Clinical trial NCT02665845: Combination Corticosteroids+5-aminosalicylic Acids Compared to Corticosteroids Alone (for Ulcerative Colitis).
Official title: 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Ulcerative Colitis
Lead sponsor: Centre Hospitalier Universitaire de Saint Etienne
Sponsor class: OTHER
First posted: 2016-01-28
Enrollment: 160
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of patients who respond to the treatment by day 7.
timeFrame: Day 7
Secondary outcomes:
Other outcomes:
Locations:
city: Saint Etienne
country: France
facility: Chu Saint Etienne
city: Heraklion
country: Greece
facility: Department of Gastroenterology Venizeleio General Hospital, Leoforos Knosou
city: Tel HaShomer
country: Israel
facility: Sheba Medical Center
state: Ramat-Gan
city: Rome
country: Italy
facility: Università di Roma Sapienza
city: Seoul
country: Korea, Republic of
facility: Institute of Gastroenterology and Department of Internal Medicine, Yonsei University College of Medicine
city: Belgrade
country: Serbia
facility: Zvezdara University Clinical Center, Gastroenterology Department
Study officials:
affiliation: CHU SAINT-ETIENNE
name: ROBLIN Xavier, MD
role: PRINCIPAL_INVESTIGATOR
References: