Endovenous Corticosteroid Pulses in Moderate Ulcerative Colitis
- Registration Number
- NCT02921555
- Lead Sponsor
- Grupo Espanol de Trabajo en Enfermedad de Crohn y Colitis Ulcerosa
- 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.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 75
- 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
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description prednisone Prednisone A decreasing conventional course of oral prednisone methylprednisolone & prednisone Prednisone Intravenous bolus of methylprednisolone followed by a decreasing conventional course of oral prednisone methylprednisolone & prednisone Methylprednisolone Intravenous bolus of methylprednisolone followed by a decreasing conventional course of oral prednisone
- Primary Outcome Measures
Name Time Method Percentage of Participants With Endoscopic and Clincal Remission Change from baseline at week 8 The percentage of patients with steroid-free, endoscopic remission, with no rescue therapies.
It has been measured by Mayo endoscopic subscore (MES). MES= 0 (no friability and granularity and intact vascular pattern). MES= 1 (mild erythema or decreased vascular pattern). MES= 2 (marked erythema, absent vascular pattern, friability, and erosions). MES= 3 (spontaneous bleeding and ulceration)Percentage of Participants With Endoscopic and Clinical Remission Change from baseline at week 54 The proportions of patients with steroid-free, endoscopic remission, with no rescue therapies.
It has been measured by Mayo endoscopic subscore (MES). MES= 0 (no friability and granularity and intact vascular pattern). MES= 1 (mild erythema or decreased vascular pattern). MES= 2 (marked erythema, absent vascular pattern, friability, and erosions). MES= 3 (spontaneous bleeding and ulceration)
- Secondary Outcome Measures
Name Time Method Percentage of Patients With Clinical Remission Change from baseline at week 8. It was measured as a decrease in the Mayo index score from baseline of at least 3 points; and a decrease of at least 30% in the rectal bleeding variable of at least 1 point or with an absolute value of 0 or 1.
The Mayo index score is composed of four parts: rectal bleeding, stool frequency, physician assessment, and endoscopy appearance. Each part is rated from 0 to 3, giving a total score of 0 to 12. A score of 3 to 5 points indicates mildly active disease, a score of 6 to 10 points indicates moderately active disease, and a score of 11 to 12 points indicates severely active disease.Number of Participants With Adverse Events 12 months Adverse events (AEs) were collected during the study, from informed consent until the last visit.
Number of Participants With Serious Adverse Events 12 months Serious Adverse Events (SAEs) were defined as any adverse event or adverse drug reaction that resulted in death, is life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability or incapacity, or caused a congenital anomaly/birth defect.
Levels of C-reactive Protein Baseline Clinical assessments included the analytical laboratory test. Blood samples were taken for haematology, and C-reactive protein (mg/L) levels were measured.
Levels of Serum Albumin Baseline Clinical assessments included the analytical laboratory test. Blood samples were taken for haematology, and Serum albumin determination.
Levels of Faecal Calprotectin Baseline Faecal samples were collected at baseline, frozen and stored at -20 Celsius degrees (ºC) for central measurement of faecal calprotectin (FC).
Trial Locations
- Locations (29)
Hospital Universitario Central de Asturias
🇪🇸Oviedo, Astúrias, Spain
Complejo Hospitalario Universitario Santiago de Compostela
🇪🇸Santiago de Compostela, A Coruña, Spain
Hospital de Galdakao
🇪🇸Galdakao, Bilbao, Spain
Hospital Universitario de Ourense
🇪🇸Orense, Ourense, Spain
Hospital Universitario Marqués de Valdecilla
🇪🇸Santander, Cantabria, Spain
Hospital Universitario Cruces
🇪🇸Baracaldo, Vizcaya, Spain
Hospital del Mar
🇪🇸Barcelona, Spain
Hospital General Universitario de Alicante
🇪🇸Alicante, Spain
Hospital Universitario Reina Sofia
🇪🇸Córdoba, Spain
Hospital Universitari Dr. Josep Trueta
🇪🇸Girona, Spain
Hospital de la Santa Creu i Sant Pau
🇪🇸Barcelona, Spain
Hospital De La Princesa
🇪🇸Madrid, Spain
Hospital Universitario La Paz
🇪🇸Madrid, Spain
Hospital Gregorio Marañon
🇪🇸Madrid, Spain
Hospital 12 de Octubre
🇪🇸Madrid, Spain
Hospital Universitario Ramon y Cajal
🇪🇸Madrid, Spain
Mútua de Terrassa
🇪🇸Terrassa, Spain
Hospital Universitario General de Valencia
🇪🇸Valencia, Spain
Hospital Clínico de Valencia
🇪🇸Valencia, Spain
Hospital de Manises
🇪🇸Valencia, Spain
Hospital Universitario Río Hortega
🇪🇸Valladolid, Spain
Hospital Universitari La Fe
🇪🇸Valencia, Spain
hospital Puerta de Hierro-Majadahonda
🇪🇸Majadahonda, Madrid, 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
Hospital Germans Trias i Pujol
🇪🇸Badalona, Barcelona, Spain
Consorci Hospitalari de Terrassa
🇪🇸Terrassa, Barcelona, Spain
Hospital Álvaro Cunqueiro
🇪🇸Vigo, Pontevedra, Spain