Barrett's oesophagus due to chronic reflux in the gullet Digestive System Barrett's oesophagus
Conditions
Interventions
Please note that the doses of the drugs below were added as of 22/05/2007:
Arm A (Standard Therapy): 20 mg esomeprazole
Arm B (Strong Acid Suppression): 80 mg esomepraz
Sponsors
University of Oxford (UK)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: Inclusion criteria as of 24/08/2016: 1. Patients aged over 18 years 2. Circumferential Barrett’s metaplasia of at least 1 cm in length (=C1M1) or a tongue of Barrett’s metaplasia of at least 2 cm in length (=C0M2) (irrespective of the presence now or historically of histologically proven intestinal metaplasia) 3. Patient?s able to give written consent 4. Patient?s with World Health Organization (WHO) activity profile of 0 or 1 i.e. fully active and self-caring Inclusion criteria from 22/05/2007 to 24/08/2016: 1. Patients aged over 18 years 2. Patient with circumferential Barrett?s Metaplasia at least 1 cm long, and histologically proven intestinal metaplasia in at least one sample 3. Patient?s able to give written consent 4. Patient?s with World Health Organization (WHO) activity profile of 0 or 1 i.e. fully active and self-caring Inclusion criteria provided at time of registration: 1. Male between 40 - 75 years 2. At least 2 cm from the gastro-oesophageal junction of circumferential BM (histologically proven by intestinal metaplasia in at least one sample) 3. Able to give written consent 4. World Health Organization (WHO) activity profile of 0 i.e. fully active and self-caring
Exclusion criteria
Exclusion criteria: Exclusion criteria as of 24/08/2016: 1. Patients with high grade dysplasia or carcinoma at enrolment 2. Medical conditions which would make completing endoscopies or completing the trial difficult, including: 2.1. Frequent transient ischaemic attacks (3 or more) or severe cerebral vascular accident in the previous 6 months (patients answering yes were eligible for the PPI-only (non-aspirin) arms of the trial) 2.2. Severe respiratory disease with arterial oxygen saturation of less than 90% at rest 2.3. Severe ischaemic heart disease (exercise tolerance less than 100 yards or life expectancy 6 times/day 3. Patients with absolute contraindications to PPIs, aspirin or their excipients i.e. allergies, ulcers, renal impairment or use of oral anticoagulants. 4. Pregnant or lactating women will not undergo endoscopy and may be given dispensation to stop drug therapy for a year. This should be discussed with the Trial Office. Exclusion criteria from 22/05/2007 to 24/08/2016: 1. Patients with high grade dysplasia or carcinoma at enrolment; 2. Patients with medical conditions which would make completing endoscopies or the trial difficult to complete including: 2.1. Previous transient ischaemic attacks or cerebral vascular disease 2.2. Severe respiratory disease 2.3. Severe ischaemic heart disease or myocardial infarction in the previous 6 months 2.4. Inflammatory bowel disease 3. Patients who are on continuous aspirin or non-steroidal anti-inflammatories or Cox-2 inhibitors (more than 3 courses/year) 4. Patient?s with absolute contraindications to PPIs, aspirin or their excipients such as allergies, ulcers, renal impairment or use of oral anticoagulants 5. Pregnant or lactating women Exclusion criteria provided at time of registration: 1. High grade dysplasia or carcinoma at enrolment 2. Medical conditions which would make endoscopy or the trial difficult or failure to complete including transient ischaemic attacks or cerebral vascular disease, severe respiratory disease, severe ischaemic heart disease or recent myocardial infarction or inflammatory bowel disease 3. Patients who are on continuous aspirin or non-steroidal drugs (more than 3 courses/year) 4. Absolute contraindications (ulcers) or allergies to PPIs or aspirin such as renal impairment and oral anticoagulants
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary outcome measures as of 24/08/2016: A composite primary endpoint of all-cause mortality and conversion to adenocarcinoma and conversion to high grade dysplasia, assessed after all patients have completed at least 8 years of follow up Primary outcome measures from 22/05/2007 to 24/08/2016: The following will be assessed at 4 and 8 years and four yearly until the end of study: 1. Conversion to adenocarcinoma of the oesophagus 2. Conversion to high grade dysplasia 3. Death by all causes | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary outcome measures as of 24/08/2016: 1. All-cause mortality, assessed after all patients have completed at least 8 years of follow up 2. Conversion to oesophageal adenocarcinoma, assessed after all patients have completed at least 8 years of follow up 3. Conversion to high grade dysplasia, assessed after all patients have completed at least 8 years of follow up 4. Death from oesophageal cancer, assessed after all patients have completed at least 8 years of follow up 5. Cost/oesophageal adenocarcinoma prevented, assessed after all patients have completed at least 8 years of follow up 6. Cost/quality adjusted life year saved, assessed after all patients have completed at least 8 years of follow up 7. Molecular markers to be identified at the end of the trial, assessed after the end of the trial following sample analysis Secondary outcome measures from 20/06/2007 to 24/08/2016: The following will be assessed at 4 and 8 years and four yearly until the end of study: 1. Incidence of oesophagectomy 2. Stage of adenocarcinoma 3. Incidence of ablation therapy 4. Incidence of endoscopic mucosal resection 5. Quality of life, assessed by The Reflux Disease Questionnaire and the Euroqol-5 Dimensions (EQ-5D) Questionnaire 6. Molecular endpoints including genotype and mutational status Secondary outcome measures added as of 22/05/2007: 1. Oesophagectomy 2. Stage of adenocarcinoma 3. Ablation therapy 4. Endoscopic mucosal resection | — |
Countries
United Kingdom
Outcome results
None listed