Sonographic Assessment in Severe Ulcerative Colitis Patients Admitted for Intravenous Corticosteroids and Eligible for Infliximab Rescue Therapy; a Prospective Clinician-blinded Observational Study Protocol.

NCT03942861 | Unknown DMC

• 1 other identifier: CopenhagenUHH
• Study Type: observational
• Target: 50
• Locations: 1 country
• Sites: 1

Brief Summary

Introduction Acute severe ulcerative colitis (ASUC) occurs in 15-25 % of all ulcerative colitis (UC) patients. Initial treatment with intravenous corticosteroids fails in 30-50 % of patients, for whom the next line of treatment is biological therapy or colectomy. Acute colectomy has a higher risk of morbidity and mortality than a scheduled colectomy. Data suggest that an accelerated administration of biological treatment in corticosteroid non-responders compared to clinical practice, 5-7 days with intravenous corticosteroids, may be superior in inducing disease remission, thus potentially avoiding acute colectomy. However, there are currently no patient friendly and objective diagnostic tool to preselect patients for such a treatment. The aim of this study is to examine if gastrointestinal ultrasound (GIUS) could preselect corticosteroid non-responders to biological treatment after 48 hours to increase effectiveness of the second line therapy and thereby reduce the morbidity and mortality of ASUC. Methods and analysis The study is a clinician blinded observational multi-center study derived from the Department of Gastroenterology, Herlev Hospital, Denmark. Fifty ASUC patients will be included at the time of hospitalization and followed for 12 months. Baseline clinical activity scores, endoscopic scores, blood samples, fecal-calprotectin, vital parameters and GIUS measurements will be obtained prior to administration of intravenous corticosteroids. All examinations except fecal-calprotectin and endoscopy will be repeated at 48 ± 24 hours, 5-7 days and 3 months after treatment start. Endoscopic scores and fecal-calprotectin will be obtained after 3 months and an additional fecal-calprotectin after 6 ± 1 days. Treatment outcome will be registered at each event and after 12 months. Patients will be divided into corticosteroid responders and non-responders and compared to GIUS measurements at each event using non-parametric statistics (Mann-Whitney and Wilcoxon test) and time to endpoints by survival statistics (Kaplan Meier). ROC statistics will determine the best cutoff values for GIUS parameters for optimal sensitivity, specificity and accuracy. Ethics and dissemination The study is approved by the National committee on health research ethics (H-18031264). Results will be published in relevant scientific journals and presented at international conferences. Fully anonymized data will be accessible from authors upon request.

Conditions

Ulcerative Colitis; Ultrasound Therapy; Complications

Keywords

Ultrasonography; Sonography; Ulcerative Colitis; Inflammatory Bowel Disease; Severe Ulcerative colitis; Treatment response; Monitoring treatment

Outcome Measures

Primary Outcomes (1)

• Changes in GIUS parameters 48 hours after intravenous corticosteroid treatment.

  Number of patients stratified by treatment response (defined by a decrease in clinical Mayo score from baseline ≥ 30 % and ≥ 3 points, along with either a rectal bleeding subscore of 0 or 1 or a decrease in rectal subscore ≥ 1 point) and non-response and their respective change in GIUS parameters (BWT, modified Limberg score, echostratification, inflammatory mesenteric fat and haustration) at 48 ± 24 hours after corticosteroid treatment compared to baseline.

  The outcome measure will be assessed after 18 months and reported within 36 months.

Secondary Outcomes (7)

• Changes in GIUS parameters ability to predict treatment outcome.

  The outcome measure will be assessed after 18 months and reported within 36 months.

• Interrater variability compared to central reading with regards to GIUS parameters.

  The outcome measure will be assessed after 18 months and reported within 36 months.

• Time since last meal correlated to feasibility of GIUS.

  The outcome measure will be assessed after 18 months and reported within 36 months.

• GIUS disease extent assessment compared to endoscopy and CT (if present).

  The outcome measure will be assessed after 18 months and reported within 36 months.

• Calculate the best cutoff value for GIUS parameters for optimal sensitivity, specificity and accuracy compared to treatment outcome and endoscopy results.

  The outcome measure will be assessed after 18 months and reported within 36 months.

Study Arms (1)

Severe Ulcerative Colitis

Consecutive patients admitted as in-patients to the Department of Gastroenterology at four University Hospitals in Denmark, with acute severe UC defined as an affirmed diagnosis of UC according to well established criteria, combined with a Mayo score of 8 or more (i.e. severe disease activity) and the need for intravenous corticosteroid treatment will be screened for participation in the study after informed consent.

Drug: Solu-Medrol

Interventions

Solu-Medrol DRUG

Standard treatment according to Danish Guidelines for acute severe ulcerative colitis.

Severe Ulcerative Colitis

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Consecutive patients admitted as in-patients to the Department of Gastroenterology at four University Hospitals in Denmark, with ASUC defined as an affirmed diagnosis of UC according to well established criteria, combined with a Mayo score of 8 or more (i.e. severe disease activity) and the need for intravenous corticosteroid treatment will be screened for participation in the study after informed consent.

You may qualify if:

• Definitive diagnoses of Ulcerative colitis.
• Mayo clinical score ≥8.
• Need for Hospitalization and intravenous corticosteroid treatment.
• Age between 18-70.
• Ability and willingness to give written consent and comply with study protocol.

You may not qualify if:

• Contraindicators for infliximab.
• Bowel infection.
• Crohn's disease.
• Ultrasonographic inflammation in terminal ileum other than backwash ileitis.
• Bowel wall thickness \<3 in Sigmoid colon.
• Minors.
• Known malignant disease.
• Pregnancy.
• Immune modulating therapy at admission apart from corticosteroids, mesalazine or azathioprine.
• Contraindicators = Patients suffering from moderate to severe heart failure, hypersensitivity to murine proteins, severe bacterial infection.

Sponsors & Collaborators

• Copenhagen University Hospital at Herlev: lead

Study Sites (1)

Herlev University Hospital

Copenhagen, Herlev, 2730, Denmark

RECRUITING

MeSH Terms

Conditions

Colitis, Ulcerative; Inflammatory Bowel Diseases

Interventions

Methylprednisolone Hemisuccinate

Condition Hierarchy (Ancestors)

Colitis; Gastroenteritis; Gastrointestinal Diseases; Digestive System Diseases; Colonic Diseases; Intestinal Diseases

Intervention Hierarchy (Ancestors)

Methylprednisolone; Prednisolone; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds

Study Officials

• Jakob B. Seidelin, MD, PhD

  Copenhagen University Hospital at Herlev

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Johan F.K. Fremberg Ilvemark, MD

CONTACT

0045 38686678; jfre0079@regionh.dk

Jakob B. Seidelin, MD, PhD

CONTACT

0045 38686054; jakob.benedict.seidelin@regionh.dk

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD, Principal Investigator

Study Record Dates

• First Submitted: April 25, 2019
• First Posted: May 8, 2019
• Study Start: February 21, 2019
• Primary Completion: September 21, 2021
• Study Completion: February 21, 2022
• Last Updated: January 27, 2021

Record last verified: 2021-01

Locations

DK (1)