Combination Corticosteroids+5-aminosalicylic Acids Compared to Corticosteroids Alone (for Ulcerative Colitis).

Study Overview
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Brief Summary
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The role of steroids in the treatment of severe ulcerative colitis (UC) exacerbation is well established and recommended by professional societies. Similarly, 5-aminosalycilates (5-ASA) agents in the form of mesalamine/mesalzine are well established proven therapy in mild-moderate UC, and the combination of oral 5-ASA with topical (per-rectal enema) 5-ASA was shown to be superior to oral 5ASA alone in patients with mild moderate UC. Thus, in most cases, when a patient with UC experiences a flare while taking 5-ASA therapy, treatment is usually optimized by maximizing the oral dose to 4gr/day and adding topical therapy until the flare is controlled. If this is unhelpful, or if the flare is severe to begin with, corticosteroids are usually prescribed. However, there are very scarce data comparing steroids versus 5-ASA in the treatment of severe UC exacerbation. The aim of this study is to compare the efficacy of steroids alone vs. combination of steroids + 5-ASA in the treatment of moderate-severe UC exacerbation.

Detailed Description
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The role of steroids in the treatment of severe ulcerative colitis (UC) exacerbation is well established and recommended by professional societies. This recommendation is based on pivotal studies carried 50-60 years ago, by Truelove &Witts. Similarly, 5-aminosalycilates (5-ASA) agents in the form of mesalamine/mesalzine are well established proven therapy in mild-moderate UC, and the combination of oral 5-ASA with topical (per-rectal enema) 5-ASA was shown to be superior to oral 5ASA alone in patients with mild moderate UC. Thus, in most cases, when a patient with UC experiences a flare while taking 5-ASA therapy, treatment is usually optimized by maximizing the oral dose to 4gr/day and adding topical therapy until the flare is controlled. If this is unhelpful, or if the flare is severe to begin with, corticosteroids are usually prescribed. However, there are very scarce data comparing steroids versus 5-ASA in the treatment of severe UC exacerbation. In 1962 truelove et al compared topical and systemic corticosteroid therapy with sulphasalazine, and found steroids to be superior to sulfasalazine. Importantly, there are no data investigating whether the addition and/or continuation of 5-ASA agents as combination therapy with systemic corticosteroids is superior to corticosteroids alone in patients with moderate-severe active UC. This knowledge gap is pronounced in patients admitted to the hospital for intravenous corticosteroid treatment with moderate severe UC flare, in whom it is currently unknown if the addition of 5-ASA (Oral and/or topical) to corticosteroids will confer additional benefit and improve patients outcomes. Thus, in practical terms, the decision whether to stop or continue 5-ASA treatment or whether to add 5-ASA to steroids in the treatment of moderate-severe UC exacerbation is taken on an arbitrary basis. This is important shortcoming and knowledge gap in current medicine, as patients admitted with moderate-severe UC flare who do not respond to corticosteroids and require salvage therapy with infliximab, cyclosporine, or even urgent colectomy. This makes it prudent to explore any avenue for possible improvement of response to corticosteroids in this setting, for instance by addition of 5ASA. The aim of this study is: To compare the efficacy of steroids alone vs. combination of steroids + 5-ASA in the treatment of moderate- severe UC exacerbation.

Official Title
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Combination Corticosteroids+5-aminosalicylic Acids Compared to Corticosteroids Alone in the Treatment of Moderate-severe Active Ulcerative Colitis: A Protocol of a Multi-center Prospective Randomized Investigator Blinded Trial.

Conditions
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Ulcerative Colitis

Intervention / Treatment
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* Drug: 5-ASA
* Drug: Corticosteroids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: UC known and diagnosed by established clinical-endoscopic and histological criteria or newly-diagnosed UC, based on clinical and endoscopic findings, and about to start treatment with corticosteroids. Current hospitalization with Severe UC exacerbation as defined by a Lichtiger score of >10 Age >18 Has not been on oral systemic corticosteroids more than 14 days prior to hospitalization If taking a thiopurine, the dose need to be stable for the last 2 months before admission Exclusion Criteria: Pregnant women Allergy / unable to take prednisone / hydrocortisone/ 5-ASA. Active infection - either enteric or elsewhere Severe renal, liver or cardio respiratory comorbidity Toxic megacolon, or clinical features suggestive of a need for imminent colectomy Treatment with an anti-TNF within the prior 3 months Prior treatment with cyclosporine or tacrolimus within the prior 3 months Alcohol dependency Unable or unwilling to provide informed consent Participating in other clinical trial within the 2 months prior to admission

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: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 5-ASA group<br>Patients will receive corticosteroids with optimized 5-ASA. | Drug: 5-ASA<br>* 5ASA treatment (oral 5ASA will be given to all patients in this arm, in addition to topical 5ASA in patients who tolerate it).<br>* Other names: 5-aminosalicylates;Drug: Corticosteroids<br>* Corticosteroids will be given to all patients.<br>* Other names: Usual care;|
| Active Comparator: Control group<br>Patients will receive corticosteroids alone. | Drug: Corticosteroids<br>* Corticosteroids will be given to all patients.<br>* Other names: Usual care;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients who respond to the treatment by day 7. | The primary endpoint will be the percentage of patients who respond to the treatment by day 7. Response will be defined by a drop of >3 points in the lichtiger score and an absolute score <10 on the two prior consecutive days without the need for rescue medications or surgery. In patients who improve and are discharged prior to day 7, the lichtiger score will be calculated based on the two last days of hospitalization, provided that at least 3 days of study medications were dispensed. Patients discharged before 3 days of study medications have been administered will be considered in-eligible and will be dropped out of the analyses. | Day 7 |