Clinical trial NCT02004782: Barretts oEsophageal Resection With Steroid Therapy Trial
Official 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.
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE4
Conditions: Barrett Esophagus
Esophageal Stenosis
Lead sponsor: Western Sydney Local Health District
Sponsor class: OTHER
First posted: 2013-12-09
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 90
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: PREVENTION

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.


Eligibility criteria: 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.

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).

Primary outcomes:
measure: Rate of symptomatic stricture formation
timeFrame: >2 days
Secondary outcomes:
measure: Dilations
timeFrame: Two weeks or more
measure: Dysphagia score
timeFrame: 3, 6 and 12 months
measure: Stricture formation
timeFrame: 3, 6, 12 months
measure: Recurrence
timeFrame: 3, 6 and 12 months
Other outcomes:
measure: Cost
timeFrame: 0-12 months
Locations:
city: Westmead
country: Australia
facility: Westmead Hospital
state: New South Wales
Study officials:
affiliation: Western Sydney Local Health District
name: Michael Bourke
role: PRINCIPAL_INVESTIGATOR
References: