IBD Neoplasia Surveillance Pilot RCT (IBDDysplasia)

A Randomized, Parallel-Group, Non-Inferiority Trial Comparing Random AND Targeted Biopsies to Targeted Biopsies Alone for Neoplasia Screening in Adult Persons With Colonic Inflammatory Bowel Diseases: A Pilot Study

To determine if random biopsies can be safely eliminated from screening of average risk persons with IBD, the investigators propose to carry out a pilot randomized control trial in which targeted biopsies in combination with random biopsies will be compared to targeted biopsies alone in terms of pre-cancerous lesion capture rate, side-effects and CRC risk. The pilot study will aim to capture 20% of the overall study population in order to evaluate the feasibility of recruiting the needed number of participants in the specified time frame, while maintaining high quality of data collection.

Study Overview

• Status: Completed
• Conditions: Inflammatory Bowel Diseases; Colonic Neoplasms; Dysplasia
• Intervention / Treatment: Diagnostic test: Intervention Group; Diagnostic test: Control Group

Detailed Description

Inflammatory Bowel Disease (IBD), including crohn's disease and ulcerative colitis, is a group of diseases characterized by acute and chronic inflammation of the intestinal tract. Persons with IBD are at an increased risk of developing colorectal cancer (CRC) and require frequent CRC screening with colonoscopy. Current IBD screening guidelines recommend the taking of biopsies of any lesions suspected to be pre-cancerous (targeted biopsies), as well as the taking of 30 to 40 random biopsies throughout the colon. The recommendations for random biopsies are based on historical practice and the theory that they would capture "invisible lesions", but are not supported by strong scientific evidence.

In fact, recent evidence has shown that random biopsies capture a very small number of pre-cancerous lesions and that they capture such lesions only in persons with additional risk factors for CRC. In addition, new colonoscopy practices and technology have made 80-90% of pre-cancerous lesions visible. Random biopsies also carry potential risks for patients, including lower gastrointestinal bleeding and bowel perforation, and substantially increase procedural costs and time.

Hence, there is a strong impetus to conduct a well-powered non-inferiority Randomized Controlled Trial (RCT) on this topic in a Canadian setting. With the support of a pan-Canadian IBD clinical trials alliance (the Canadian IBD Research Consortium (CIRC)), and the high prevalence of IBD in Canada, Canadian investigators are well-positioned to undertake such a trial. Before embarking on a large multi-center trial, a one-year pilot feasibility trial will be conducted to ensure that patients can be enrolled efficiently with excellent protocol compliance. A feasibility trial will also provide a crude estimate of the neoplasia detection rate (primary outcome) among persons with colon IBD (cIBD) in Canada, which will allow refinement of the sample size, recruitment period and budget for a definitive trial. To-date, no well-powered or North American RCTs have evaluated random biopsies as an intervention to guide our estimates for a definitive trial.

• Study Type: Interventional
• Enrollment (Actual): 600
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Edmonton, Alberta, Canada
      • University of Alberta
  • British Columbia
    • Vancouver, British Columbia, Canada
      • St. Paul's Hospital
    • Victoria, British Columbia, Canada
      • Pacific Digestive Health / Royal Jubilee Hospital
  • Manitoba
    • Winnipeg, Manitoba, Canada
      • University of Manitoba, Health Sciences Centre
  • NFLD
    • St. John's, NFLD, Canada, A1B 3V6
      • Eastern Regional Health Authority
  • Nova Scotia
    • Halifax, Nova Scotia, Canada
      • Nova Scotia Health Authority
  • Ontario
    • Hamilton, Ontario, Canada, L8L 8E7
      • Hamilton Health Sciences Corporation
    • London, Ontario, Canada
      • London Health Sciences Centre, University Hospital
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital Research Institute
    • Thunder Bay, Ontario, Canada
      • Thunder Bay Regional Health Sciences Centre
    • Toronto, Ontario, Canada
      • Mount Sinai Hospital
  • Quebec
    • Montreal, Quebec, Canada
      • McGill University Health Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• ≥ 18 years old
• Historical endoscopic/histologic disease extending beyond the rectum in UC or involving ≥ 1/3 of colorectum in CD
• > 50% of colon present, with remaining colon meeting above minimum criteria for disease extent (beyond rectum in UC, ≥1/3 colorectum in CD
• cIBD ≥ 8 years duration (or at any time after diagnosis if a patient also has primary sclerosing cholangitis)

