Endovenous Corticosteroid Pulses in Moderate Ulcerative Colitis

NCT ID: NCT02921555

Last Updated: 2025-02-21

Basic Information

• Recruitment Status: TERMINATED
• Clinical Phase: PHASE4
• Total Enrollment: 75 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-10-11
• Study Completion Date: 2022-11-07

Brief Summary

The purpose of this study is to determine the efficacy of high-dose corticosteroid pulses added to conventional oral corticosteroid course for moderate flares of ulcerative colitis.

Detailed Description

Oral corticosteroids (CS) are the treatment of choice for moderate flares of ulcerative colitis (UC) in patients who are on 5-aminosalicylic acid (5ASA) maintenance therapy. However, the efficacy of oral CS is limited, with up to 50% of remission rate in the available randomized controlled trials (RCTs). By the other hand, uncompleted disease remission after CS use, that is, clinical but not endoscopic remission, has been associated with a higher risk of hospitalizations and need for immunomodulator or colectomy in UC. Uncontrolled data suggests that intravenous CS (IV CS) may increase the remission rate and also reduce the proportion of patients developing steroid-dependency after the index course of CS.

The hypothesis of this study is that the addition of a 3-day high-dose IV CS pulses schedule administered in the outpatient infusion unit, added to a conventional oral CS course increases the endoscopic remission rate and reduces the 1-year proportion of patients developing steroid-dependency.

This is a randomized, phase IV, open-label, multicenter, controlled study.

The planned number of patients to be included is 148, distributed in two treatment arms (with or without initial high-dose CS pulse), and stratified regarding disease onset and mesalazine use.

The main end-point will be the proportion of patients with steroid-free, clinical and endoscopic remission at 8 and 54 weeks, with no rescue therapies.

The demonstration of a higher efficacy of the proposed treatment schedule would impact on a lower requirement for conventional immunosuppressive therapy (thiopurines) and biological agents, reduced hospitalizations and surgery. Moreover, this treatment regimen allows an outpatient management of moderate flares.

Baseline characteristics will be analyzed by descriptive statistical analysis by conventional methods. Categorical variables will be compared using Mann-Whitney test and continuous variables by Student T test.

In order to evaluate the primary endpoint a Chi square test will be performed to compare the proportions of patients in both study groups that achieved clinical and endoscopic steroid-free remission at 8 weeks and is maintained without steroids or salvage therapy and with no rescue therapy up to 54 weeks.

Per protocol (PP) and intention-to-treat (IT) analysis will be made The Per Protocol analysis will include all participants who did adequately adhere to the protocol, in particular those who did received the total amount of the intervention.

Missing outcomes data will be treated as non-response imputation (NRI). The intention-to treat-analysis will only include all randomized patients in the analysis, all retained in the group to which they were allocated, except those patients with missing outcomes that did not completed treatment regimen due to SAE criteria or treatment failure.

In order to evaluate the secondary endpoints a Chi square test and a Student T test will be performed for both study groups.

Cumulative probabilities of relapse, steroid dependency and surgery will be evaluated in both groups by Kaplan-Meiery, and compared by using log-rank test.

Finally, association analysis of early clinical response, clinical and endoscopic remission at week 8 and week 8 and 54 will be performed by chi-square test and Student T test; those variables that reach a Pvalue ≤ 0.1 will be included in the logistic regression analysis.

Conditions

Ulcerative Colitis

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: OTHER
• Blinding Strategy: NONE

Study Groups

methylprednisolone & prednisone

Intravenous bolus of methylprednisolone followed by a decreasing conventional course of oral prednisone

Group Type: EXPERIMENTAL

Methylprednisolone

Intervention Type: DRUG

Intravenous bolus of methylprednisolone 0.5g/day for 3 consecutive days followed by a decreasing conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)

Prednisone

Intervention Type: DRUG

Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)

prednisone

A decreasing conventional course of oral prednisone

Group Type: ACTIVE_COMPARATOR

Prednisone

Intervention Type: DRUG

Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)

Interventions

Methylprednisolone

Intravenous bolus of methylprednisolone 0.5g/day for 3 consecutive days followed by a decreasing conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)

Intervention Type: DRUG

Prednisone

Conventional course of oral prednisone (week1; 60mg/d, w2; 50mg/d, w3;40mg/d, w4; 30mg/d, w5; 20mg/d, w6; 15mg/d, w7; 10mg/d, w8; 5 mg/d, w9; 0mg/d)

Intervention Type: DRUG

Other Intervention Names

Urbason; URbason

Eligibility Criteria

Inclusion Criteria

• Ulcerative colitis diagnosis by Lennard-Jones criteria
• ≥18 years
• Left or extended extent of disease
• Moderate flares of ulcerative colitis according to disease activity index (DAI)
• No maintenance therapy or 5ASA treatment
• The patient is available to understand study procedures and to sign the inform consent form
• Inform Consent Form

Exclusion Criteria

• Previous or current thiopurines, methotrexate or biological treatment
• Administration of systemic corticoids the last 6 months
• Acute or moderate systemic infection
• Diabetes mellitus or arterial hypertension
• Pregnancy or breastfeeding
• Allergic reactions associated to corticosteroids therapy

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

Sponsors

Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Eugeni Domènech, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa

Locations

Complejo Hospitalario Universitario Santiago de Compostela

Santiago de Compostela, A Coruña, Spain

Hospital Germans Trias i Pujol

Badalona, Barcelona, Spain

Althaia, xarxa assistencial universitaria de Manresa

Manresa, Barcelona, Spain

Consorci Corporació Sanitària Parc Taulí

Sabadell, Barcelona, Spain

Hospital Moisès Broggi

Sant Joan Despí, Barcelona, Spain

Consorci Hospitalari de Terrassa

Terrassa, Barcelona, Spain

Hospital de Galdakao

Galdakao, Bilbao, Spain

Hospital Universitario Marqués de Valdecilla

Santander, Cantabria, Spain

hospital Puerta de Hierro-Majadahonda

Majadahonda, Madrid, Spain

Hospital Universitario de Ourense

Ourense, Ourense, Spain

Hospital Álvaro Cunqueiro

Vigo, Pontevedra, Spain

Hospital Universitario Central de Asturias

Oviedo, Principality of Asturias, Spain

Hospital Universitario Cruces

Barakaldo, Vizcaya, Spain

Hospital General Universitario de Alicante

Alicante, , Spain

Hospital de la Santa Creu i Sant Pau

Barcelona, , Spain

Hospital del Mar

Barcelona, , Spain

Hospital Universitario Reina Sofia

Córdoba, , Spain

Hospital Universitari Dr. Josep Trueta

Girona, , Spain

Hospital De La Princesa

Madrid, , Spain

Hospital Gregorio Marañon

Madrid, , Spain

Hospital Universitario La Paz

Madrid, , Spain

Hospital 12 de Octubre

Madrid, , Spain

Hospital Universitario Ramon y Cajal

Madrid, , Spain

Mútua de Terrassa

Terrassa, , Spain

Hospital Clínico de Valencia

Valencia, , Spain

Hospital Universitario General de Valencia

Valencia, , Spain

Hospital de Manises

Valencia, , Spain

Hospital Universitari La Fe

Valencia, , Spain

Hospital Universitario Río Hortega

Valladolid, , Spain

Countries

Spain

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Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

CECUM

Identifier Type: -

Identifier Source: org_study_id