Clinical trial NCT02921555: Endovenous Corticosteroid Pulses in Moderate Ulcerative Colitis
Official title: Efficacy of High-dose Corticosteroid Pulses Added to Conventional Oral Corticosteroid Course for Moderate Flares of Ulcerative Colitis.
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE4
Conditions: Ulcerative Colitis
Keywords: RCT (randomized controlled trial)
Lead sponsor: Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa
Sponsor class: OTHER
First posted: 2016-10-03
Enrollment: 75
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.

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

Primary outcomes:
measure: Percentage of Participants With Endoscopic and Clincal Remission
timeFrame: Change from baseline at week 8
measure: Percentage of Participants With Endoscopic and Clinical Remission
timeFrame: Change from baseline at week 54
Secondary outcomes:
measure: Percentage of Patients With Clinical Remission
timeFrame: Change from baseline at week 8.
measure: Number of Participants With Adverse Events
timeFrame: 12 months
measure: Number of Participants With Serious Adverse Events
timeFrame: 12 months
measure: Levels of C-reactive Protein
timeFrame: Baseline
measure: Levels of Serum Albumin
timeFrame: Baseline
measure: Levels of Faecal Calprotectin
timeFrame: Baseline
Other outcomes:
Locations:
city: Santiago de Compostela
country: Spain
facility: Complejo Hospitalario Universitario Santiago de Compostela
state: A Coruña
city: Oviedo
country: Spain
facility: Hospital Universitario Central de Asturias
state: Astúrias
city: Badalona
country: Spain
facility: Hospital Germans Trias i Pujol
state: Barcelona
city: Manresa
country: Spain
facility: Althaia, xarxa assistencial universitaria de Manresa
state: Barcelona
city: Sabadell
country: Spain
facility: Consorci Corporació Sanitària Parc Taulí
state: Barcelona
city: Sant Joan Despí
country: Spain
facility: Hospital Moisès Broggi
state: Barcelona
city: Terrassa
country: Spain
facility: Consorci Hospitalari de Terrassa
state: Barcelona
city: Galdakao
country: Spain
facility: Hospital de Galdakao
state: Bilbao
city: Santander
country: Spain
facility: Hospital Universitario Marqués de Valdecilla
state: Cantabria
city: Majadahonda
country: Spain
facility: hospital Puerta de Hierro-Majadahonda
state: Madrid
city: Orense
country: Spain
facility: Hospital Universitario de Ourense
state: Ourense
city: Vigo
country: Spain
facility: Hospital Álvaro Cunqueiro
state: Pontevedra
city: Baracaldo
country: Spain
facility: Hospital Universitario Cruces
state: Vizcaya
city: Alicante
country: Spain
facility: Hospital General Universitario de Alicante
city: Barcelona
country: Spain
facility: Hospital de la Santa Creu i Sant Pau
city: Barcelona
country: Spain
facility: Hospital del Mar
city: Córdoba
country: Spain
facility: Hospital Universitario Reina Sofia
city: Girona
country: Spain
facility: Hospital Universitari Dr. Josep Trueta
city: Madrid
country: Spain
facility: Hospital De La Princesa
city: Madrid
country: Spain
facility: Hospital Gregorio Marañon
city: Madrid
country: Spain
facility: Hospital Universitario La Paz
city: Madrid
country: Spain
facility: Hospital 12 de Octubre
city: Madrid
country: Spain
facility: Hospital Universitario Ramon y Cajal
city: Terrassa
country: Spain
facility: Mútua de Terrassa
city: Valencia
country: Spain
facility: Hospital Clínico de Valencia
city: Valencia
country: Spain
facility: Hospital Universitario General de Valencia
city: Valencia
country: Spain
facility: Hospital de Manises
city: Valencia
country: Spain
facility: Hospital Universitari La Fe
city: Valladolid
country: Spain
facility: Hospital Universitario Río Hortega
Study officials:
affiliation: Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa
name: Eugeni Domènech, MD, PhD
role: PRINCIPAL_INVESTIGATOR
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