Barretts oEsophageal Resection With Steroid Therapy Trial

Phase 4

Withdrawn

• Conditions: Esophageal Stenosis; Barrett Esophagus
• Interventions: Drug: Placebo Oral Tablet; Drug: Prednisolone

• Registration Number: NCT02004782
• Lead Sponsor: Professor Michael Bourke

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2013-11-25
• Study First Submitted QC: 2013-12-03
• Study First Posted: 2013-12-09
• Study Start: 2020-03-09
• Primary Completion: 2020-03-09
• Study Completion: 2020-03-09
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-25
• Last Update Posted: 2025-03-27

Recruitment & Eligibility

• Status: WITHDRAWN
• Sex: All
• Target Recruitment: Not specified

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

Exclusion Criteria

1. Previous (referral) biopsies show low grade dysplasia only, or invasive adenocarcinoma.

2. Barretts segment <30% circumference, >C3 or >M5.

3. 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

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Placebo	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.
Prenisolone	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.

Primary Outcome Measures

Name	Time	Method
Rate of symptomatic stricture formation	>2 days	Rate of symptomatic oesophageal stricture formation.A symptomatic stricture is defined as a stricture leading to the inability to tolerate a soft diet for ≥ 2 days, or the presence of complete dysphagia for any length of time.

Secondary Outcome Measures

Name	Time	Method
Dilations	Two weeks or more	The need for, and number of endoscopic dilations.
Dysphagia score	3, 6 and 12 months	Dysphagia score (DS) at 3, 6 and 12 month surveillance endoscopies. DS: 0 = Normal diet; 1 = Some solid foods; 2 = Semi-solid foods; 3 = Liquids only; 4 = Total dysphagia
Stricture formation	3, 6, 12 months	Endoscopic evidence of stricture formation at 3, 6 and 12 month surveillance endoscopies. No stricture, mild stricture, moderate stricture ('hugs' the gastroscope but the gastroscope can pass), severe stricture (cannot be passed with the gastroscope)
Recurrence	3, 6 and 12 months	Recurrence of Barretts mucosa, defined as the presence of Barretts mucosa endoscopically, or mucosal columnar epithelium with or without intestinal metaplasia on surveillance biopsies. Measured at 3-month surveillance (20 weeks post 1st CBE), 6 month surveillance (46 weeks post 1st CBE), and 12 month surveillance (98 weeks post 1st CBE) endoscopies.

Trial Locations

Locations (1)

Westmead Hospital; 🇦🇺 Westmead, New South Wales, Australia