Know Cancer

forgot password

BRIDE (Barrett's Randomised Intervention for Dysplasia by Endoscopy) - a Feasibility Study

18 Years
85 Years
Not Enrolling
Barrett's Esophagus, Esophageal High-Grade Intraepithelial Neoplasia, Esophageal Cancer Stage I

Thank you

Trial Information

BRIDE (Barrett's Randomised Intervention for Dysplasia by Endoscopy) - a Feasibility Study

The study will comprise 2 parts:

Firstly, randomising up to 100 suitable patients over a 1 year period, identified at the
upper gastrointestinal cancer specialist multidisciplinary team meeting in 6 expert English
centres. Patients will have either high grade dysplasia (HGD) or early cancer in Barrett's
oesophagus (BE) and will be randomised to two curative endoscopic non-surgical therapies
(endoscopic resection [ER] and argon plasma photocoagulation [APC] versus ER and
radiofrequency ablation [RFA]). All techniques are used in current clinical practice, but
have never been directly compared.

Secondly, 2 qualitative studies in which we will examine clinicians' and surgeon's attitudes
towards a trial of oesophageal surgery compared to endoscopic treatment (ER and ablation) by
questionnaire. Qualitative interviews with a purposive sample of patients will explore their
views of randomisation, recruitment and participation to help identify and pre-empt problems
in subsequent planned trials of endoscopic treatments compared to each other and to surgical
removal of all or part of the gullet.

Participants will be randomised to the ER plus RFA or ER plus APC group at enrollment. The
randomisation schedule will be managed by the University of Leicester Clinical Trials Unit,
using a computer generated random assignment.

Randomisation will be stratified for length of Barrett's epithelium (< 5; 5-10; > 10 cm).


Currently available estimates of eradication rates have poor precision, being derived from
small case series. Consequently the sample size has been chosen to allow estimation of the
quantities of interest whilst not exposing too many patients to trial procedures.

10- -15 new cases per million population per year are treated. Each participating centre is
based on an upper gastrointestinal cancer treatment centre serving 1.5- - 2 million people.

Since each centre would expect to see 15- - 20 new patients a year, we aim recruit up to 100
patients over 1 year from 6 UK centres.


ER, RFA and APC are all techniques used in current practice, with which all investigators
are familiar. We will ensure that all investigators are using the same techniques and that
histological assessment is scrutinised by an an external expert pathology panel (see quality
control below).

Best practice is to perform ER of all visible lesions. We will therefore aim for complete
resection of all visible lesions initially and ablate residual flat Barrett's mucosa at
subsequent treatment sessions (at 2 monthly intervals up to 8 months after the initial
treatment by ER).

The treatment phase of the trial terminates at 8 months. At T= 12 months, diagnostic high
resolution endoscopy is performed with targeted biopsies of any abnormal areas as well as 4
quadrant biopsies at 2 cm intervals of the area containing or previously containing the BE.
The biopsies are in order to identify 'buried' Barrett's glands under the new squamous
epithelium. The clinical endpoint is at 1 year when recurrent or persistent HGD or cancer
will be assessed. Any residual BE (not containing HGD or cancer) will be assessed and


A purposive sub-sample of patients (sampling strategy designed to include a wide range of
views and experiences, including patients from each centre) will be interviewed by telephone
after being invited to take part in the feasibility trial, using a topic guide (developed
collaboratively with lay representatives, with an emphasis on encouraging patients to
describe their own perspectives freely - a preliminary topic guide has been developed and is
included with this application), exploring views on being invited to participate in research
in which they are randomised to different treatment options. The interview would also invite
views on conducting a trial of endotherapy versus surgery. Interviews will be audio-recorded
with separate consent and transcribed verbatim by transcribers working to professional
standards of confidentiality.

Analysis of Qualitative Data

Analysis of the interview transcripts will be based on the constant comparative approach and
managed by NVivo software. The findings will thus include a set of issues that are important
from a patient perspective, that can help/hinder recruitment and retention, to inform
subsequent trials.

Surgeon/clinician Questionnaires

A purposive sample of surgeons and clinicians at expert centres will receive questionnaires
to explore views to endotherapy and surgery for the treatment of Barrett's oesophagus with
HGD or early cancer and on the proposed trials (including 'free text' options inviting views
on randomization to a trial comparing surgery to endoscopic treatment). Questionnaires will
be distributed to up to 100 oesophagogastric surgeons and clinicians (lead MDT
gastroenterologists or expert endoscopists) from the participating centres and other centres
in the UK as advised by our surgical lead. The questionnaires will be administered by e
mail. A second e mail will follow after a month in the case of non-response, but those who
chose not to respond thereafter will not be further contacted.

