Multi-center Acute Severe Ulcerative Colitis Cohort Study (MASCC)

Completed

• Conditions: Ulcerative Colitis
• Interventions: Other: Standard of care

• Registration Number: NCT03669822
• Lead Sponsor: Johns Hopkins University

Brief Summary

Ulcerative colitis (UC) is a chronic, progressive immunologically mediated disease affecting nearly 1 million Americans. Up to one third of patients with UC will require hospitalization for severe disease (termed 'acute severe colitis (ASUC)'), often within the first year after diagnosis. Investigators will develop a large multi-center cohort of patients with ASUC with homogeneously collected detailed longitudinal clinical and laboratory data.

Detailed Description

Ulcerative colitis (UC) is a chronic, progressive immunologically mediated disease affecting nearly 1 million Americans. Up to one third of patients with UC will require hospitalization for severe disease (termed 'acute severe colitis (ASUC)'), often within the first year after diagnosis. Advances in therapy for UC with the availability of effective biologics have revolutionized the medical care of UC, improving ability to achieve remission and reducing the need for colectomy for refractory disease. However, despite this general progress, investigators have not witnessed a corresponding temporal improvement in disease outcomes among those with the most severe disease. As well, providers lack the ability to 'personalize' care for UC by predicting up front which patients may develop ASUC or fail medical therapy and may benefit from early surgery, preventing protracted morbidity.

Over one-third of patients with ASUC will be refractory to intravenous steroids, the cornerstone for initial management of this condition. Infliximab and cyclosporine, the two most commonly used medical rescue therapies for this cohort, have comparable short- and long-term efficacy in two randomized controlled trials. However, up to a third of patients will not respond to such medical rescue. Lack of response is poorly understood and may be multifactorial with both patient- and drug-related factors. Among the latter, those with severe disease may have greater fecal loss of infliximab resulting in lack of efficacy. Attempts to overcome this have included accelerated induction with infliximab administered up front at a higher dose (10mg/kg) or more frequent intervals. A small single center retrospective study of only 50 patients among whom 15 received accelerated induction showed reduced short-term but not long-term rates of colectomy with this approach. However, a robust and generalizable comparison of the two infliximab induction treatment strategies are lacking. A key factor limiting study of ASUC is the lack of availability of large cohorts with detailed clinical information and linked specimens.

Here, investigators will develop a large multi-center cohort of patients with ASUC with homogeneously collected detailed longitudinal clinical and laboratory data. To the investigators' knowledge, this will be the first of its kind in the United States, and will be a key resource to understand the natural history, risk stratify and optimize therapeutic algorithms for care of patients with ASUC. A sub-study with blood, stool and biopsy specimens can be utilized for translational research into mechanisms of lack of response and development of biomarkers. The infrastructure of this network will also serve as a valuable resource for clinical trials of new therapies and novel strategies, a significant unmet need.

Study Timeline

• Study First Submitted: 2018-05-29
• Study First Submitted QC: 2018-09-11
• Study First Posted: 2018-09-13
• Study Start: 2018-11-10
• Primary Completion: 2024-12-31
• Study Completion: 2024-12-31
• Status Verified: 2025-01
• Last Update Submitted: 2025-01-22
• Last Update Posted: 2025-01-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 97

Inclusion Criteria

• Patients 18-80 years
• UC or IBD-unspecified (IBDU) diagnosed according to standard criteria
• Active disease defined as Simple Clinical Colitis Activity Index > 2 (day/night bowel frequency, urgency with defecation, blood in stool, general well-being, and extracolonic features)
• Admitted to the hospital
• Initiating intravenous corticosteroid therapy or medical rescue therapy

Exclusion Criteria

• Patients with quiescent disease
• Inability to provide informed consent
• Prior colitis related surgery including J-pouch or stoma
• Non-IBD related hospital admission
• Women who are pregnant (from the specimen substudy only)
• Non - English speaking

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
Inpatient ulcerative colitis patients	Standard of care	Patients hospitalized for acute severe ulcerative colitis will be invited to enroll. Participants will be treated at the discretion of their treating physicians per standard of care. We expect some participants will be treated with standard versus accelerated infliximab dosing, permitting comparison, in addition to other treatment strategies.

Primary Outcome Measures

Name	Time	Method
Inpatient response to medical management	In-hospital (approximately 1-2 weeks)	Response assessed by the following clinical care decisions based on binary outcomes: need for more than 1 dose of infliximab (yes=1 or no=0), switch in medical therapies (yes=1 or no=0), and need for surgery (yes=1 or no=0)

Secondary Outcome Measures

Name	Time	Method
Long-term response to medical management	12 months	Response assessed by the following clinical care decisions based on binary outcomes: need for accelerated dosing of infliximab as defined by high-dose (10mg/kg) or more than 3 doses over the first 6 weeks of therapy (yes=1 or no=0), switch in medical therapies (yes=1 or no=0), and need for surgery (yes=1 or no=0)

Trial Locations

Locations (1)

Joanna Melia; 🇺🇸 Baltimore, Maryland, United States