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

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ClinicalTrials.gov Identifier: NCT03942861
Recruitment Status : Recruiting
First Posted : May 8, 2019
Last Update Posted : May 8, 2019
Sponsor:
Information provided by (Responsible Party):
Johan F. Ilvemark, Copenhagen University Hospital at Herlev

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.


Condition or disease Intervention/treatment
Ulcerative Colitis Ultrasound Therapy; Complications Drug: Solu-Medrol

  Show Detailed Description

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Study Type : Observational
Estimated Enrollment : 50 participants
Observational Model: Cohort
Time Perspective: Prospective
Official Title: Sonographic Assessment in Severe Ulcerative Colitis Patients Admitted for Intravenous Corticosteroids and Eligible for Infliximab Rescue Therapy; a Prospective Clinician-blinded Observational Study Protocol.
Actual Study Start Date : February 21, 2019
Estimated Primary Completion Date : August 21, 2020
Estimated Study Completion Date : February 21, 2022

Resource links provided by the National Library of Medicine

Drug Information available for: Infliximab

Group/Cohort Intervention/treatment
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
Standard treatment according to Danish Guidelines for acute severe ulcerative colitis.




Primary Outcome Measures :
  1. Changes in GIUS parameters 48 hours after intravenous corticosteroid treatment. [ Time Frame: The outcome measure will be assessed after 18 months and reported within 36 months. ]
    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.


Secondary Outcome Measures :
  1. Changes in GIUS parameters ability to predict treatment outcome. [ Time Frame: The outcome measure will be assessed after 18 months and reported within 36 months. ]
    Number of patients stratified after treatment response and non-response after 6 ± 1 days, within 3 months and after 12 months compared to changes in GIUS parameters at each event compared to baseline.

  2. Interrater variability compared to central reading with regards to GIUS parameters. [ Time Frame: The outcome measure will be assessed after 18 months and reported within 36 months. ]
    All GIUS scans will be performed by a trained GIUS gastroenterologist and proof read by a second specialist. We wish to examine eventual differences between their assessments.

  3. Time since last meal correlated to feasibility of GIUS. [ Time Frame: The outcome measure will be assessed after 18 months and reported within 36 months. ]
    Although some studies suggest 4 hours of fasting to diminish peristalsis and intraluminal air, fasting before examination is generally not necessary, making it preparation free. We will register patients time since last meal and correlate it to feasibility of GIUS.

  4. GIUS disease extent assessment compared to endoscopy and CT (if present). [ Time Frame: The outcome measure will be assessed after 18 months and reported within 36 months. ]
    Number of correct GIUS assessment of inflammatory extension compared to endoscopy and CT (if present), which is seen as the golden standard, defined by location (rectum, sigmoid colon, descending colon, transverse colon, ascending colon and terminale ileum.

  5. Calculate the best cutoff value for GIUS parameters for optimal sensitivity, specificity and accuracy compared to treatment outcome and endoscopy results. [ Time Frame: The outcome measure will be assessed after 18 months and reported within 36 months. ]
    ROC analyses will be performed to determine the best cutoff values for GIUS parameters for optimal sensitivity, specificity and accuracy in predicting treatment outcome (responder vs. non-responder).

  6. Change in GIUS parameters correlation with change in endoscopic scores and fecal calprotectin within 3 months compared to baseline. [ Time Frame: The outcome measure will be assessed after 18 months and reported within 36 months. ]
    Change in GIUS parameters for steroid responders and non-responders and correlation with change in Mayo endoscopic sub-score, UCEIS and fecal calprotectin within 3 months compared to baseline.

  7. Change in GIUS parameters correlation with change clinical scores and biochemistry on 48 ± 24 hours, 6 ± 1 days and after 3 months compared to baseline. [ Time Frame: The outcome measure will be assessed after 18 months and reported within 36 months. ]
    Change in GIUS parameters for steroid responders and non-responders and correlation with change in Mayo clinical score, SCCAI, CRP, alpha-1-antitrypsin and increase of albumin or hemoglobin on 48 ± 24 hours, 6 ± 1 days and after 3 months compared to baseline.



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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
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.
Criteria

Inclusion Criteria:

  • 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.

Exclusion Criteria:

  • 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.


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03942861


Contacts
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Contact: Johan F.K. Fremberg Ilvemark, MD 0045 38686678 jfre0079@regionh.dk
Contact: Jakob B. Seidelin, MD, PhD 0045 38686054 jakob.benedict.seidelin@regionh.dk

Locations
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Denmark
Herlev University Hospital Recruiting
Copenhagen, Herlev, Denmark, 2730
Contact: Johan F.K. Fremberg Ilvemark, MD    0045 38686678    jfre0079@regionh.dk   
Contact: Jakob B. Seidelin, MD, PhD    0045 38686054    jakob.benedict.seidelin@regionh.dk   
Sponsors and Collaborators
Copenhagen University Hospital at Herlev
Investigators
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Principal Investigator: Jakob B. Seidelin, MD, PhD Copenhagen University Hospital at Herlev

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Responsible Party: Johan F. Ilvemark, MD, Principal Investigator, Copenhagen University Hospital at Herlev
ClinicalTrials.gov Identifier: NCT03942861     History of Changes
Other Study ID Numbers: CopenhagenUHH
First Posted: May 8, 2019    Key Record Dates
Last Update Posted: May 8, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided
Plan Description: Our plan is that fully anonymized data will be accessible from authors upon request.

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Johan F. Ilvemark, Copenhagen University Hospital at Herlev:
Ultrasonography
Sonography
Ulcerative Colitis
Inflammatory Bowel Disease
Severe Ulcerative colitis
Treatment response
Monitoring treatment

Additional relevant MeSH terms:
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Colitis
Ulcer
Colitis, Ulcerative
Gastroenteritis
Gastrointestinal Diseases
Digestive System Diseases
Colonic Diseases
Intestinal Diseases
Pathologic Processes
Inflammatory Bowel Diseases
Infliximab
Methylprednisolone Hemisuccinate
Dermatologic Agents
Gastrointestinal Agents
Antirheumatic Agents
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Neuroprotective Agents
Protective Agents
Antineoplastic Agents, Hormonal
Antineoplastic Agents