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Barretts oEsophageal Resection With Steroid Therapy Trial (BERST)

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ClinicalTrials.gov Identifier: NCT02004782
Recruitment Status : Not yet recruiting
First Posted : December 9, 2013
Last Update Posted : July 4, 2019
Sponsor:
Information provided by (Responsible Party):
Professor Michael Bourke, Western Sydney Local Health District

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.


Condition or disease Intervention/treatment Phase
Barrett Esophagus Esophageal Stenosis Drug: Prednisolone Drug: Placebo Oral Tablet Phase 4

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 126 participants
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Prevention
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.
Estimated Study Start Date : March 30, 2020
Estimated Primary Completion Date : June 2022
Estimated Study Completion Date : June 2022

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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.
Drug: 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.

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.
Drug: 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




Primary Outcome Measures :
  1. Rate of symptomatic stricture formation [ Time Frame: >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 :
  1. Dilations [ Time Frame: Two weeks or more ]
    The need for, and number of endoscopic dilations.

  2. Dysphagia score [ Time Frame: 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

  3. Stricture formation [ Time Frame: 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)

  4. Recurrence [ Time Frame: 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.


Other Outcome Measures:
  1. Cost [ Time Frame: 0-12 months ]
    The direct medical costs and indirect non-medical costs of production lost will be calculated based on Australian Medical guidelines, and compared between each treatment strategy.



Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 90 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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).


Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02004782


Contacts
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Contact: Rebecca Sonson 0298459779 bec2153@gmail.com
Contact: Michael Bourke 98459779 michael@citywestgastro.com.au

Locations
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Australia, New South Wales
Westmead Hospital Recruiting
Westmead, New South Wales, Australia, 2145
Contact: Rebecca Sonson    98459779    Rebecca.Sonson@health.nsw.gov.au   
Principal Investigator: Michael Bourke, MBBS FRACP         
Sponsors and Collaborators
Professor Michael Bourke
Investigators
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Principal Investigator: Michael Bourke Western Sydney Local Health District

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Responsible Party: Professor Michael Bourke, Professor, Western Sydney Local Health District
ClinicalTrials.gov Identifier: NCT02004782     History of Changes
Other Study ID Numbers: HREC2013/7/4.5(3702)
First Posted: December 9, 2013    Key Record Dates
Last Update Posted: July 4, 2019
Last Verified: July 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
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Barrett Esophagus
Esophageal Stenosis
Precancerous Conditions
Neoplasms
Esophageal Diseases
Gastrointestinal Diseases
Digestive System Diseases
Prednisolone
Methylprednisolone Acetate
Methylprednisolone
Methylprednisolone Hemisuccinate
Prednisolone acetate
Prednisolone hemisuccinate
Prednisolone phosphate
Anti-Inflammatory Agents
Glucocorticoids
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Antiemetics
Autonomic Agents
Peripheral Nervous System Agents
Gastrointestinal Agents
Neuroprotective Agents
Protective Agents