Adherence of a 1.600 mg Single Tablet 5-ASA Treatment of Ulcerative Colitis (EASI)

Adherence of a 1.600 mg Single Tablet 5-ASA Treatment of Ulcerative Colitis (EASI-trial)

Several oral mesalazine (5-ASA) formulations exist, but the regimes require several tablets per day. Such regimens are not ideal and can interfere with normal daily activities of patients. Non-adherence has been associated with an increase in the risk of relapse and worse disease course; leading to a decrease in quality of life, an increase in societal and personal costs, and worst case increases the risk of colorectal cancer. Recently, a new formula for 5-ASA has been approved by the Danish Medicine Agency, with a single tablet regime per day.

Primary purpose:

• To investigate whether a simplified treatment regimen for 5- ASA (1600 mg as one tablet per day [intervention]) improves adherence with preserved remission rates compared to conventional therapy.

Secondary purposes:

• Compare levels of endoscopic, mucosal and histological inflammation in predicting risk of relapse between the intervention group and the conventional therapy group.
• Investigate whether a simplified treatment regimen improves the disease course compared to the conventional therapy.
• To assess the correlation between different endpoints and the disease courses, with the use of clinical, endoscopic, histological, self-reported and biochemical markers.
• Improve, correlate and assess patient-reported outcomes in a prospective manner.
• To establish a biobank of cases with quiescent/mild ulcerative colitis (UC) for identification of future biomarkers.

Study Overview

• Status: Recruiting
• Conditions: Ulcerative Colitis
• Intervention / Treatment: Drug: Mesalazine; Drug: Mesalazine

• Study Type: Interventional
• Enrollment (Estimated): 200
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Flemming Bendtsen, MDSci; Phone Number: +45 38623273; Email: Flemming.Bendtsen@regionh.dk
• Study Contact Backup: Name: Bobby Lo, MD; Email: bobby.lo@regionh.dk

Study Locations

• Denmark
  • Hvidovre, Denmark, 2200
    • Recruiting
    • Copenhagen University Hospital Hvidovre
    • Contact: Flemming Bendtsen; Email: Flemming.bendtsen@regionh.dk
    • Contact: Bobby Lo; Phone Number: +4528580410; Email: bobby.lo@regionh.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Signed informed consent
• Age between and including 18 and 60
• Diagnosed with UC according to the Copenhagen Diagnostic Criteria
• Length of disease of max. 10 years
• Stable remission on 5-ASA (defined as partial Mayo score ≤1) for at least 2 months without need for oral corticosteroids before inclusion.
• Endoscopic remission defined as Mayo Clinic Endoscopic Score < 2

• Have had a relapse within the last 2 years

  • Defined as the need of escalation of treatment or change medical treatment.

Exclusion Criteria:

• Evidence of infectious diarrhoea (i.e. pathogenic viruses, bacteria or Clostridium difficile toxin in stool culture) within the last month
• On immunomodulators, including methotrexate
• On any biological therapy
• Any previous abdominal surgery related to UC
• Any chronic infections (e.g. HBV, HCV, HIV)
• Any severe concomitant cardiovascular, autoimmune, hematologic, hepatic, renal, endocrine, oncologic or psychiatric disorder, which in the opinion of the investigator might have an influence on the patient's compliance or the interpretation of the results
• Well-founded doubt about the patient's cooperation, e.g., because of addiction to alcohol or drugs in the opinion of the investigators.
• Participation in another clinical trial within the last 30 days, or simultaneous participation in another clinical trial.
• Any previous documented allergic reaction to tested the medical drugs

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1600 mg Asacol (mesalazine); 1600 mg mesalazine (Asacol) treatment regimen (1 tablet per day) for a year	Drug: Mesalazine; 1600 mg Asacol [mesalazine]; Drug: Mesalazine; 800 mg Asacol [mesalazine]
Active Comparator: 800 mg Asacol (mesalazine); 800 mg mesalazine (Asacol) treatment regimen (3 tablets per day) for a year	Drug: Mesalazine; 1600 mg Asacol [mesalazine]; Drug: Mesalazine; 800 mg Asacol [mesalazine]