• In symptomatic remission at time of colonoscopy

  • For CD: Harvey-Bradshaw Index < 541
  • For UC or IBDU: Partial Mayo Score ≤ 242
• Major purpose of colonoscopy is neoplasia screening/surveillance
• Undergoing colonoscopy with high-definition white light endoscopy

Exclusion Criteria:

• Persons who cannot or are unwilling to provide informed consent
• Persons with a history of colorectal cancer
• Persons with prior subtotal or total colectomy (> 50% of colon removed)
• Persons undergoing colonoscopy to follow-up on recently diagnosed neoplasia identified within the past year
• Persons undergoing pancolonic chromoendoscopy
• Colon mucosa visibility deemed inadequate for surveillance after washing/suctioning (Boston Bowel Preparation Score of 0 or 1 in any segment)
• Incomplete colonoscopy (unable to reach cecum)
• Moderate-to-severe inflammation (Mayo 2-3) involving ≥ 25% of colorectum or mild inflammation (Mayo 1) involving ≥ 50% of colorectum

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Intervention Group; Participants will undergo standard colonoscopy as part of their routine IBD surveillance. During this colonoscopy targeted biopsies (biopsies of any pre-cancerous lesions observed by the doctor) and/or removal of any polyps will be undertaken.	Diagnostic test: Intervention Group; Standard colonoscopy with targeted biopsies only
Other: Control Group; Participants will undergo standard colonoscopy as part of their routine IBD surveillance. During this colonoscopy both random (approximately 32 to 40) and targeted biopsies (and/or removal of any polyps) will be undertaken.	Diagnostic test: Control Group; Standard colonoscopy with random AND targeted biopsies

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Number of Participants Enrolled	Number of participants enrolled within one year from the overall total required.	1 year
Rate of Protocol Adherence	Rate of protocol adherence of major protocol violations on a per-patient basis.	1 year
Rate of overall neoplasia detection	Overall neoplasia detection rate for the definitive trial.	1 year
Adverse Events occurrence	Occurrence of serious and minor post-procedural adverse events within 2 weeks of procedure.	2 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
Rate of Study Variables	1 year
Rate of Missed 2-Week Post-Procedural Assessment for Complications	2 weeks

Collaborators and Investigators

• Sponsor: Ottawa Hospital Research Institute
• Collaborators: Health Sciences Centre, Winnipeg, Manitoba; University of Alberta; McGill University Health Centre/Research Institute of the McGill University Health Centre; University of Toronto; Hamilton Health Sciences Corporation; Nova Scotia Health Authority; Western University, Canada; MOUNT SINAI HOSPITAL; Providence Health & Services; Eastern Health; Thunder Bay Regional Health Sciences Centre; Royal Jubilee Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 6, 2020
• Primary Completion (Actual): September 20, 2022
• Study Completion (Actual): October 6, 2022

Study Registration Dates

• First Submitted: August 7, 2019
• First Submitted That Met QC Criteria: August 22, 2019
• First Posted (Actual): August 26, 2019

Study Record Updates

• Last Update Posted (Actual): March 31, 2023
• Last Update Submitted That Met QC Criteria: March 30, 2023
• Last Verified: March 1, 2023

More Information

Terms related to this study

• Keywords: Biopsy; Colonoscopy; IBD; Dysplasia
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Gastroenteritis; Colonic Diseases; Intestinal Neoplasms; Colorectal Neoplasms; Inflammatory Bowel Diseases; Intestinal Diseases; Colonic Neoplasms
• Other Study ID Numbers: 20190428-01T

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No