Care Path for the Management of Ulcerative Colitis

Study Overview
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Brief Summary
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Assess if standardized care-path that features objective evaluations of disease activity and time-bound algorithms is superior to usual step-care in the treatment of ulcerative colitis.

Detailed Description
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Step-care based on symptomatic response remains the overwhelming algorithm of choice in clinical practice. Many subjects receive infliximab only as a last resort, when the subject is very ill and has failed repeated attempts of corticosteroid induction therapy. Although this situation is far from ideal, to change such entrenched physician behavior will require compelling evidence that Step-care results in inferior outcomes to earlier introduction of effective therapy. Based on these considerations, we will perform a cluster randomization trial in which 40 gastroenterology practices will be randomly assigned to a treatment algorithm featuring the early use of combination therapy, treatment intensification guided by objective assessments of inflammation and the use of remission as a therapeutic goal or a conventional Step-care approach.

Official Title
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A Cluster Randomized Controlled Trial of a Care-Path for the Management of Ulcerative Colitis

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Other: Enhanced treatment algorithm
* Other: Usual Care


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Females of child bearing potential must have a negative serum pregnancy test prior to randomization, and must use a hormonal (oral, implantable or injectable) or barrier method of birth control throughout the study. Females unable to bear children must have documentation of such in the source records -- - Documented diagnosis of UC with a Mayo Clinic Score (MCS) ≥6 and a baseline Mayo Endoscopy Score >2. Either an elevated serum C-reactive protein (CRP) (above the Upper Level of Normal (ULN) according to local laboratory results) or elevated fecal calprotectin (> 250 mg/kg) concentration. Requires sigmoidoscopic evaluation at baseline (standard of care) Written informed consent must be obtained and documented. Ability of subject to participate fully in all aspects of this clinical trial in the opinion of the investigator. Exclusion Criteria: Previous failure of TNF antagonist therapy Received any investigational drug in the past 30 days or 5 half-lives, whichever is longer. Pregnant or lactating women. Any conditions (e.g., history of alcohol or substance abuse) which in the opinion of the investigator, may interfere with the subject's ability to comply with study procedures.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Enhanced treatment algorithm<br>Treatment algorithm featuring the early use of combination therapy, treatment intensification guided by objective assessments of inflammation and the use of remission as a therapeutic goal | Other: Enhanced treatment algorithm<br>* Practitioners assigned to the intervention arm will be educated on the use of the Enhanced Algorithm.<br>|
| Placebo Comparator: Usual Care<br>These subjects will be managed according to local treatment guidelines for the treatment of UC. | Other: Usual Care<br>* usual step care practice<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients in remission at the end of 12 months. | Remission is defined as 1) a Mayo Clinic Score of ≤2 with rectal bleeding and stool frequency sub-scale scores of 0) with no use of corticosteroids, and 3) normalization of the subject's index inflammatory marker (c-reactive protein or calprotectin). The primary endpoint will be assessed at Month 12. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Proportion of patients in remission over the course of the study | The time in remission over the course of the study; occurrence of surgery or hospitalization for Ulcerative Colitis; occurrence of disease-related complications; health related QoL (Short-Form 36 questionnaire [SF-36] and EuroQoL instrument [EQ-5D]); and, subject | 18 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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CONSTRUCT, Cluster randomization controlled trial, Gastroenterology practices in North America