Quality of life assessments and healthcare cost assessment

Quality of Life will be assessed at baseline and at the 6 and 12 months visits, using the
EORTC Quality of Life Questionnaire version 3.0 (EORTC QLQ-C30) and module QLQ-OES18 to
assess specific relevant aspects of quality of life related to oesophageal disease. General
quality of life will also be assessed using EQ-5D. Additional data on healthcare utilisation
will be collected at baseline, 6 and 12 months using a questionnaire we have developed which
patients will be asked to complete at these scheduled visits for endoscopy.

The perspective of the economic analysis will be that of the NHS and personal social
service. Costs to be obtained will include the costs of endoscopic treatment and continued
endoscopic surveillance in both groups, as well as any additional intervention after the
initial 8- month therapeutic phase of the trial. The costs of any salvage treatment at any
stage will be included. We will test the validity and feasibility of administering the
economic evaluation questionnaire (patient healthcare utilisation questionnaire and EQ-5D),
examining the response rate achieved and levels of missing data. EORTC QLQ- C30 will also be
tested to directly estimate QALYs using EORTC- 8D. Both EQ-5D and EORTC will be used to
obtain the appropriate information for cost per QALY analysis in future economic evaluation.
The economic analysis will inform sample size calculation and other necessary information to
calculate the cost savings for future economic evaluation.

Inclusion Criteria


- Histology: high grade dysplasia (HGD) or early cancer with a maximum depth of
invasion on endoscopic resection (ER) of T1m3

- Endoscopic ultrasound if any endoscopically visible abnormality: negative for T2
invasion or greater, and for suspicious lymph nodes.

- CT scan (thorax & top 1/3 of abdomen): negative for evidence of locally advanced or
metastatic disease (done at the discretion of the multidisciplinary team, for
invasive cancer only - T1m disease); PET-CT will not usually be required but may be
carried out if indicated at the discretion of the multidisciplinary team.

- Suitability for trial agreed at local upper gastrointestinal cancer multidisciplinary
team (MDT).

- Able to give informed consent

- Able (if applicable) to discontinue Clopidogrel for 7 days before & after endotherapy
i.e. 14 days in total.

- Able (if applicable) to discontinue Warfarin with or without a bridging plan using
low molecular weight heparin. The Warfarin can be restarted 1-7 days after
endotherapy according to the local endoscopist's usual clinical practice.


- Histology: depth of invasion beyond muscularis mucosae histologically (> T1m), poorly
differentiated T1m cancers or lymphatic invasion or vascular invasion.

- Short tongues (<2 cm) of Barrett's epithelium that could be completely removed by
Endoscopic Resection

- No localised endoscopically identifiable abnormality by high definition endoscopy
(with or without magnification or chromo-endoscopic techniques)

- Prior oesophageal endoscopic therapy: e.g. Photodynamic Therapy, Endoscopic
resection, prior ablation by other techniques such as argon ablation.

- Existing symptomatic stricture or one caused by the study diagnostic ER unless this
can be dilated and the patient is then judged to be suitable for endoscopic treatment
by the expert endoscopist.

- History of: radiation to mediastinum, oesophageal surgery (except fundoplication
without complication), oesophageal varices or coagulopathy.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Health Services Research

Outcome Measure:

Recruitment rate and retention

Outcome Description:

BRIDE is a feasibility study randomising up to 100 patients with high grade dysplasia or early cancer in Barrett's oesophagus to two curative endoscopic non-surgical therapies (endoscopic resection and argon plasma photocoagulation versus endoscopic resection and radiofrequency ablation). Primary outcome measures at 12 months after baseline are: - Recruitment rate and retention The primary aim is to gain information that will enable realistic estimation of recruitment/retention rates in order to inform a fully powered trial (BRIDE 2) comparing the 2 endoscopic treatment techniques.

Outcome Time Frame:

12 months

Safety Issue:


Principal Investigator

John S de Caestecker, MD FRCP

Investigator Role:

Principal Investigator

Investigator Affiliation:

University Hospitals, Leicester


United Kingdom: Research Ethics Committee

Study ID:

CLRN 119238



Start Date:

February 2013

Completion Date:

November 2015

Related Keywords:

  • Barrett's Esophagus
  • Esophageal High-Grade Intraepithelial Neoplasia
  • Esophageal Cancer Stage I
  • Barrett Esophagus
  • Neoplasms
  • Esophageal Diseases
  • Esophageal Neoplasms
  • Carcinoma in Situ