severe ulcerative colitis (ASUC) is a life threatening manifestation of ulcerative colitis that requires urgent medical treatment and hospitalization. Despite the use of rapid induction intravenous corticosteroids, some patients fail to respond and require rescue therapy. Infliximab is commonly used as rescue treatment; however, its effectiveness may be reduced in patients with severe inflammation and hypoalbuminemia. As a result, colectomy rates for ASUC remain significant and improved early rescue strategies are needed.

Tofacitinib is an oral Janus kinase inhibitor that targets multiple cytokine pathways involved in ulcerative colitis. It has a rapid onset of action and has shown benefit in severe and steroid-refractory disease. Because infliximab and tofacitinib act on different immunologic targets, their combined use may provide complementary therapeutic effects. Emerging observational data suggest that combining a biologic agent with a small-molecule therapy may be safe and potentially more effective in patients with severe disease who are at high risk for treatment failure.

This study is designed to explore whether the combination of infliximab and tofacitinib offers greater early clinical benefit compared to infliximab alone, tofacitinib alone for adults hospitalized with ASUC who do not respond to intravenous corticosteroids.The goal is to generate preliminary data that may inform future treatment approaches aimed at improving remission rates, accelerating mucosal healing, and reducing the need for colectomy in this high risk population.

Conditions

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Acute Severe Ulcerative Colitis

Keywords

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Rescue therapy Combination therapy Steroid refractory ulcerative colitis Infliximab Tofacitinib

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Three arm parallel randomized pilot trial comparing infliximab alone, tofacitinib alone, and combination therapy with infliximab plus tofacitinib in adults hospitalized with acute severe ulcerative colitis who do not respond to intravenous corticosteroids.
Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Infliximab Plus Tofacitinib

Participants with acute severe ulcerative colitis who do not respond to intravenous corticosteroids will receive combination therapy with infliximab and tofacitinib. Infliximab 300 mg will be given intravenously, and tofacitinib will be administered orally at 10 mg twice daily. This arm evaluates whether combination therapy produces enhanced early clinical improvement and offers greater effectiveness and safety in inducing early clinical remission and mucosal healing compared with either agent alone.

Group Type EXPERIMENTAL

Infliximab

Intervention Type DRUG

Participants with acute severe ulcerative colitis who do not respond to intravenous corticosteroids will receive infliximab as rescue therapy. Infliximab 300 mg will be administered intravenously. This arm evaluates the effectiveness and safety of infliximab monotherapy in inducing early clinical remission and mucosal healing.

Tofacitinib

Intervention Type DRUG

Participants with acute severe ulcerative colitis who do not respond to intravenous corticosteroids will receive tofacitinib as rescue therapy. Tofacitinib will be administered orally at 10 mg twice daily. This arm assesses the effectiveness and safety of tofacitinib monotherapy in inducing early clinical remission and mucosal healing.

Infliximab Only

Participants with acute severe ulcerative colitis who do not respond to intravenous corticosteroids will receive infliximab alone as rescue therapy. Infliximab will be administered at a dose of 300 mg intravenously according to protocol. This arm evaluates the effectiveness and safety of infliximab monotherapy in inducing early clinical remission and mucosal healing.

Group Type ACTIVE_COMPARATOR

Infliximab

Intervention Type DRUG

Participants with acute severe ulcerative colitis who do not respond to intravenous corticosteroids will receive infliximab as rescue therapy. Infliximab 300 mg will be administered intravenously. This arm evaluates the effectiveness and safety of infliximab monotherapy in inducing early clinical remission and mucosal healing.

Tofacitinib Only

Participants with acute severe ulcerative colitis who do not respond to intravenous corticosteroids will receive tofacitinib alone as rescue therapy. Tofacitinib will be administered orally at 10 mg twice daily. This arm assesses the effectiveness and safety of tofacitinib monotherapy in inducing early clinical remission and mucosal healing.

Group Type ACTIVE_COMPARATOR

Tofacitinib

Intervention Type DRUG

Participants with acute severe ulcerative colitis who do not respond to intravenous corticosteroids will receive tofacitinib as rescue therapy. Tofacitinib will be administered orally at 10 mg twice daily. This arm assesses the effectiveness and safety of tofacitinib monotherapy in inducing early clinical remission and mucosal healing.

Interventions

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Infliximab

Participants with acute severe ulcerative colitis who do not respond to intravenous corticosteroids will receive infliximab as rescue therapy. Infliximab 300 mg will be administered intravenously. This arm evaluates the effectiveness and safety of infliximab monotherapy in inducing early clinical remission and mucosal healing.

Intervention Type DRUG

Tofacitinib

Participants with acute severe ulcerative colitis who do not respond to intravenous corticosteroids will receive tofacitinib as rescue therapy. Tofacitinib will be administered orally at 10 mg twice daily. This arm assesses the effectiveness and safety of tofacitinib monotherapy in inducing early clinical remission and mucosal healing.

Intervention Type DRUG

Eligibility Criteria

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Inclusion Criteria

Adult (aged 18 years to 65 years) patients hospitalised due to ASUC

Exclusion Criteria

1. Patients with UC who did not meet the Truelove Witts criteria for ASUC.
2. Patients who are already on Tofacitinib / Infliximab.
3. Latent or active tuberculosis.
4. Crohn's or Indeterminate colitis.
5. Mega colon (if the diameter of the transverse colon is 5.5 cm or more, with apparent oedema of the bowel wall on plain abdominal radiographs).
6. Pseudomembranous colitis or concomitant CMV colitis.
7. Intestinal perforation.
8. Massive haemorrhage requiring emergency colectomy.
9. Pregnant or lactating female individuals.
10. Current diagnosis or history of thromboembolic disease patients with severe cardiorespiratory, renal or hepatic Co morbidities.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Asian Institute of Gastroenterology, India

OTHER

Sponsor Role lead

Responsible Party

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Mohan Ramchandani

Senior Registrar

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Vamsi Krishna Ankam, DrNB(gastroenterology)

Role: PRINCIPAL_INVESTIGATOR

Asian Institute of Gastroenterology, Hyderabad

Locations

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Asian Institute of Gastroenterology

Hyderabad, Telangana, India

Site Status

Countries

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India

Central Contacts

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Vamsi Krishna Ankam, DrNB(medical gastroenterology)

Role: CONTACT

Phone: +91 9705904243

Email: [email protected]

Pardhu Bharath Neelam, DM (gastroenterology)

Role: CONTACT

Phone: +91 7799456166

Email: [email protected]

Facility Contacts

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Vamsi Krishna Ankam, DrNB(medical gastroenterology)

Role: primary

Pardhu Bharath Neelam, DM(medical gastroenterology)

Role: backup

References

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Hickman K, Jordan R, Sonnier W. Combination biologic and small molecule therapy for refractory ulcerative colitis. Gastroenterology. 2022;162(3 Suppl):S103.

Reference Type BACKGROUND

A genome-scale CRISPR tool for targeting multiple gene family members at once. Nat Plants. 2023 Apr;9(4):511-512. doi: 10.1038/s41477-023-01388-y. No abstract available.

Reference Type BACKGROUND
PMID: 36973416 (View on PubMed)

Other Identifiers

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CINTO 1

Identifier Type: -

Identifier Source: org_study_id