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Medical Adherence	Measured by drug accountability log Patients having taken ≥80 % are categorised as adherent	through study completion, an average of 2 year
Medical Adherence	Measured by "Medical adherence rating scale" (MARS) Medical adherence rating scale is a self-reported medical adherence tool consisting of 5 items scored on a 5 point Likert scale (ranging from 5-25). The scale has been used in several IBD studies and a global score > 20 indicates a good adherence.	through study completion, an average of 2 year
Medical Adherence	Measured byf drug accountability log (outcome 1) and "Medical adherence rating scale" (MARS, outcome 2) separately, excl. pregnant and breastfeeding women. Further detail see outcome 1 and 2	through study completion, an average of 2 year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of disease activity by Mayo Score	The Mayo Score is composed of 4 items. A score from 0-2 is categorised as remission and 11-12 as severe.	through study completion, an average of 2 year
Assessment of disease activity by the Simple clinical colitis activity index (SCCAI)	The SCCAI rely solely on clinical assessments. Clinical remission are defined as SCCAI < 1 and clinical response as a change of at least 1 point.	through study completion, an average of 2 year
Assessment of endoscopic severity by the Ulcerative Colitis Endoscopic Index of Severity (UCEIS)	The UCEIS endoscopic severity on a scale of 1-4. Higher score mean worse disease severity.	through study completion, an average of 2 year
Assessment of endoscopic severity by the Mayo endoscopic score	The Mayo endoscopic score is scored on a scale of 0-3. Higher score mean worse disease severity.	through study completion, an average of 2 year
Assessment of histological severity by the Geboes score	The Geboes score is interpreted as such: a higher score means higher disease activity.	through study completion, an average of 2 year
Assessment of histological severity by the Nancy Index	The Nancy Index are interpreted as such: The grade 4 correspond to severe disease, grade 0 as " absence of significant histological disease".	through study completion, an average of 2 year
Assessment of histological severity by the Robarts Histopathology Index (RHI)	The RHI are interpreted as such: The score are ranging between 0 (no disease activity) to 33 (severe disease activity).	through study completion, an average of 2 year
Correlation between the different clinical scores	Comparison, correlation and association between the different endoscopic, histological and disease activity indices. Included will be: Mayo score, Simple clinical colitis activity index (SCCAI), Ulcerative Colitis Endoscopic Index of Severity (UCEIS), Nancy Index, Robarts Histopathology Index (RHI) and the Geboes score (see outcome 4-10).	through study completion, an average of 2 year
Remission - days	Differences in number of days in remission during the trial	through study completion, an average of 2 year
Relapse - days	Differences in number of days in relapse during the trial	through study completion, an average of 2 year
Remission and relapse - episodes	Differences episodes of relapses during the trial	through study completion, an average of 2 year
Changes in quality of life	Prospective analyses of quality of life using 12-Item Short Form Survey (SF12). The SF12 is measured on a global score from 12-56. Beside a global score, a mental and physical dimension will also be calculated.	through study completion, an average of 2 year
Changes in disease specific quality of life	Prospective analyses quality of life using the Short inflammatory bowel disease questionnaire (SIBDQ) The SIBDQ is a quality of life (QOL) questionnaire ranging from 10-70. Higher score means better QOL.	through study completion, an average of 2 year
Changes in disability among ulcerative colitis patients	Prospective analyses of disability using the Inflammatory bowel disease disability index (IBD-DI) The IBD-DI measures the disability among patients with inflammatory bowel disease. Higher scores means worse disability.	through study completion, an average of 2 year
Changes in sleep quality	Prospective analyses of sleep using the Pittsburgh Sleep Quality Index (PSQI), The PSQI was designed to measure sleep quality and disturbance. A global score > 5 is considered poor sleep quality.	through study completion, an average of 2 year
Changes in resilience	Prospective analyses of resilience using the Brief Resilience Scale (BRS) The BRS is designed to measure the ability to bounce back or recover from stressful events. Higher scores means higher resilience.	through study completion, an average of 2 year

Collaborators and Investigators

• Sponsor: Flemming Bendtsen
• Investigators: Principal Investigator: Flemming Bendtsen, MDSci, Copenhagen University Hospital, Hvidovre

Study record dates

Study Major Dates

• Study Start (Actual): November 28, 2019
• Primary Completion (Estimated): December 31, 2024
• Study Completion (Estimated): March 1, 2025

Study Registration Dates

• First Submitted: October 10, 2019
• First Submitted That Met QC Criteria: October 18, 2019
• First Posted (Actual): October 21, 2019

Study Record Updates

• Last Update Posted (Actual): September 26, 2023
• Last Update Submitted That Met QC Criteria: September 25, 2023
• Last Verified: September 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Diseases; Inflammatory Bowel Diseases; Ulcer; Colitis; Colitis, Ulcerative; Physiological Effects of Drugs; Peripheral Nervous System Agents; Analgesics; Sensory System Agents; Anti-Inflammatory Agents, Non-Steroidal; Analgesics, Non-Narcotic; Anti-Inflammatory Agents; Antirheumatic Agents; Mesalamine
• Other Study ID Numbers: 1337-EASI-trial

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No