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

NCT ID: NCT02665845

Last Updated: 2021-08-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 160 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2016-06-13
• Study Completion Date: 2021-05-11

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.

Conditions

Ulcerative Colitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

5-ASA group

Patients will receive corticosteroids with optimized 5-ASA.

Group Type: EXPERIMENTAL

5-ASA

Intervention Type: DRUG

5ASA treatment (oral 5ASA will be given to all patients in this arm, in addition to topical 5ASA in patients who tolerate it).

Corticosteroids

Intervention Type: DRUG

Corticosteroids will be given to all patients.

Control group

Patients will receive corticosteroids alone.

Group Type: ACTIVE_COMPARATOR

Corticosteroids

Intervention Type: DRUG

Corticosteroids will be given to all patients.

Interventions

5-ASA

5ASA treatment (oral 5ASA will be given to all patients in this arm, in addition to topical 5ASA in patients who tolerate it).

Intervention Type: DRUG

Corticosteroids

Corticosteroids will be given to all patients.

Intervention Type: DRUG

Other Intervention Names

5-aminosalicylates; Usual care

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Centre Hospitalier Universitaire de Saint Etienne

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

ROBLIN Xavier, MD

Role: PRINCIPAL_INVESTIGATOR

CHU SAINT-ETIENNE

Locations

Chu Saint Etienne

Saint-Etienne, , France

Department of Gastroenterology Venizeleio General Hospital, Leoforos Knosou

Heraklion, , Greece

Sheba Medical Center

Tel Litwinsky, Ramat-Gan, Israel

Università di Roma Sapienza

Rome, , Italy

Zvezdara University Clinical Center, Gastroenterology Department

Belgrade, , Serbia

Institute of Gastroenterology and Department of Internal Medicine, Yonsei University College of Medicine

Seoul, , South Korea

Countries

France; Greece; Israel; Italy; Serbia; South Korea

Other Identifiers

2015-002671-21

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

1508090

Identifier Type: -

Identifier Source: org_study_id