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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02004782




Registration number
NCT02004782
Ethics application status
Date submitted
25/11/2013
Date registered
9/12/2013
Date last updated
3/07/2023

Titles & IDs
Public title
Barretts oEsophageal Resection With Steroid Therapy Trial
Scientific title
Reduction in Symptomatic Oesophageal Stricture Formation Post-two Stage Complete Barrett's Excision for High Grade Dysplasia or Early Adenocarcinoma With Short-term Steroid Therapy: A Randomized, Doubleblind, Placebo-controlled, Multicentre Trial.
Secondary ID [1] 0 0
HREC2013/7/4.5(3702)
Universal Trial Number (UTN)
Trial acronym
BERST
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Barrett Esophagus 0 0
Esophageal Stenosis 0 0
Condition category
Condition code
Oral and Gastrointestinal 0 0 0 0
Other diseases of the mouth, teeth, oesophagus, digestive system including liver and colon
Cancer 0 0 0 0
Oesophageal (gullet)

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Prednisolone
Treatment: Drugs - Placebo Oral Tablet

Active comparator: Prenisolone - Daily prednisolone is taken for 6 weeks, at a dose of 40mg in week 1, 30mg in week 2, 20mg week 3 and 4, 10mg in week 5, and 5mg in week 6. Prednisolone is taken in the morning. Treatment commences the day of the procedure, with the dose taken with a sip of water prior to discharge. The 6-week treatment regimen is given after both the 1st and 2nd stage CBE.

Placebo comparator: Placebo - Daily placebo is taken for 6 weeks, at a dose of 40mg in week 1, 30mg in week 2, 20mg week 3 and 4, 10mg in week 5, and 5mg in week 6. Placebo is taken in the morning. Treatment commences the day of the procedure, with the dose taken with a sip of water prior to discharge. The 6-week treatment regimen is given after both the 1st and 2nd stage CBE.


Treatment: Drugs: Prednisolone
Daily prednisolone is taken for 6 weeks, at a dose of 40mg in week 1, 30mg in week 2, 20mg week 3 and 4, 10mg in week 5, and 5mg in week 6. Prednisolone is taken in the morning. Treatment commences the day of the procedure, with the dose taken with a sip of water prior to discharge. The 6-week treatment regimen is given after both the 1st and 2nd stage CBE.

Treatment: Drugs: Placebo Oral Tablet
Daily placebo is taken for 6 weeks, at a dose of 40mg in week 1, 30mg in week 2, 20mg week 3 and 4, 10mg in week 5, and 5mg in week 6. Placebo is taken in the morning. Treatment commences the day of the procedure, with the dose taken with a sip of water prior to discharge. The 6-week treatment regimen is given after both the 1st and 2nd stage CBE
Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Rate of symptomatic stricture formation
Timepoint [1] 0 0
>2 days
Secondary outcome [1] 0 0
Dilations
Timepoint [1] 0 0
Two weeks or more
Secondary outcome [2] 0 0
Dysphagia score
Timepoint [2] 0 0
3, 6 and 12 months
Secondary outcome [3] 0 0
Stricture formation
Timepoint [3] 0 0
3, 6, 12 months
Secondary outcome [4] 0 0
Recurrence
Timepoint [4] 0 0
3, 6 and 12 months

Eligibility
Key inclusion criteria
1. Histologically confirmed Barretts mucosa with High Grade Dysplasia or early adenocarcinoma (T1a, intramucosal adenocarcinoma).
2. Barretts segment = 30% circumference, =C3 and =M5.
3. The general health condition of the patient permits anaesthesia for endoscopy.
4. Patient is 18 years of age or older.
5. Informed consent is obtained
Minimum age
18 Years
Maximum age
90 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Previous (referral) biopsies show low grade dysplasia only, or invasive adenocarcinoma.
2. Barretts segment <30% circumference, >C3 or >M5.

4. During initial gastroscopy there are highly suspicious areas for submucosal invasive cancer (Kudo pit pattern type V; excavated/depressed type morphology; large smooth or ulcerated nodule). In cases of significant doubt, initial resection is of the highly suspicious area only, and urgent histology processing requested. If submucosal invasion is excluded, the patient is rebooked for 1st stage CBE (60% circumferential resection) and randomization after a 4-6 weeks interval.

4. Presence of a tight peptic oesophageal stricture that impedes safe and effective EMR using the Duette cap.

5. Active malignancy, uncontrolled Diabetes Mellitus, active or untreated major psychiatric disorder, uncontrolled infection, uncontrolled hypertension, uncontrolled or severe congestive cardiac failure, non-correctable coagulopathy (INR>2, or platelet count <60 x 109/L), osteoporosis, recent peptic ulcer disease, moderate-to-severe glaucoma or untreated glaucoma, or pregnancy.

6. Unable to provide informed consent 7. Allergy to compound used in tablet formulation: Microcrystalline cellulose (MCC).

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s


The people analysing the results/data
Intervention assignment
Single group
Other design features
Phase
Phase 4
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Withdrawn
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
1/03/2022
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
1/06/2022
Actual
Sample size
Target
Accrual to date
Final
0
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 0 0
Westmead Hospital - Westmead
Recruitment postcode(s) [1] 0 0
2145 - Westmead

Funding & Sponsors
Primary sponsor type
Other
Name
Professor Michael Bourke
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Barretts mucosa is a premalignant condition of the oesophagus, which can progress to cancer. Oesophageal cancer is aggressive, with a 5 year survival of only \~15%. High risk Barretts mucosa, containing high grade dysplasia or early cancer, can be removed by endoscopic mucosal resection (EMR) during gastroscopy. If patients can be effectively treated by EMR while they have premalignant or early malignant disease, it is a curative procedure.

Currently, the major limitation of Complete Barretts Excision (CBE) by EMR, is scar tissue development in the oesophagus, leading to stricture formation and difficulty swallowing (dysphagia). If a safe and effective method could be found to reduce this risk, the treatment options for early oesophageal cancer would be greatly improved. CBE is performed as a two stage procedure, with 2 gastroscopies 8 weeks apart. In this randomised, doubleblind study, eligible and enrolled patients are randomised after the 1st stage CBE to receive either prednisolone tablets or placebo. Inclusion criteria are patients with short segment (\<3cm circumferential disease) Barretts oesophagus with high grade dysplasia or early cancer. The treatment period is for 6 weeks after both CBE sessions. Prednisolone is given in a reducing dose over the 6 weeks, starting at 40mg daily.

The primary outcome is symptomatic dysphagia development. Endoscopic dilation will be performed as required for dysphagia secondary to symptomatic oesophageal stricture formation persisting for =2 days, or complete dysphagia for any time period. Endoscopic surveillance with biopsies will occur at a 3 month, 6 month then 12 month interval following CBE, to assess for complete removal of Barretts mucosa.

Following two stage CBE, stricture rates without preemptive therapy in noncircumferential, circumferential \<2cm, and circumferential \<3cm disease, are estimated to be 30%, 50% and 70% respectively. The investigators predict a 50% reduction in stricture rate with oral steroid therapy. With a primary analyses of oral steroid versus placebo tested at a 5% level of significance in a two tailed test, 58 patients are needed per group. Allowing for a 5% drop out rate, a total of 126 patients are required. The study will be performed at five Australian Tertiary Hospitals, and the recruitment period is estimated to be 2 years.
Trial website
https://clinicaltrials.gov/study/NCT02004782
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Michael Bourke
Address 0 0
Western Sydney Local Health District
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries



Summary Results

For IPD and results data, please see https://clinicaltrials.gov/study/NCT02004782